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Sample records for low-grade mucosa-associated lymphoid

  1. Therapy of gastric mucosa associated lymphoid tissue lymphoma

    PubMed Central

    Morgner, Andrea; Schmelz, Renate; Thiede, Christian; Stolte, Manfred; Miehlke, Stephan

    2007-01-01

    Gastric mucosa associated lymphoid tissue (MALT) lymphoma has recently been incorporated into the World Health Organization (WHO) lymphoma classification, termed as extranodal marginal zone B-cell lymphoma of MALT-type. In about 90% of cases this lymphoma is associated with H pylori infection which has been clearly shown to play a causative role in lymphomagenesis. Although much knowledge has been gained in defining the clinical features, natural history, pathology, and molecular genetics of the disease in the last decade, the optimal treatment approach for gastric MALT lymphomas, especially locally advanced cases, is still evolving. In this review we focus on data for the therapeutic, stage dependent management of gastric MALT lymphoma. Hence, the role of eradication therapy, surgery, chemotherapy and radiotherapy is critically analyzed. Based on these data, we suggest a therapeutic algorithm that might help to better stratify patients for optimal treatment success. PMID:17659705

  2. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings.

    PubMed

    Law, T T; Tong, Daniel; Wong, Sam W H; Chan, S Y; Law, Simon

    2015-04-01

    Gastric mucosa-associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pylori-eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosa-associated lymphoid tissue lymphoma and its management are reviewed. PMID:25904569

  3. Duodenal Mucosa-Associated Lymphoid Tissue Lymphomas: Two Cases and the Evaluation of Endoscopic Ultrasonography

    PubMed Central

    Kim, Su Jin; Choi, Choel Woong; Ha, Jong Kun; Hong, Young Mi; Park, Jin Hyun; Park, Soo Bum; Kang, Dae Hwan

    2013-01-01

    Mucosa-associated lymphoid tissue lymphoma mainly arises in the stomach, with fewer than 30% arising in the small intestine. We describe here two cases of primary duodenal mucosa-associated lymphoid tissue lymphoma which were evaluated by endoscopic ultrasonography. A 52-year-old man underwent endoscopy due to abdominal pain, which demonstrated a depressed lesion on duodenal bulb. Endoscopic ultrasonographic finding was hypoechoic lesion invading the submucosa. The other case was a previously healthy 51-year-old man. Endoscopy showed a whitish granular lesion on duodenum third portion. Endoscopic ultrasonography image was similar to the first case, whereas abdominal computed tomography revealed enlargement of multiple lymph nodes. The first case was treated with eradication of Helicobacter pylori, after which the mucosal change and endoscopic ultrasound finding were normalized in 7 months. The second case was treated with cyclophosphamide, vincristine, prednisolone, and rituximab every 3 weeks. After 6 courses of chemotherapy, the patient achieved complete remission. PMID:24143321

  4. Sensitive detection of PrPCWD in rectoanal mucosa-associated lymphoid tissue from preclinical white-tailed deer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in four white-tailed deer test populations: from Wisconsin, a sample of free-ranging deer and a captive herd; and from Saskatchewan, Canada, two captive herds. Th...

  5. Ileal mucosa-associated lymphoid tissue lymphoma presenting with small bowel obstruction: a case report.

    PubMed

    Kinkade, Zoe; Esan, Olukemi A; Rosado, Flavia G; Craig, Michael; Vos, Jeffrey A

    2015-01-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT Lymphoma) of the gastrointestinal tract commonly involves the stomach in the setting of concurrent Helicobacter pylori (H. pylori) infection. Primary ileal MALT lymphoma is rare, and has not been associated with a specific infectious disease. We report a case of a 58-year-old man who presented to the emergency department with constipation and abdominal distension, and signs of an obstructing mass on computed tomography scan. A small bowel resection was performed which revealed an 8cm saccular dilatation with thickened bowel wall and subjacent thickened tan-yellow tissue extending into the mesentery. Histologically, there was a diffuse lymphoid infiltrate consisting of small atypical cells with monocytoid features. These cells were CD20-positive B-lymphocytes that co-expressed BCL-2 and were negative for CD5, CD10, CD43, and cyclin D1 on immunohistochemical studies. Kappa-restricted plasma cells were also identified by in situ hybridization. The overall proliferation index was low with Ki-67 immunoreactivity in approximately 10% of cells. No areas suspicious for large cell or high grade transformation were identified. The pathologic findings were diagnostic of an extranodal marginal zone lymphoma involving the ileum, with early involvement of mesenteric lymph nodes. Small hypermetabolic right mesenteric and bilateral hilar lymph nodes were identified by imaging. The bone marrow biopsy showed no evidence of involvement by lymphoma. The patient was clinically considered advanced stage and opted for therapy with rituximab infusions. After six months of therapy, follow-up radiologic studies demonstrated significant decrease in size of the mesenteric lymph nodes. PMID:26178711

  6. Occult pulmonary mucosa-associated lymphoid tissue lymphoma presenting as catastrophic antiphospholipid antibody syndrome

    PubMed Central

    REGUNATH, HARIHARAN; SHORTRIDGE, JAMES; RAZA, SHAHZAD; NISTALA, PUJA; HUFFMAN, BRANDON M.; WANG, MICHAEL X.; XIANG, DONG

    2013-01-01

    Catastrophic antiphospholipid antibody syndrome (CAPS) is characterized by fulminant thrombosis of the arterial and venous beds of multiple organ systems over a relatively short period of time and with a high mortality rate. Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung has never been reported as a causative or precipitating factor for CAPS in the CAPS registry database. The present study describes a rare case of pulmonary MALT lymphoma of the lung that presented as CAPS. A 19-year-old Hispanic female presented with shortness of breath and abdominal pain. Computed tomography (CT) scans of the chest and abdomen revealed multiple portal vein thromboses and bilateral pulmonary nodules. Within one week of presentation, the patient developed a straight sinus thrombosis and upper extremity deep vein thrombosis, which led to shortness of breath. A biopsy of the lung nodule revealed MALT lymphoma. The present case illustrates a rarely reported pulmonary MALT lymphoma presenting as CAPS in a young female. The patient was successfully treated with 90 mg/m2 bendamustine on days one and two and rituximab 375 mg/m2 on day one of each 28-day cycle. Complete remission of the lung nodules was observed following three cycles of treatment, as visualized by positron emission tomography (PET)/CT scan. Fondaparinux was identified as a feasible anticoagulation drug of choice for this case. At seven months post-treatment, the patient continues to be stable with no further evidence of thrombosis and is currently undergoing rituximab maintenance therapy every six months for two years. A repeat lupus anticoagulant antibody assay turned and remained negative during the clinical follow-up period. A prompt diagnosis and early aggressive treatment is potentially curative and may dramatically decrease the mortality risk. Future studies should explore the role of rituximab in the management of CAPS-associated B-cell lymphoid malignancies. PMID:24179505

  7. Stage IV intramucosal gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type.

    PubMed

    Ohtaka, Masahiko; Sato, Tadashi; Kobayashi, Shouji; Sueki, Ryouta; Yamaguchi, Tatsuya; Uetake, Tomoyoshi; Ohtsuka, Hiroyuki; Iwao, Noriaki; Kirito, Keita; Enomoto, Nobuyuki

    2013-04-01

    A 45-year-old woman with no symptoms underwent upper gastrointestinal endoscopy. A discolored area was noted at the greater curvature of the gastric upper body. Endoscopic ultrasonography demonstrated thickening of the second sonographic layer indicating that the depth of invasion was confined to the mucosa. A urea breath test and anti-Helicobacter pylori antibody test were negative. A computed tomography scan showed a consolidation at the right lung. Gastric biopsy and transbronchial lung biopsy (TBLB) demonstrated a monotonous proliferation of atypical small lymphocytes. A diagnosis of gastric marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) was made. The clinical stage was stage IV. A genetic analysis showed rearrangement of the joining region of the immunoglobulin heavy chain gene and identical clones in both lesions. An API2-MALT1 fusion gene was detected in the gastric lesion. After H. pylori eradication treatment, combination treatment with rituximab plus CHOP (R-CHOP) was performed; 6 months later an endoscopy revealed complete disappearance of the lesion. Multiple gastric biopsies showed no infiltrating atypical lymphocytes. Similarly, the lesion in the lung showed complete remission (CR) on CT and TBLB. This report shows that a gastric MALT lymphoma located in the mucosa and disseminated to the lung maintained CR by R-CHOP. PMID:26181449

  8. A case of spontaneous regression of pulmonary mucosa-associated lymphoid tissue (MALT) type lymphoma with Sjgren's syndrome treated with methotrexate for rheumatoid arthritis

    PubMed Central

    Yasui, Hideki; Nakamura, Yutaro; Hasegawa, Hirotsugu; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Inui, Naoki; Fukuoka, Junya; Suda, Takafumi

    2015-01-01

    A 72-year-old man who had suffered from rheumatoid arthritis (RA) and Sjgren's syndrome (Sjs) since he was 66 years of age had been treated with methotrexate (MTX) for six years. He presented with a cough, sputum and dyspnea on exertion, and computed tomography findings showed multiple ground-glass opacities in both of his lungs. A biopsy of the lungs revealed low-grade mucosa-associated lymphoid tissue (MALT) type B-cell non-Hodgkin's lymphoma. Spontaneous complete remission of the lymphoma was achieved six months after withdrawing immune suppression with MTX. To our knowledge, no previous cases of spontaneous regression of pulmonary MALT-type lymphoma with Sjs treated with MTX for RA have been reported. Patients on MTX who are being treated for RA should be carefully monitored, especially when they have been diagnosed with coexistent Sjs. PMID:26236588

  9. Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review.

    PubMed

    Asano, Naoki; Iijima, Katsunori; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

    2015-07-14

    Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-?B) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-?B activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status. PMID:26185372

  10. Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

    SciTech Connect

    Hata, Masaharu; Omura, Motoko; Koike, Izumi; Tomita, Naoto; Iijima, Yasuhito; Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko; Ogino, Ichiro; Inoue, Tomio

    2011-12-01

    Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I{sub E}A in 29 patients and stage II{sub E}A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

  11. Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report

    PubMed Central

    Matsuda, Ikuo; Watanabe, Takahiro; Enomoto, Yukie; Takatsuka, Yuichi; Miyoshi, Yasuo; Hirota, Seiichi

    2014-01-01

    Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer. PMID:25400790

  12. Diagnosis of preclinical CWD in farmed white-tailed deer in Canada by the immunohistochemical examination of recto-anal mucosa- associated lymphoid tissue (RAMALT)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in two white-tailed deer farms from Saskatchewan, Canada. The apparent prevalence of disease in these two farms was 21% and 31%. None of these deer were demonstra...

  13. Prevalence of Achromobacter xylosoxidans in pulmonary mucosa-associated lymphoid tissue lymphoma in different regions of Europe.

    PubMed

    Adam, Patrick; Czapiewski, Piotr; Colak, Seba; Kosmidis, Perikles; Tousseyn, Thomas; Sagaert, Xavier; Boudova, Ludmila; Oko?, Krzysztof; Morresi-Hauf, Alicia; Agostinelli, Claudio; Pileri, Stefano; Pruneri, Giancarlo; Martinelli, Giovanni; Du, Ming-Qing; Fend, Falko

    2014-03-01

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies. PMID:24372375

  14. Amyloid deposition in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: A clinicopathologic study of 5 cases.

    PubMed

    Zhang, Qi; Pocrnich, Cady; Kurian, Annie; Hahn, Angelika F; Howlett, Christopher; Shepherd, Jessica; Rizkalla, Kamilia

    2016-03-01

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common subtype of marginal zone lymphoma (MZL), with stomach being the most frequent primary site, followed by salivary gland, lung and ocular adnexa. Although clinically indolent, MALT lymphoma has the potential of local recurrence and systemic spread. Amyloid deposition is a very unusual complication of MALT lymphoma. In this study, we report clinicopathologic features of 5 cases of MALT lymphomas with associated amyloid deposits. One case showed amyloid deposits in the primary lesion; the other four cases showed amyloid deposits only in recurrences. Previous studies suggest that the amyloid deposits do not implicate worse prognosis. In our study, although amyloid deposits were focal and organ confined, one patient had extensive deposits of amyloid in the large bowel wall leading to bowel perforation and another patient developed significant peripheral neuropathy due to amyloid deposits in the brachial plexus. In conclusion, amyloid deposits in MALT lymphomas are rare and organ/tumour confined. However, complications can be critical and cause considerable morbidity. Therefore, pathologists should be aware of the association between MALT lymphoma and amyloid deposition, and clinical follow up is warranted. PMID:26847730

  15. Characterization of elongated Helicobacter pylori isolated from a patient with gastric-mucosa-associated lymphoid-tissue lymphoma.

    PubMed

    Toyokawa, Tatsuya; Yokota, Kenji; Mizuno, Motowo; Fujinami, Yoshihito; Takenaka, Ryuta; Okada, Hiroyuki; Hayashi, Shunji; Hirai, Yoshikazu; Oguma, Keiji; Shiratori, Yasushi

    2004-03-01

    To date, two Helicobacter species, Helicobacter pylori and 'Helicobacter heilmannii' (formerly named 'Gastrospirillum hominis'), have been identified from the human stomach. In this study, we observed non-H. pylori-shaped bacteria in gastric tissue sections and successfully isolated them by cultivation. Elongated bacteria were isolated from a patient with gastric-mucosa-associated lymphoid-tissue lymphoma who had been diagnosed as H. pylori-negative by culture, rapid urease test and histopathology in another hospital. The bacteria were grown only on chocolate agar in a CO2 incubator, appeared more than 10 microm long in histological sections, formed small colonies and showed poor growth in a brain heart infusion broth; these characteristics apparently differed from common clinical isolates of H. pylori. However, the bacteria were identified as H. pylori by PCR of the urease gene, 16S rDNA sequencing, protein profile and antigenicity examined by anti-H. pylori polyclonal antibody. These observations suggest that the H. pylori strain identified in this study may contribute to the development of gastroduodenal diseases in cases judged as H. pylori-negative by ordinary methods. PMID:14970245

  16. Mixed large cell neuroendocrine carcinoma and mucosa-associated lymphoid tissue lymphoma of the lung: A case report

    PubMed Central

    MATSUMOTO, TAKESHI; IMAI, YUKIHIRO; KOSAKA, YASUHIRO; SHINTANI, TAKASHI; TOMII, KEISUKE

    2015-01-01

    In the present study, a 79-year-old male was referred to Kobe City Medical Center General Hospital due to an abnormal shadow that was revealed on a chest X-ray. The patient possessed a five-year history of consolidation in the right lower lobe, which was diagnosed as chronic aspiration pneumonia and followed up. However, the abnormal shadow adjacent to the pleura gradually increased in size and a novel mass appeared in the right lower lobe that rapidly increased in size. A repeat biopsy revealed a combination of large cell neuroendocrine carcinoma with a clinical tumor-node-metastasis (cTNM) stage of cT2bN2M0 (stage 3A) and mucosa-associated lymphoid tissue lymphoma at Ann Arbor stage 1E. Chemoradiotherapy markedly affected the lesion and the size of the mass was significantly reduced subsequent to four cycles of chemotherapy, which was considered to be a near complete response. The present study reports an extremely rare combination of tumors. The disease course was followed over a period of six years, which included the onset of disease, and the present case may therefore be valuable in clarifying the mechanism of lung cancer development. PMID:26137014

  17. Primary Sjögren's syndrome initially presenting as submandibular mucosa-associated lymphoid tissue lymphoma: A case report

    PubMed Central

    CHEN, LIANG-YU; TSAI, MING-HSUI; TSAI, LI-TAI; LU, HSIN-MAN; JAN, CHIA-ING

    2016-01-01

    The present study reports the case of a 24-year-old female affected with primary Sjögren's syndrome (pSS), who presented with mucosa-associated lymphoid tissue (MALT) lymphoma of the submandibular gland. Reports of such cases, particularly in young patients, are very rare. The patient, who presented no oral or ocular symptoms prior to the development of the mass, underwent surgical ablation of the gland, and MALT lymphoma was diagnosed by histopathology. Since MALT lymphoma in the submandibular gland is rarely observed in otherwise healthy young females, a rheumatologist and an oncologist were consulted. Following a number of immunological tests, the results of the Schirmer's and Saxon tests were negative. However, the antinuclear antibody test revealed a speckled appearance, and there was also strong positivity for the serological markers of Sjögren's syndrome. Consequently, pSS was diagnosed, despite the fact that the patient did not fulfill all the diagnostic criteria for the disease. Therefore, MALT lymphoma in a single salivary gland should be used as a differential diagnosis for Sjögren's syndrome in young asymptomatic patients. Additionally, a multidisciplinary team is required for the treatment and management of these patients. PMID:26893669

  18. [A Case of Concurrent Primary Gastric Malignant T-Cell Lymphoma and Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma].

    PubMed

    Hashimoto, Tadayoshi; Tamura, Shigeyuki; Takeno, Atsushi; Taniguchi, Hirokazu; Ishida, Tomo; Sato, Yasufumi; Morimoto, Yoshihiro; Kusama, Hiroki; Matsushita, Katsunori; Kimura, Kei; Katsura, Yoshiteru; Nitta, Kanae; Ohmura, Yoshiaki; Kagawa, Yoshinori; Okishiro, Masatsugu; Sakisaka, Hideki; Egawa, Chiyomi; Takeda, Yutaka; Kato, Takeshi

    2015-11-01

    A 71-year-old man was admitted to our hospital for epigastric pain. Upper gastrointestinal endoscopy revealed a type 2- like ulcerative lesion in the posterior wall of the upper and middle part of the stomach. Endoscopic biopsies showed malignant T-cell lymphoma histologically. A chest CT scan revealed a nodule in the apex of right lung, suggestive of primary lung cancer. A total gastrectomy with D2 lymphadenectomy and distal pancreatectomy with splenectomy was performed. Seventy-three days after surgery, the patient developed a lung abscess in the middle lobe of the right lung. A wedge-shaped resection of the upper lobe and total resection of the middle lobe of the right lung was performed. Histological examination revealed a primary pulmonary mucosa-associated lymphoid tissue lymphoma in the upper lobe of right lung and an abscess caused by Pseudomonas aeruginosa in the middle lobe of the right lung. Twelve months after surgery the man died of suffocation because of aspiration due to esophageal stenosis caused by progression of metastasis of the paraesophageal lymph node. PMID:26805184

  19. C-MYC overexpression predicts aggressive transformation and a poor outcome in mucosa-associated lymphoid tissue lymphomas.

    PubMed

    Huang, Wenting; Guo, Lei; Liu, Hongyan; Zheng, Bo; Ying, Jianming; Lv, Ning

    2014-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common, indolent B-cell lymphoma. MALT lymphoma with large tumor cells (LTCs) is believed to have the potential to transform to aggressive diffuse large B-cell lymphoma (DLBCL) which may have a poor prognosis. C-MYC is a transcription factor. Its translocation and overexpression predicts an inferior prognosis and poor response to therapy in cases of DLBCL. In the current study, C-MYC expression was detected in MALT lymphomas, and its relationship to the occurrence of LTCs, clinicopathological parameters and prognosis was assessed. A total of 69 cases were enrolled in the study, including 42 cases of MALT lymphoma without LTCs, 20 cases of MALT lymphoma with LTCs and 7 cases of DLBCL with a MALT lymphoma component (DLBCL+MALT). Immunohistochemistry and fluorescent in situ hybridization analyses were performed. In total, 15/42 (35.7%) cases were nuclear positive for C-MYC expression in the group without LTCs, whereas 15/20 (75.0%) and 4/7 (57.1%) cases were positive in the group with LTCs and in the group with DLBCL+MALT, respectively (P=0.004). Univariate and multivariate analysis were used to determine the correlations of C-MYC expression and clinicopathological parameters with overall survival (OS). C-MYC expression, Ann Arbor stage, LDH level and IPI were considerably associated with OS according to the univariate analysis. However, only C-MYC expression ? 20% showed a statistical significance in the multivariate analysis (HR=20.604, 95% CI: 1.909-222.412, P=0.013). Therefore, C-MYC overexpression may play an important role in aggressive transformation and is an independent prognostic factor in MALT lymphoma. PMID:25337204

  20. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

    SciTech Connect

    Anacak, Yavuz; Miller, Robert C.; Constantinou, Nikos; Mamusa, Angela M.; Epelbaum, Ron; Li Yexiong; Calduch, Anna Lucas; Kowalczyk, Anna; Weber, Damien C.; Kadish, Sidney P.; Poortmans, Philip; Kamer, Serra; Ozsahin, Mahmut

    2012-01-01

    Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

  1. Evaluation of the clinical characteristics, management, and prognosis of 103 patients with gastric mucosa-associated lymphoid tissue lymphoma

    PubMed Central

    LI, XIAOWU; WANG, XIANG; ZHAN, ZHONGLI; ZHANG, LIANYU; SUN, BAOCHUN; ZHANG, YIZHUO

    2016-01-01

    The diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is difficult owing to its non-specific symptoms and various endoscopic findings. Treatments such as radiotherapy (RT) for localized and chemotherapy (CT) for advanced stages of the disease are employed. The aim of the present study was to examine the clinical characteristics and prognostic factors of Helicobacter pylori (H. pylori) eradication (HPE) in patients with gastric MALT lymphoma. The medical records of 103 patients with gastric MALT lymphoma for the period 2001–2013, were analyzed. The 103 median age of the patients was 53 years and the male to female ratio was 1:1. Serum lactate dehydrogenase and β2-microglobulin were within normal range. Macroscopically, the most commonly involved site was the antrum, followed by the corpus and fundus. A total of 97 patients (94%) tested positive for H. pylori. Forty patients (39%) had stage I, 35 patients (35%) had local or distant nodal involvement, 20 of 103 patients had stage IIIE (19%) and 8 of 103 patients had stage IV (7%) disease. Complete remission, after HPE, was achieved in 54 of the 69 patients (78%) that were H. pylori-positive and in 2 of the 4 patients (50%) that were H. pylori-negative. HPE had a superior trend in the H. pylori-positive patients although no significant difference was identified in the two groups (p=0.194). In patients with advanced disease, the 5-year progression-free survival (PFS) and overall survival (OS) estimates were significantly improoved for patients receiving HPE with CT or RT than those receiving CT or RT (p=0.046 and 0.035, respectively). The multivariate analysis revealed that, the advanced stages were independently associated with shorter PFS, and the modified-International Prognostic Index (m-IPI) (≥2) was associated with shorter OS. In conclusion, gastric MALT lymphoma had a favorable outcome with a high OS rate. HPE was an effective treatment for gastric MALT lymphoma. The patients with advanced stages and m-IPI (≥2) had a much worse prognosis.

  2. Concurrent Gastric and Pulmonary Mucosa-Associated Lymphoid Tissue Lymphomas with Pre-Existing Intrinsic Chronic Inflammation: A Case Report and a Review of the Literature

    PubMed Central

    Oh, Sooyeon; Kim, Nayoung; Oh, Dong Hyun; Bang, Soo-Mee; Choi, Yoon Jin; Lee, Ju Yub; Lee, Kyung Won; Yoon, Ho Il; Yang, Hee Chul; Paik, Jin Ho; Lee, Dong Ho; Jung, Hyun Chae

    2015-01-01

    Herein, we report a rare case of concurrent gastric and pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas. A 65-year-old man who had been diagnosed with Helicobacter pylori-positive gastric MALT lymphoma received eradication therapy and achieved complete remission. During follow-up, he developed de novo pulmonary MALT lymphoma as a sequela of pulmonary tuberculosis, accompanied by recurrent gastric MALT lymphoma. Polymerase chain reaction (PCR) products of the CDR3 region of the immunoglobulin heavy chain gene showed an overall polyclonal pattern with bands at 400 base pairs (bp) and 200 bp predominant in the pulmonary tissue, as well as two distinctive bands in the gastric tissue at 400 bp and 200 bp. This case suggests that multiorgan lymphomas are more likely to be independent from each other when they are far apart, involve different organ systems, and have independent precipitating factors. PMID:25918263

  3. Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

    PubMed

    Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

    2013-12-01

    Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

  4. Co-Occurrence of Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Long-Standing Hashimoto Thyroiditis

    PubMed Central

    Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

    2013-01-01

    Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

  5. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue-from (auto)antigen driven selection to the activation of NF-?B signaling.

    PubMed

    Zhang, YiAn; Wei, Zheng; Li, Jing; Liu, Peng

    2015-12-01

    Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra- or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-?B signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future. PMID:26612043

  6. Low-Dose Radiation Treatment in Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma: A Plausible Approach? A Single-Institution Experience in 10 Patients

    SciTech Connect

    Girinsky, Theodore; Paumier, Amaury; Ferme, Christophe; Hanna, Colette; Ribrag, Vincent; Leroy-Ladurie, Francois; Ghalibafian, Mithra

    2012-07-01

    Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 Multiplication-Sign 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.

  7. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  8. Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

    SciTech Connect

    Son, Seok Hyun; Choi, Byung Ock; Kim, Gi Won; Yang, Suk Woo; Hong, Young Seon; Choi, Ihl Bohng; Kim, Yeon Sil

    2010-05-01

    Purpose: To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). Methods and Materials: We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8-2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1-113.6 months). Results: Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. Conclusion: Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

  9. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    SciTech Connect

    Olszewski, Adam J. Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  10. Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

    SciTech Connect

    Hashimoto, Naoki; Sasaki, Ryohei; Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo; Azumi, Atsushi; Matsui, Toshimitsu; Sugimura, Kazuro

    2012-03-15

    Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

  11. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    SciTech Connect

    Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  12. [Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report].

    PubMed

    Hatano, Koji; Sato, Mototaka; Tsujimoto, Yuichi; Takada, Tsuyoshi; Honda, Masato; Matsumiya, Kiyomi; Fujioka, Hideki; Oka, Kazuhisa; Tsujimoto, Masahiko

    2007-01-01

    We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression. PMID:17310771

  13. Eleven-year experience of low grade lymphoma in Korea (based on REAL classification).

    PubMed

    Hahn, Jee Sook; Kim, Yong Soo; Lee, Yong Chan; Yang, Woo Ick; Lee, Sang Yeal; Suh, Chang Ok

    2003-10-30

    Low grade lymphomas are malignancies of predominantly small lymphocytes that typically have long median survival periods due to low proliferative rates. It is considered an indolent disease, but patients with low grade lymphoma can almost never be cured with conventional treatment. New low- grade lymphoma entities have been classified by the International Lymphoma Study Group (ILSG) and are also categorized into the Revised European American Lymphoma (REAL) classification. The REAL classification utilizes a multiparameter definition of clinico-pathologic and biologic entities. According to this classification, we investigated the incidence, various clinical characteristics, treatment outcome and prognostic factors of low grade lymphoma. Many clinical characteristics of low grade lymphoma in Korea differed from those of Western countries, especially in the incidence, therapeutic outcome and prognostic factors. In Korea, although the general incidence of low grade lymphoma is relatively low, the relative number of mucosa-associated lymphoid tissue lymphoma (MALToma) is very high, and the overall survival rate is better than that reported of Western countries. Thus, further investigation on treatment outcome and prognosis of low grade lymphoma entities, other than mucosa- associated lymphoid tissue lymphoma, are warranted. PMID:14584090

  14. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    PubMed

    Prez de Diego, Rebeca; Snchez-Ramn, Silvia; Lpez-Collazo, Eduardo; Martnez-Barricarte, Rubn; Cubillos-Zapata, Carolina; Ferreira Cerdn, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor ?B in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of eachof the components of the CBM complex to human immunity. PMID:26277595

  15. Primary Pulmonary Lymphoid Lesions: Radiologic and Pathologic Findings.

    PubMed

    Sirajuddin, Arlene; Raparia, Kirtee; Lewis, Vanessa A; Franks, Teri J; Dhand, Sabeen; Galvin, Jeffrey R; White, Charles S

    2016-01-01

    The pulmonary lymphoid system is complex and is composed of two compartments: the pulmonary lymphatics and the bronchus-associated lymphoid tissue (BALT). Additional important cells that function in the pulmonary lymphoid system include dendritic cells, Langherhans cells, macrophages, and plasma cells. An appreciation of the normal lymphoid anatomy of the lung as well as its immunology is helpful in understanding the radiologic and pathologic findings of the primary pulmonary lymphoid lesions. Primary lymphoid lesions of the lung arise from the BALT and are uncommon. However, they are increasingly recognized within the growing number of posttransplant patients as well as other patients who are receiving immunosuppressive therapies. Primary lymphoid lesions encompass a wide range of benign and malignant lesions. Benign lymphoid lesions of the lung include reactive lymphoid hyperplasia, follicular bronchiolitis, lymphoid interstitial pneumonia, and nodular lymphoid hyperplasia. Malignant lymphoid lesions of the lung include low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), other non-Hodgkin lymphomas, and Hodgkin lymphoma. Last, a miscellaneous group of primary lymphoid lesions includes lymphomatoid granulomatosis, posttransplant lymphoproliferative disorders, acquired immunodeficiency syndrome (AIDS)-related lymphoma, and intravascular lymphoma/lymphomatosis. These lesions are best evaluated with multidetector chest computed tomography. The radiologic findings of the primary lymphoid lesions are often nonspecific and are best interpreted in correlation with clinical data and pathologic findings. The purpose of this article is to review pulmonary lymphoid anatomy as well as the most common primary pulmonary lymphoid disorders. (©)RSNA, 2016. PMID:26761531

  16. Low grade gastric MALTOMA: Treatment strategies based on 10 year follow-up

    PubMed Central

    Lee, Sang Kil; Lee, Yong Chan; Chung, Jae Bock; Chon, Chae Yoon; Moon, Young Myoung; Kang, Jin Kyung; Park, In-Suh; Suh, Chang Ok; Yang, Woo Ik

    2004-01-01

    AIM: To deduce strategic guideline of gastric mucosa associated lymphoid tissue lymphoma (MALTOMA) by evaluating the long-term outcome of patients in respect to various treatment modalities. METHODS: A total of 55 patients with MALTOMA from May 1992 to August 2002 were retrospectively reviewed. RESULTS: Complete remission was obtained in 24 (82.8%) of 29 patients treated with anti Helicobacter pylori (H pylori) regimen only. The duration to reach complete remission was 12 months (85 percentile, 2-33 months). Five patients showed complete remission with radiation therapy (26-86 months). Two of them were H pylori treatment failure cases. CONCLUSION: H pylori eradication is an effective primary treatment option for low grade MALTOMA and radiation therapy could be considered in patients with no evidence of H pylori infection or who do not respond to H pylori eradication therapy 12 months after successful eradication. PMID:14716827

  17. Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2015-12-14

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma

  18. Lymphoid infiltrates of the salivary glands: pathology, biology and clinical significance.

    PubMed

    DiGiuseppe, J A; Corio, R L; Westra, W H

    1996-05-01

    Lymphoid infiltrates of the salivary glands are common to a variety of pathologic conditions including autoimmune disorders, malignant lymphomas, and immunoregulatory responses to parenchymal neoplasms. Clearly, the correct identification of these salivary gland lymphoid infiltrates has important implications regarding patient prognosis and management. Immunophenotypic and molecular analyses have demonstrated that many lesions formerly regarded as myoepithelial sialadentis or benign lymphoepithelial lesion in fact represent neoplastic lymphoid proliferations with the potential for extrasalivary dissemination. In the most recent classification scheme of non-Hodgkin's lymphomas, these neoplasms fall within the spectrum of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. In the early stages of HIV infection, patients may develop salivary gland enlargement resulting from cystic lymphoepithelial lesions. These lesions are thought to reflect a localized manifestation of persistent generalized lymphadenopathy. Although HIV-associated salivary gland disease is regarded as a benign condition, malignant lymphoma has been described in association with some of these lesions, and further work is required to define more precisely the risk of salivary gland lymphoma in HIV-infected patients. Tumor-associated lymphoid proliferation refers to a prominent lymphoid reaction accompanying certain epithelial tumors of the salivary glands. Although tumor-associated lymphoid proliferation has not received as much attention as other types of salivary lymphoid infiltrates, it is a common phenomenon that is sometimes mistaken for an intraparotid lymph node harboring metastatic carcinoma. PMID:8804813

  19. Mucosa-associated lymhpoid tissue (MALT) lymphoma of the jejunum and Helicobacter pylori--chance association?

    PubMed

    Keung, Yi-Kong; Higgs, Vetta; Albertson, David A; Cappellari, James O

    2003-08-01

    Helicobacter pylori have been causally linked to primary gastric B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Antibiotic therapy to eradicate H. pylori has been shown to induce remission of such lymphoma. We report a case of primary B-cell MALT lymphoma of the jejunum associated with H. pylori. The literature of intestinal MALT lymphoma is reviewed. PMID:12952237

  20. Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously arising in the colon and in the lung: report of a case.

    PubMed

    Sallach, S; Schmidt, T; Pehl, C; Gallenberger, S; Keiditsch, E; Starostik, P; Ott, G; Schepp, W

    2001-03-01

    zone B cell lymphoma of mucosa-associated lymphoid tissue type according to the Revised European American Lymphoma classification). Other mucosa-associated lymphoid tissue-type lymphomas arise in the salivary glands, thyroid gland, and in the lung (bronchus-associated lymphoid tissue). Here, we report the first case of a monoclonal mucosa-associated lymphoid tissue lymphoma with simultaneous manifestation in the colonic and bronchial mucosa in a 62-year-old patient. With mitoxantrone, chlorambucil, and prednisone polychemotherapy, a complete year-long remission was achieved. PMID:11289295

  1. Low-Grade Gliomas

    PubMed Central

    Forst, Deborah A.; Nahed, Brian V.; Loeffler, Jay S.

    2014-01-01

    Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated. PMID:24664484

  2. Low-grade glioma.

    PubMed

    Kumthekar, Priya; Raizer, Jeffrey; Singh, Simran

    2015-01-01

    Low-grade gliomas are slower growing than their high-grade counterparts. They account for 10-20 % of all primary brain tumors. Median survival is between 4.7 and 9.8 years. The goal of treatment is to prolong overall survival while maintaining good quality of life (QOL). Recent data favors early surgical resection. EOR is associated with delayed tumor recurrence and improved survival. Additional therapy with chemotherapy or radiation is indicated in patients with high-risk features. Lower doses (between 45 and 50.4 Gy) have been shown to be as effective without adverse effects compared to higher doses. Recent trials have shown benefit in combining chemotherapy with radiation compared to radiation alone. The optimal chemotherapeutic regimen (PCV or temozolomide (TMZ)) remains unknown, although TMZ is easier to administer and better tolerated by patients. Novel molecular markers including 1p/19q chromosomal codeletion and isocitrate dehydrogenase 1 (IDH1) mutation have been correlated with treatment response and survival. PMID:25468226

  3. Low Grade Gliomas in Children.

    PubMed

    Chalil, Alan; Ramaswamy, Vijay

    2016-03-01

    Gliomas represent the most common solid tumor of the nervous system, and can occur as both low and high-grade tumors. Current risk stratification and treatment approaches rely heavily on the morphological classification of gliomas whereby low-grade gliomas have an excellent prognosis, particularly pilocytic astrocytomas, while high-grade gliomas have a poor prognosis. The past decade has witnessed a dramatic increase in scholars' knowledge of the biology of pediatric low-grade gliomas particularly through the advent of integrated genomics and next generation sequencing. Indeed, many of these biological advances are changing treatment paradigms, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials. In this review the authors summarize the current approach to pediatric low grade gliomas and outline the biological advances over the past 10 years, which will be driving the next generation of clinical trials. PMID:26286938

  4. Elevation of serum interleukins 8, 4, and 1β levels in patients with gastrointestinal low-grade B-cell lymphoma

    PubMed Central

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-01-01

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P = 6.7E−05), IL-4 (P = 7.5E−05), and IL-1β (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 β levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development. PMID:26674732

  5. Elevation of serum interleukins 8, 4, and 1β levels in patients with gastrointestinal low-grade B-cell lymphoma.

    PubMed

    Miyata-Takata, Tomoko; Takata, Katsuyoshi; Toji, Tomohiro; Goto, Naoe; Kasahara, Senji; Takahashi, Takeshi; Tari, Akira; Noujima-Harada, Mai; Miyata, Takafumi; Sato, Yasuharu; Yoshino, Tadashi

    2015-01-01

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P = 6.7E-05), IL-4 (P = 7.5E-05), and IL-1β (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-1 β levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development. PMID:26674732

  6. Pediatric Low-Grade Gliomas

    PubMed Central

    Sievert, Angela J.; Fisher, Michael J.

    2010-01-01

    Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by supratentorial diffuse fibrillary astrocytomas. Recent research has implicated activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery is the mainstay of therapy. Overall survival rates for patients whose tumors are completely resected are 90% or greater, 10 years from diagnosis. Conversely, most optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal potential for resection; these tumors can be difficult to treat and deserve special attention. Combination chemotherapy is currently recommended as front-line adjuvant treatment for progressive or recurrent tumors. Second-line radiotherapy can also improve overall survival but is associated with more frequent and significant neurocognitive, endocrine, and other long-term toxicities. PMID:19841428

  7. Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

    ClinicalTrials.gov

    2015-01-16

    Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  8. TLR9 Agonist SD-101, Ipilimumab, and Radiation Therapy in Treating Patients With Low-Grade Recurrent B-cell Lymphoma

    ClinicalTrials.gov

    2015-05-19

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

  9. Characterization of the lymphoid stroma in Warthin's tumor of salivary gland by immunohistochemistry, heavy chain gene and Bcl-2 gene rearrangement.

    PubMed

    Song, Kunchang; Cotelingam, James D; Lowery-Nordberg, Mary; Sun, Wei

    2009-01-01

    Warthin's tumor is rarely associated with malignant lymphoma. Only 18 cases were reported in the literature so far. In most cases the latter is a low grade process, including Marginal zone/Mucosa associated lymphoid tissue (MALT) type lymphoma, follicular lymphoma, and rarely diffuse large cell lymphoma which may arise de novo or secondary to low grade lymphoma. This study was conducted to determine the prevalence of occult B cell monoclones and genetic alterations in Warthin's tumor. Fourteen cases of Warthin's tumor were stained with antibodies to CD3, CD20, kappa and lambda light chains. On six cases of randomly selected Warthin's tumor, polymerase chain reaction (PCR) of IgH gene rearrangement (IgH-GR) was performed on genomic DNA extracted from formalin-fixed paraffin embedded tissue. One case of primary salivary gland indolent B-cell lymphoma and 3 cases of sialadenitis were analyzed by the same methods for comparison. In all Warthin's tumor and sialadenitis cases most of lymphoid stroma was B cell phenotype and concentrated in germinal centers. T cells were mostly located between germinal centers. No light chain restriction was demonstrable by kappa and lambda immunostains. Molecular genetic studies failed to show IgH-GR by FISH and showed polyclonal by IgH PCR. In contrast, the lymphoma case showed a diffuse proliferation of small B cells with light chain restriction and a minor component of reactive T cells. FISH showed IgH-GR and bcl-2 gene translocation with monoclonality by IgH PCR. Our study concludes that the lymphoid stroma of Warthin's tumor is reactive. PMID:19956447

  10. Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

    ClinicalTrials.gov

    2016-02-03

    Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

  11. Quantification and characterization of mucosa-associated and intracellular Escherichia coli in inflamatory bowel disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background and aims: Mucosa-associated E. coli are abundant in Crohn’s disease (CD) but whether these bacteria gain intracellular access within the mucosa is less certain. If E. coli does gain intracellular access in CD, the contribution of bacterial pathogenicity as opposed to a defect in host inna...

  12. Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to H. pylori Infection Status

    PubMed Central

    Kim, Ju Seok; Kang, Sun Hyung; Moon, Hee Seok; Jeong, Hyun Yong

    2016-01-01

    Background. To evaluate the long-term outcome of H. pylori eradication therapy for gastric MALT lymphoma according to the presence of H. pylori infection. Methods. We retrospectively reviewed the medical records of patients between January 2001 and June 2014. The clinicopathologic characteristics and clinical outcomes were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphoma groups. Results. Fifty-four patients were enrolled: 12 H. pylori-negative and 42 H. pylori-positive patients. The tumor was located more frequently in both the proximal and distal parts of the stomach (P = 0.001), and the percentage of multiple lesions was significantly greater in the H. pylori-negative group (P = 0.046). Forty-seven patients received initial eradication therapy, and 85% (35/41) of H. pylori-positive patients and 50% (3/6) of H. pylori-negative patients achieved complete remission after eradication therapy. The presence of multiple lesions was a predictive factor for unresponsiveness to H. pylori eradication (P = 0.024). The efficacy of eradication therapy (P = 0.133), complete remission (CR) maintenance period, and relapse after eradication therapy were not significantly different between the two groups. Conclusions. H. pylori eradication therapy could be an effective first-line treatment for localized H. pylori-negative gastric MALT lymphoma, especially for single lesions.

  13. Nitinol engine for low grade heat

    SciTech Connect

    Li, Y.T.

    1981-12-01

    A continuous band of nitinol wrapping in between a cluster of tightly engaged rollers to form a series of s-shaped bends is used as the principle working medium of a thermal engine to convert low grade heat to mechanical power output. The band, together with the rollers, divides the space into an inner and an outer zone. A stream of warmer water and a stream of cooler water are guided to flow separately through one or the other of the two zones to make uniform and intimate contact with the segments of the nitinol band alternatively at appropriate intervals. A well defined four-cycle operation of temperature and stress is thus established and can convert a portion of the energy which is available in the thermal gradient of the two water streams into a mechanical shaft power which may be tapped from one of the rollers.

  14. Large retroperitoneal low-grade extraskeletal osteosarcoma

    PubMed Central

    Jaipuria, Jiten; Kumar, Ashok; Rao, Adla Satyanarayan; Kataria, Satya Pal

    2014-01-01

    Low-grade extraskeletal osteosarcoma is an extremely rare neoplasm with only nine cases reported in the literature, in which only one case involved the retroperitoneum. Tendency to dedifferentiate as well as recur with high-grade variant is known and management principles are not well defined, necessitating a continuous review of literature. We report management of the largest such retroperitoneal tumour (18.0 cm× 18.3 cm×17.8 cm) in a 38-year-old man, which was treated with surgery followed by six cycles of cisplatin (90 mg/m2 days 1 and 2) and doxorubicin (75 mg/m2 day 3), cycled every 3 weeks (with granulocyte colony stimulating factor support as necessary). The patient is disease free after 3 years of follow-up. PMID:24658529

  15. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

    PubMed

    Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

    2013-07-01

    Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma. PMID:23821212

  16. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota

    PubMed Central

    2014-01-01

    Background The microbiota of the mammalian gastrointestinal (GI) tract consists of diverse populations of commensal bacteria that interact with host physiological function. Dysregulating these populations, through exogenous means such as antibiotics or dietary changes, can have adverse consequences on the health of the host. Studies from laboratories such as ours have demonstrated that exposure to psychological stressors disrupts the population profile of intestinal microbiota. To date, such studies have primarily focused on prolonged stressors (repeated across several days) and have assessed fecal bacterial populations. It is not known whether shorter stressors can also impact the microbiota, and whether colonic mucosa-associated populations can also be affected. The mucosa-associated microbiota exist in close proximity to elements of the host immune system and the two are tightly interrelated. Therefore, alterations in these populations should be emphasized. Additionally, stressors can induce differential responses in anxiety-like behavior and corticosterone outputs in variant strains of mice. Thus, whether stressor exposure can have contrasting effects on the colonic microbiota in inbred C57BL/6 mice and outbred CD-1 mice was also examined. Results In the present study, we used high throughput pyrosequencing to assess the effects of a single 2-hour exposure to a social stressor, called social disruption (SDR), on colonic mucosa-associated microbial profiles of C57BL/6 mice. The data indicate that exposure to the stressor significantly changed the community profile and significantly reduced the relative proportions of two genera and one family of highly abundant intestinal bacteria, including the genus Lactobacillus. This finding was confirmed using a quantitative real-time polymerase chain reaction (qPCR) technique. The use of qPCR also identified mouse strain-specific differences in bacterial abundances. L. reuteri, an immunomodulatory species, was decreased in stressor-exposed CD-1 mice, but not C57BL/6 mice. Conclusions These data illustrate that stressor exposure can affect microbial populations, including the lactobacilli, that are closely associated with the colonic mucosa. Because the lactobacilli can have beneficial effects on human health, stressor-induced reductions of their population could have important health implications. PMID:25028050

  17. Low-grade and anaplastic oligodendroglioma.

    PubMed

    Van Den Bent, Martin J; Bromberg, Jacolien E C; Buckner, Jan

    2016-01-01

    Anaplastic oligodendrogliomas have long attracted interest because of their sensitivity to chemotherapy, in particular in the subset of 1p/19q co-deleted tumors. Recent molecular studies have shown that all 1p/19q co-deleted tumors have IDH mutations and most of them also have TERT mutations. Because of the presence of similar typical genetic alterations in astrocytoma and glioblastoma, the current trend is to diagnose these tumors on the basis of their molecular profile. Further long-term follow-up analysis of both EORTC and RTOG randomized studies on (neo)adjuvant procarbazine, lomustine, vincristine (PCV) chemotherapy have shown that adjuvant chemotherapy indeed improves outcome, and this is now standard of care. It is also equally clear that benefit to PCV chemotherapy is not limited to the 1p/19q co-deleted cases; potential other predictive factors are IDH mutations and MGMT promoter methylation. Moreover, a recent RTOG study on low-grade glioma also noted an improved outcome after adjuvant PCV chemotherapy, thus making (PCV) chemotherapy now standard of care for all 1p/19q co-deleted tumors regardless of grade. It remains unclear whether temozolomide provides the same survival benefit, as no data from well-designed clinical trials on adjuvant temozolomide in this tumor type are available. Another question that remains is whether one can safely leave out radiotherapy as part of initial treatment to avoid cognitive side-effects of radiotherapy. The current data suggest that delaying radiotherapy and treatment with chemotherapy only may be detrimental for overall survival. PMID:26948366

  18. Targeting of Nasal Mucosa-Associated Antigen-Presenting Cells In Vivo with an Outer Membrane Protein A Derived from Klebsiella pneumoniae

    PubMed Central

    Goetsch, Liliane; Gonzalez, Alexandra; Plotnicky-Gilquin, Hélène; Haeuw, Jean François; Aubry, Jean Pierre; Beck, Alain; Bonnefoy, Jean Yves; Corvaïa, Nathalie

    2001-01-01

    Administration of vaccines by the nasal route has recently proven to be one of the most efficient ways for inducing both mucosal and systemic antibody responses in experimental animals. Our results demonstrate that P40, a well-defined outer membrane protein A from Klebsiella pneumoniae, is indeed a carrier molecule suitable for nasal immunization. Using fragments from the respiratory syncytial virus subgroup A (RSV-A) G protein as antigen models, it has been shown that P40 is able to induce both systemic and mucosal immunity when fused or coupled to a protein or a peptide and administered intranasally (i.n.) to naive or K. pneumoniae-primed mice. Confocal analyses of nasal mucosa-associated lymphoid tissue after i.n. instillation of P40 showed that this molecule is able to cross the nasal epithelium and target CD11c-positive cells likely to be murine dendritic cells or macrophages. More importantly, this targeting of antigen-presenting cells following i.n. immunization with a subunit of the RSV-A molecule in the absence of any mucosal adjuvant results in both upper and lower respiratory tract protection against RSV-A infection. PMID:11553588

  19. Effects of feed additives on ileal mucosa-associated microbiota composition of broiler chickens.

    PubMed

    Ruiz, R; Peinado, M J; Aranda-Olmedo, I; Abecia, L; Surez-Pereira, E; Ortiz Mellet, C; Garca Fernndez, J M; Rubio, L A

    2015-07-01

    The effects of dietary supplementation with 2 recently developed feed additives on the composition of the mucosa-associated microbiota of the ileum were studied in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds each. The 2 additives tested were a di-d-fructose dianhydrideenriched caramel (FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary treatments were a control (commercial diet with no additive), INU (20 g inulin/kg diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this study, inulin supplementation resulted in lower (P < 0.05) and FC feeding resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of copies with respect to the controls was determined in the ileal mucosa of birds fed the PTS-Osupplemented diet. Denaturing gradient gel electrophoresis and PCR analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum, Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples from chickens fed the control and the PTS-Osupplemented diet. Bifidobacterium longum was exclusively found in poultry fed the control diet, whereas B. pseudocatenulatum was found only in poultry fed the PTS-Osupplemented diet. This study showed that both PTS-O and FC were able to modulate the composition of the ileal mucosa-associated microbiota of growing broiler chickens. Finally, in addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum, species not previously described in intestinal samples of broilers, was also demonstrated. PMID:26440010

  20. Bilateral femur metastases in low-grade endometrial carcinoma

    PubMed Central

    Lunardi, Pierre; Vidal, Fabien; Accadbled, Franck; Leguevaque, Pierre; Soule-Tholy, Marc; Beauval, Jean Baptiste; Motton, Stphanie

    2015-01-01

    Key Clinical Message Lower-limb bone metastases are uncommon in low-grade endometrial carcinoma, and are mostly located on the axial skeleton. Here, we present a rare case of bilateral femur metastases in low-grade endometrial carcinoma and performed a review of the current literature. PMID:26273447

  1. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel

    PubMed Central

    Langlands, S J; Hopkins, M J; Coleman, N; Cummings, J H

    2004-01-01

    Background and aims: The mucosa associated flora of the large intestine is important in determining mucosal function although what controls its composition is unknown. This study has determined the effect of the prebiotic carbohydrates oligofructose and inulin on the mucosal flora. Methods: An in vitro chemostat model of both planktonic and surface associated bacteria was used followed by an intervention study in 29 subjects undergoing colonoscopy. Subjects: Fourteen subjects, recruited from colonoscopy waiting lists, supplemented their diet for two weeks with a mix of 7.5 g of oligofructose and 7.5 g inulin. Fifteen subjects were recruited at the time of colonoscopy and given no supplement. Multiple endoscopic biopsies were taken from the caecum, transverse and descending colon, and rectum. The mucosal flora was characterised by culture and to species level by cellular fatty acid profiles. Cell proliferation was assessed by immunohistochemical staining for minichromosome maintenance protein 2, Ki67, and proliferating cell nuclear antigen. Results: In vitro prebiotics increased surface counts of bifidobacteria from 6.6 to 7.3 log10 colony forming units (CFU) per slide (p<0.0006) with no significant changes in planktonic bacteria. In the feeding study, prebiotics increased mucosal bifidobacteria (log CFU/g mucosa (SEM)) in both the proximal (control 5.3 (0.4) v prebiotic 6.3 (0.3)) (p = 0.059) and distal (control 5.2 (0.3) v prebiotic 6.4 (0.3)) colon (p = 0.01). Lactobacilli were also increased (3.0 (0.1) v 3.7 (0.2) (p = 0.02) in the proximal and 3.1 (0.1) v 3.6 (0.2) (p = 0.04) in the distal colon, respectively). There were significantly more eubacteria in fed subjects but no changes in total anaerobes clostridia, bacteroides, or coliforms, nor in proliferation indices. Conclusion: Prebiotic carbohydrates can change the composition of the mucosa associated flora significantly. PMID:15479681

  2. Desalination using low grade heat sources

    NASA Astrophysics Data System (ADS)

    Gude, Veera Gnaneswar

    A new, low temperature, energy-efficient and sustainable desalination system has been developed in this research. This system operates under near-vacuum conditions created by exploiting natural means of gravity and barometric pressure head. The system can be driven by low grade heat sources such as solar energy or waste heat streams. Both theoretical and experimental studies were conducted under this research to evaluate and demonstrate the feasibility of the proposed process. Theoretical studies included thermodynamic analysis and process modeling to evaluate the performance of the process using the following alternate energy sources for driving the process: solar thermal energy, solar photovoltaic/thermal energy, geothermal energy, and process waste heat emissions. Experimental studies included prototype scale demonstration of the process using grid power as well as solar photovoltaic/thermal sources. Finally, the feasibility of the process in reclaiming potable-quality water from the effluent of the city wastewater treatment plant was studied. The following results have been obtained from theoretical analysis and modeling: (1) The proposed process can produce up to 8 L/d of freshwater for 1 m2 area of solar collector and evaporation chamber respectively with a specific energy requirement of 3122 kJ for 1 kg of freshwater production. (2) Photovoltaic/thermal (PV/T) energy can produce up to 200 L/d of freshwater with a 25 m2 PV/T module which meets the electricity needs of 21 kWh/d of a typical household as well. This configuration requires a specific energy of 3122 kJ for 1 kg of freshwater production. (3) 100 kg/hr of geothermal water at 60C as heat source can produce up to 60 L/d of freshwater with a specific energy requirement of 3078 kJ for 1 kg of freshwater production. (4) Waste heat released from an air conditioning system rated at 3.25 kW cooling, can produce up to 125 L/d of freshwater. This configuration requires an additional energy of 208 kJ/kg of freshwater along with the waste heat released from the condenser of air-conditioning system. This additional energy requirement is about 60% of the energy required by a multi stage flash distillation process. The experimental studies were conducted in three phases. In the first phase, electric power from grid as energy source was used to demonstrate the feasibility of the proposed process. These tests showed that freshwater production rate of 0.25 kg/hr can be sustained at evaporation temperatures as low as 40C with specific energy input of 3,370 kJ/kg, at efficiencies ranging from 65 to 70% during the winter. In the second phase, experiments were conducted utilizing direct solar thermal energy and photovoltaic energy as well. Four different combinations of energy sources were studied. The following results were obtained from these experimental studies: (1) Utilizing direct solar energy produced 4.9 L/d of freshwater with an evaporator area of 1 m2 with an average efficiency of 61%. This yield is two times that can be obtained from a flat solar still. The specific energy requirement for this configuration is 4157 kJ for production of 1 kilogram freshwater; (2) Utilizing direct solar energy with aid of a reflector produced 7.5 L/d of freshwater with an average efficiency more than 80%. The specific energy requirement for this configuration is 3118 kJ for production of 1 kilogram freshwater; (3) Utilizing direct solar energy during sunlight hours and photovoltaic energy during non-sunlight hours produced 12 L/d of freshwater with 1 m2 evaporator area and 6 m2 photovoltaic areas respectively. The specific energy requirement for this configuration is 2926 kJ for production of 1 kilogram freshwater. Finally, the feasibility of this process in reclaiming potable-quality water from the effluent of a domestic wastewater treatment plant was studied. The process was able to achieve the following reductions: total dissolved solids from 727 mg/L to 21 mg/L (97%); nitrates from 2.4 mg/L to <0.1 mg/L (> 95%); ammonia from 23.2 mg/L to < 0.5 mg/L (> 97%); and

  3. Characteristics of Fecal and Mucosa-Associated Microbiota in Chinese Patients With Inflammatory Bowel Disease

    PubMed Central

    Chen, Liping; Wang, Wei; Zhou, Rui; Ng, Siew C.; Li, Jin; Huang, Meifang; Zhou, Feng; Wang, Xin; Shen, Bo; A. Kamm, Michael; Wu, Kaichun; Xia, Bing

    2014-01-01

    Abstract The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn’s disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD. PMID:25121355

  4. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer.

    PubMed

    Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Wu, Wen; Qin, Huanlong

    2015-10-01

    Studies using animal models have demonstrated that probiotics may have a beneficial role in the prevention of colorectal cancer (CRC); however, the underlying mechanism of the beneficial effects of interventional probiotic treatment on gut microbiota has remained elusive. In the present study, pyrosequencing of the V3 region of the 16S rRNA genes was conducted in order to determine the extent to which probiotics alter the microbiota. The observations of the present study indicated that the microbial structure of cancerous tissue differed significantly from that of healthy individuals and that the CRC microbiota exhibited lower diversity. It was indicated that interventional treatment with probiotics increased the density and diversity of mucosal microbes, and altered the mucosa‑associated microbiota. Pyrosequencing demonstrated that probiotics significantly reduced (5‑fold) the abundance of a bacterial taxon assigned to the genus Fusobacterium, which had been previously suggested to be a contributing factor to increase tumorigenesis. Accordingly, interventional probiotic therapy is suggested to be able to improve the composition of the mucosal microbial flora and significantly reduce the abundance of mucosa-associated pathogens in patients with CRC. PMID:26238090

  5. Mucosa-associated Faecalibacterium prausnitzii phylotype richness is reduced in patients with inflammatory bowel disease.

    PubMed

    Lopez-Siles, Mireia; Martinez-Medina, Margarita; Abell, Carles; Busquets, David; Sabat-Mir, Miriam; Duncan, Sylvia H; Aldeguer, Xavier; Flint, Harry J; Garcia-Gil, L Jess

    2015-11-01

    Faecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis. PMID:26296733

  6. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer.

    PubMed

    Chen, Weiguang; Liu, Fanlong; Ling, Zongxin; Tong, Xiaojuan; Xiang, Charlie

    2012-01-01

    Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; however the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host. PMID:22761885

  7. Mucosa-Associated Bacterial Microbiome of the Gastrointestinal Tract of Weaned Pigs and Dynamics Linked to Dietary Calcium-Phosphorus

    PubMed Central

    Mann, Evelyne; Schmitz-Esser, Stephan; Zebeli, Qendrim; Wagner, Martin; Ritzmann, Mathias; Metzler-Zebeli, Barbara U.

    2014-01-01

    Dietary composition largely influences pigs gastrointestinal microbiota and represents a useful prophylactic tool against enteric disturbances in young pigs. Despite the importance for host-microbe interactions and bacterial colonization, dietary responses of the mucosa-associated bacterial communities are less well investigated. In the present study, we characterized the mucosa-associated bacterial communities at the Pars non-glandularis of the stomach, ileum and colon, and identified shifts in these communities in response to different dietary calcium-phosphorus (Ca-P) contents (100% versus 190% of the Ca and P requirements) in combination with two basal diets (wheat-barley- or corn-based) in weaned pigs. Pyrosequencing of 16S rRNA genes from 93 mucosal samples yielded 447,849 sequences, clustering into 997 operational taxonomic units (OTUs) at 97% similarity level. OTUs were assigned to 198 genera belonging to 14 different phyla. Correlation-based networks revealed strong interactions among OTUs at the various gastrointestinal sites. Our data describe a previously not reported high diversity and species richness at the Pars non-glandularis of the stomach in weaned pigs. Moreover, high versus adequate Ca-P content significantly promoted Lactobacillus by 14.9% units (1.4 fold change) at the gastric Pars non-glandularis (P?=?0.035). Discriminant analysis revealed dynamic changes in OTU composition in response to dietary cereals and Ca-P contents at all gastrointestinal sites which were less distinguishable at higher taxonomic levels. Overall, this study revealed a distinct mucosa-associated bacterial community at the different gut sites, and a strong effect of high Ca-P diets on the gastric community, thereby markedly expanding our comprehension on mucosa-associated microbiota and their diet-related dynamics in weaned pigs. PMID:24466298

  8. Characterization of the gastrointestinal mucosa-associated microbiota of pigs and chickens using culture-based and molecular methodologies.

    PubMed

    Collado, M Carmen; Sanz, Yolanda

    2007-12-01

    The microbiota of the gastrointestinal tract (GIT) can play an important role in the healthy status of farm animals and in the safety of the whole food chain. In this study, the mucosa-associated microbiota of the GIT of pigs and chickens was analyzed by culture methods and fluorescence in situ hybridization combined with flow cytometry (FCM-FISH). In all pig GIT sections, lactic acid bacteria, Enterobacteriaceae, Atopobium, Bacteroides, and Clostridium histolyticum were the predominant bacterial groups. Atopobium, Bifidobacterium, Bacteroides, and Lactobacillus were detected at higher levels (P < 0.05) in the intestine than in the stomach. In all broilers' GIT sections, lactic acid bacteria, Atopobium, Bacteroides, and Escherichia coli were the predominant bacterial groups. Atopobium, Bifidobacterium, E. coli, and Eubacterium rectale--Clostridium coccoides counts were significantly higher (P < 0.05) in the crop, while those of Bacteroides and Lactobacillus were higher (P < 0.05) in the large intestine. Lactic acid bacteria were one of the predominant GIT mucosa-associated bacteria of pigs and broilers, which could be an index of their healthy status. FCM-FISH analysis also allowed the detection of bacterial groups hard to cultivate yet quantitatively important. The distribution of Lactobacillus and Bacteroides followed the same trend in both animal species, whereas that of Atopobium and Bifidobacterium was the opposite. These results contribute to the knowledge on the diversity and distribution of the animal GIT mucosa-associated microbiota. PMID:18095433

  9. Low-Grade Oligodendroglioma of the Pineal Region: Case Report

    PubMed Central

    Lamis, Fabricio Correa; de Paiva Neto, Manoel Antonio; Stavale, Joo Norberto; Cavalheiro, Sergio

    2015-01-01

    Background?Although germ cell tumors and pineal cell tumors account for most of the histologic tumor subtypes,?>?17 different tumors can arise in this location. We report a rare case of a low-grade oligodendroglioma that arose in the pineal region. Clinical Presentation?A young woman complaining of a headache underwent magnetic resonance imaging that showed a mass in the pineal region and mild hydrocephalus. A ventriculoperitoneal shunt was performed followed by a near-total tumor removal, due to tumor invasion of the tectal plate and thalamus. The histologic examination confirmed the diagnosis of a low-grade oligodendroglioma. The patient then underwent chemotherapy and radiotherapy as adjuvant therapies. Conclusion?Although the pineal region is a common place for a large number of tumoral lesions, low-grade oligodendrogliomas are extremely rare in this location. This case is only the second account of a benign oligodendroglioma of the pineal region reported in the literature. PMID:26251811

  10. Pathological and Molecular Advances in Pediatric Low Grade Astrocytoma

    PubMed Central

    Rodriguez, Fausto J.; Lim, Kah Suan; Bowers, Daniel; Eberhart, Charles G.

    2013-01-01

    Pediatric low grade astrocytomas are the commonest brain tumors in children. They sometimes have similar microscopic and clinical features, making accurate diagnosis difficult. For patients whose tumors are in locations that do not permit full resection, or those with an intrinsically aggressive biology, more effective therapies are required. Until recently, little was known about the molecular changes that drive the initiation and growth of pilocytic and other low grade astrocytomas beyond the association of a minority of cases, primarily in the optic nerve, with neurofibromatosis type 1. Over the last several years, a wide range of studies have implicated the BRAF oncogene and other members of this signaling cascade in the pathobiology of pediatric low grade astrocytoma. In this review, we attempt to summarize this rapidly developing field, and discuss the potential for translating our growing molecular knowledge into improved diagnostic and prognostic biomarkers and new targeted therapies. PMID:23121055

  11. Low-Grade Carotid Stenosis: Implications of MR Imaging.

    PubMed

    Mossa-Basha, Mahmud; Wasserman, Bruce A

    2016-02-01

    Although treatment guidelines are well established for symptomatic patients with greater than 69% carotid stenosis on catheter angiography, optimal management of lower degrees of stenosis remain unclear. Vessel wall MR imaging of the carotid arteries has proved helpful in the evaluation of plaque burden and vulnerable plaque characteristics, and in stratifying risk in low-grade carotid stenosis. This article discusses the pathophysiology and imaging of atherosclerotic plaques resulting in low-grade carotid stenosis, and the corresponding stroke risk and association with plaque elsewhere in the cardiovascular system. PMID:26610665

  12. Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

    SciTech Connect

    Goda, Jayant Sastri; Le, Lisa W.; Lapperriere, Normand J.; Millar, Barbara-Ann; Payne, David; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Simpson, Rand; Tsang, Richard W.

    2011-11-15

    Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

  13. Low-grade inflammatory polarization of monocytes impairs wound healing.

    PubMed

    Yuan, Ruoxi; Geng, Shuo; Chen, Keqiang; Diao, Na; Chu, Hong Wei; Li, Liwu

    2016-03-01

    Impaired wound healing often accompanies low-grade inflammatory conditions, during which circulating levels of subclinical super-low-dose endotoxin may persist. Low-grade inflammatory monocyte polarization may occur during chronic inflammation and deter effective wound repair. However, little is understood about the potential mechanisms of monocyte polarization by sustained insult of subclinical super-low-dose endotoxin. We observed that super-low-dose endotoxin preferentially programmes a low-grade inflammatory monocyte state in vitro and in vivo, as represented by the elevated population of CD11b(+) Ly6C(high) monocytes and sustained expression of CCR5. Mechanistically, super-low-dose endotoxin caused cellular stress, altered lysosome function and increased the transcription factor IRF5. TUDCA, a potent inhibitor of cellular stress, effectively blocked monocyte polarization and improved wound healing in mice injected with super-low-dose endotoxin. Our data revealed the polarization of low-grade inflammatory monocytes by sustained endotoxin challenge, its underlying mechanisms and a potential intervention strategy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690561

  14. Low-Grade Epithelial Proliferations of the Sinonasal Tract.

    PubMed

    Bullock, Martin J

    2016-03-01

    Low-grade epithelial proliferations of the sinonasal tract include Schneiderian papillomas, respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma and low-grade non-intestinal adenocarcinoma. There is considerable overlap in their clinical presentation, endoscopic appearance, and imaging features. Although well-described diagnostic criteria exist, a definitive diagnosis may be difficult to reach on a small biopsy. Schneiderian papillomas are divided into fungiform, inverted, and oncocytic types, each with characteristic clinical and morphological features. The latter two may progress to malignancy. The majority are still considered to be HPV-related. Two lesions are designated as hamartomas, but their pathogenesis remains uncertain, with inflammatory and neoplastic origins proposed. Respiratory epithelial adenomatoid hamartoma is increasingly being recognized for its association with chronic rhinosinusitis and olfactory cleft site of origin. Seromucinous hamartoma has gained attention in recent years and overlaps with both respiratory epithelial adenomatoid hamartoma and low-grade non-intestinal adenocarcinoma. Controversy surrounds their distinction, particularly from low-grade adenocarcinoma. The latter generally is cured by complete excision, with a 26% risk of recurrence but rare metastases and deaths from disease. PMID:26830403

  15. Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

    ERIC Educational Resources Information Center

    Ris, M. Douglas; Beebe, Dean W.

    2008-01-01

    As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by

  16. Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?

    PubMed

    Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao

    2016-01-01

    "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs. PMID:26166721

  17. Validation of Use of Rectoanal Mucosa-Associated Lymphoid Tissue for Immunohistochemical Diagnosis of Chronic Wasting Disease in White-Tailed Deer (Odocoileus virginianus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transmissible spongiform encephalopathies are a family of fatal neurodegenerative diseases characterized by accumulation of abnormal prion proteins in the brain. The abnormal prion protein is the major constituent of the infectious agent and is a reliable marker for disease. The occurrence of ...

  18. Primary urinary bladder mucosa associated lymphoid tissue type lymphoma presenting as a close mimic for genitourinary tuberculosis: Case report and review of literature

    PubMed Central

    Jitani, Ankit Kumar; Mishra, Jaya; Sailo, Stephen L.; Raphael, Vandana

    2016-01-01

    Primary lymphoma of the urinary bladder is a rare entity. It has a distinctively different presentation than the urothelial carcinoma, which is the most common form of bladder cancer, but might mimic inflammatory lesions such as tubercular cystitis, clinically as well as radiologically. We present a case of primary extranodal marginal zone lymphoma of the bladder, which was a close mimicker of tuberculosis, leading to delay in diagnosis. We highlight the role of biopsy in prompt diagnosis of these cases. We emphasize on the high index of suspicion required to identify such cases at an early stage, which has pronounced prognostic implications. PMID:26834416

  19. Tubal origin of 'ovarian' low-grade serous carcinoma.

    PubMed

    Li, Jie; Abushahin, Nisreen; Pang, Shujie; Xiang, Li; Chambers, Setsuko K; Fadare, Oluwole; Kong, Beihua; Zheng, Wenxin

    2011-11-01

    Ovarian low-grade serous carcinomas are thought to evolve in a stepwise fashion from ovarian epithelial inclusions, cystadenomas, and borderline tumors. The current study was designed to gain insight into the origins of low-grade serous carcinomas (tubal versus ovarian) by comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic (using antibodies to PAX8, tubulin, calretinin, and Ki67) attributes of its putative precursor lesions, the normal tubal epithelium, and the overt malignancy. A total of 226 adnexal tissues from 178 patients were studied, including 98 adnexae removed for non-neoplastic indications, 48 serous cystadenomas, 42 serous borderline tumors, and 38 low-grade serous carcinomas. Normal distal tubal epithelium comprised an admixture of PAX8+/tubulin- secretory cells and PAX8-/tubulin+ ciliated cells with a proliferative index of ?3%. The vast majority of ovarian surface epithelia displayed a mesothelial phenotype (calretinin+/PAX8-/tubulin-) and low proliferative index (0% (12 per 1000)), although 4% of cases also displayed foci with tubal phenotype (calretinin-/PAX8+/tubulin+). In contrast, most (78%) of the ovarian epithelial inclusions displayed a tubal phenotype and had a significantly higher proliferative index (1%) than ovarian surface epithelium, indicating that in most cases, the ovarian surface epithelium and ovarian epithelial inclusions are of different lineages. There was a progressive decrease in the population of ciliated cells, as evidenced by increasing secretory/ciliated cell ratio, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, indicating that the latter is a clonal expansion of secretory cells. Overall, the findings make a strong argument that the ovarian epithelial inclusions with a tubal phenotype is likely derived from fallopian tube through an intraovarian endosalpingiosis rather than through Mullerian metaplasia from ovarian surface epithelium. Genetic and molecular studies are needed to further confirm this finding as tubal origination of ovarian serous cancers will have a significant impact on ovarian cancer prevention and management. PMID:21701538

  20. Notch Signaling Activation in Pediatric Low-Grade Astrocytoma

    PubMed Central

    Brandt, William D.; Schreck, Karisa C.; Bar, Eli E.; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G.; Rodriguez, Fausto J.

    2014-01-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in development, stem cell biology, and the pathogenesis of several cancers but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomical sites compared to non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res 186 and Res 259 using either RNA interference or a ?-secretase inhibitor resulted in variable but significant reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. PMID:25575134

  1. Notch signaling activation in pediatric low-grade astrocytoma.

    PubMed

    Brandt, William D; Schreck, Karisa C; Bar, Eli E; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G; Rodriguez, Fausto J

    2015-02-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a ?-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. PMID:25575134

  2. Platelet activation in atherogenesis associated with low-grade inflammation.

    PubMed

    Antoniades, Charalambos; Bakogiannis, Constantinos; Tousoulis, Dimitris; Demosthenous, Michael; Marinou, Kyriakoula; Stefanadis, Christodoulos

    2010-12-01

    Further to the established role of platelets in thrombosis and hemostasis, increasing evidence suggests that they also play a crucial role in atherogenesis. Platelets produce a number of agents contributing to the systemic low-grade inflammation implicated in atherogenesis. Platelet activation following inflammatory stimulus leads to the expression of surface receptors such as GPIb/IX/V, P-selectin, CD40, and to the release of several pro-inflammatory agents. Platelet receptors and released molecules play a critical role during the initiation and the progression of atherosclerosis by mediating leukocytes recruitment and adhesion to the vascular wall. Endothelial dysfunction, an early feature in atherosclerosis, is associated with low-grade inflammation within the vascular wall, and it leads to the reduced bioavailability of nitric oxide. Dysfunctional endothelium itself releases inflammatory molecules leading toward platelets activation and adhesion to the vascular wall. Platelets are no longer considered simply as cells participating in thrombosis. They are regulators of multiple processes in the human body, including inflammation, regulation of endothelial physiology and atherogenesis. The design of new therapeutic strategies targeting platelets and their impact in atherosclerosis-related low-grade inflammation are in the center of current cardiovascular research. PMID:20632958

  3. Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation.

    PubMed

    Wang, Lirui; Fouts, Derrick E; Strkel, Peter; Hartmann, Phillipp; Chen, Peng; Llorente, Cristina; DePew, Jessica; Moncera, Kelvin; Ho, Samuel B; Brenner, David A; Hooper, Lora V; Schnabl, Bernd

    2016-02-10

    Approximately half of all deaths from liver cirrhosis, the tenth leading cause of mortality in the United States, are related to alcohol use. Chronic alcohol consumption is accompanied by intestinal dysbiosis and bacterial overgrowth, yet little is known about the factors that alter the microbial composition or their contribution to liver disease. We previously associated chronic alcohol consumption with lower intestinal levels of the antimicrobial-regenerating islet-derived (REG)-3 lectins. Here, we demonstrate that intestinal deficiency in REG3B or REG3G increases numbers of mucosa-associated bacteria and enhances bacterial translocation to the mesenteric lymph nodes and liver, promoting the progression of ethanol-induced fatty liver disease toward steatohepatitis. Overexpression of Reg3g in intestinal epithelial cells restricts bacterial colonization of mucosal surfaces, reduces bacterial translocation, and protects mice from alcohol-induced steatohepatitis. Thus, alcohol appears to impair control of the mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease. PMID:26867181

  4. Total lymphoid irradiation

    SciTech Connect

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  5. Decompression without Fusion for Low-Grade Degenerative Spondylolisthesis

    PubMed Central

    Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Cheung, Kenneth Man Chee

    2016-01-01

    Study Design Retrospective series. Purpose Assess results of decompression-only surgery for low-grade degenerative spondylolisthesis with consideration of instability. Overview of Literature There is no consensus on whether fusion or decompression-only surgery leads to better outcomes for patients with low-grade degenerative spondylolisthesis. Current trends support fusion but many studies are flawed due to over-generalization without consideration of radiological instability and their variable presentations and natural history. Methods Patients with surgically treated degenerative spondylolisthesis from 1990–2013 were included. Clinical and radiological instability measures were included. Any residual or recurrence of symptoms, revision surgery performed and functional outcome scores including the numerical global rate of change scale, visual analogue scale, and modified Barthel index were measured. Follow-up periods for patients were divided into short-term (<5 years), mid-term (5–10 years) and long-term (>10 years). Results A total of 64 patients were recruited. Mechanical low back pain was noted in 48 patients and most (85.4%) had relief of back pain postoperatively. Radiological instability was noted in 4 subjects by flexion-extension radiographs and 12 subjects with prone traction radiographs by increased disc height and reduction of olisthesis and slip angle. From the results of the short-term, mid-term and long-term follow-up, reoperation only occurred within the first 5-year follow-up period. All functional scores improved from preoperative to postoperative 1-year follow-up. Conclusions Decompression-only for low-grade degenerative spondylolisthesis has good long-term results despite instability. Further higher-level studies should be performed on this patient group with radiological instability to suggest the superior surgical option. PMID:26949462

  6. Low Grade Fibromyxoid Sarcoma of the Palate: A Case Report

    PubMed Central

    Bhat, Shriram; Shetty, Sunil Kumar

    2015-01-01

    Low-grade fibromyxoid sarcoma (LGFMS) are rare soft-tissue sarcomas that usually come to attention as slow growing masses. Males and females are affected approximately equally and typically arising in the soft tissue of the proximal extremities. Primary occurrence within the head and neck is exceedingly rare. We report a case arising from the hard palate of a 40-year-old male and according to our knowledge this is the first ever case of LGFMS involving the palate to be reported. PMID:26557602

  7. Brittle frictional mountain building 3. Low-grade metamorphism

    NASA Astrophysics Data System (ADS)

    Barr, Terence D.; Dahlen, F. A.; McPhail, D. C.

    1991-06-01

    An active fold-and-thrust belt in unchanging tectonic and climatic conditions exhibits a dynamic steady state, with the flux of rocks accreted at the toe balanced by the flux of rocks eroded off the top. Rocks entering the toe are buried and heated before they are uplifted and eroded; this results in a characteristic map pattern of low-grade metamorphism on the surface. Metamorphic isograds are generally parallel to the regional strike of a fold-and-thrust belt, with the grade increasing progressively from unmetamorphosed and zeolite facies near the deformation front up to greenschist facies in the highest mountains; such a pattern is observed in the active fold-and-thrust belt of Taiwan. This paper examines the origin of this low-grade syntectonic metamorphism, using a previously developed mechanical and thermal model of a steady state fold-and-thrust belt as a basis. To model the metamorphism, we develop a petrogenetic grid for rocks of basaltic composition, considering phases within the chemical system CaO-MgO-Al2O3-SiO2-H2O. Equilibria diagnostic of stable low-grade mineral assemblages are mapped onto a cross section of the Taiwan fold-and-thrust belt, using the calculated fluid pressure and temperature distributions within the wedge. The variation of metamorphic grade along the surface is predicted by assuming that there is no retrograde metamorphism. The most important mechanical factor controlling the degree of metamorphism in an active fold-and-thrust belt is the amount of frictional heating, both on the basal decollement fault and within the deforming brittle wedge. Frictional heating raises temperatures in the deepest portions of the Taiwan fold-and-thrust belt by 200 C to 250 C; the resulting high temperatures, in excess of 400 C, are responsible for the extensive greenschist facies metamorphism. The amount of heating is well constrained by the observed heat flow anomaly, geochronological data, and the critical wedge taper; the best-fitting coefficient of basal friction in Taiwan is ?b = 0.5 0.2. Underplating of footwall rocks by the assimilation of duplexes along the decollement fault is not considered to be a significant process in Taiwan, because of the observed balance between the accretionary influx at the toe and the erosive efflux off the top. In other fold-and-thrust belts, however, underplating can significantly increase the outcrop width of higher metamorphic grades on the surface by increasing the flux of rocks through the higher fluid pressure and temperature regions within the wedge.

  8. Lymphoid microenvironments and innate lymphoid cells in the gut.

    PubMed

    Pearson, Claire; Uhlig, Holm H; Powrie, Fiona

    2012-06-01

    Gut-associated lymphoid tissue (GALT) is a sensor region for luminal content and plays an important role in lymphoid maturation, activation and differentiation. It comprises isolated and aggregated lymphoid follicles, cryptopatches (CPs) and tertiary lymphoid tissue. Innate lymphoid cells (ILCs) play a central role within GALT. Prenatal GALT development is dependent on ILC lymphoid-inducer function. Postnatally, these cells rapidly respond to commensal and pathogenic intestinal bacteria, parasites and food components by polarized cytokine production [such as interleukin (IL)-22, IL-17 or IL-13] and further contribute to GALT formation and function. Here, we discuss how ILCs shape lymphoid intestinal microenvironments and act as amplifier cells for innate and adaptive immune responses. PMID:22578693

  9. Extrachromosomal driver mutations in glioblastoma and low grade glioma

    PubMed Central

    Garieri, Marco; Makrythanasis, Periklis; Falconnet, Emilie; Guipponi, Michel; Vannier, Anne; Radovanovic, Ivan; Bena, Frederique; Forestier, Françoise; Schaller, Karl; Dutoit, Valerie; Clement-Schatlo, Virginie; Dietrich, Pierre-Yves; Antonarakis, Stylianos E

    2014-01-01

    Alteration of the number of copies of Double Minutes (DMs) with oncogenic EGFR mutations in response to tyrosine kinase inhibitors (TKIs) is a novel adaptive mechanism of glioblastoma. Here we provide evidence that such mutations in DMs, called here Amplification-Linked Extrachromosomal Mutations (ALEMs), originate extrachromosomally and could therefore be completely eliminated from the cancer cells. By exome sequencing of 7 glioblastoma patients we reveal ALEMs in EGFR, PDGFRA and other genes. These mutations together with DMs are lost by cancer cells in culture. We confirm the extrachromosomal origin of such mutations by showing that wild type and mutated DMs may coexist in the same tumor. Analysis of 4198 tumors suggests the presence of ALEMs across different tumor types with the highest prevalence in glioblastomas and low grade gliomas. The extrachromosomal nature of ALEMs explains the observed drastic changes in the amounts of mutated oncogenes (like EGFR or PDGFRA) in glioblastoma in response to environmental changes. PMID:25471132

  10. Low-grade heat recuperation by the organic Rankine cycle

    NASA Astrophysics Data System (ADS)

    Verneau, A.

    1980-11-01

    The use of an organic Rankine cycle engine in the conversion of low-grade industrial waste heat into mechanical energy is examined. The principles of a Rankine system using a vapor as the working fluid at operating temperatures from 100 to 500 C are presented, and the advantages of using organic vapors rather than water in the Rankine cycle are pointed out. Attention is then given to the Rankine cycle itself, the organic fluids employed, the multistage low-power turbines and the evaporator, which acts as a countercurrent heat exchanger. Economic aspects of the use of Rankine cycle systems for industrial waste heat recovery are then considered, and examples are presented of the calculation of power recovered and investment costs for the examples of heat recovery from diesel exhaust and from low-pressure steam.

  11. Interaction of low-grade metamorphic coals with methanol

    SciTech Connect

    S.I. Zherebtsov

    2007-06-15

    How conditions of alkylation of low-grade metamorphic coals with methanol in the presence of benzenesulfonic acid influence the yield of extractable matter was experimentally studied and relevant regression equations were obtained. It was shown that catalytic methylation considerably increases the yield of the extractable matter, as well as reducing the thermal stability of modified samples and alters the elemental composition of the samples and their extracts. A possible mechanism of coal methylation is discussed on the basis of regression models and experimental results. The interaction of the coal matter with the alkylating agent presumably involves the formation of the carbocation and its reaction with the coal organic matter. Both depolymerization reactions and the addition reactions of a portion of extractable compounds, the alkylating agent, and the catalyst with the high-molecular mass coal matrix take place.

  12. Reductive Leaching of Low-Grade Pyrolusite with Formic Acid

    NASA Astrophysics Data System (ADS)

    Lu, Youzhi; Ma, Huaju; Huang, Runjun; Yuan, Aiqun; Huang, Zengwei; Zhou, Zeguang

    2015-08-01

    The extraction of manganese from low-grade pyrolusite is investigated using formic acid as reductant in sulfuric acid medium. The effects of volumes of formic acid, concentration of sulfuric acid, liquid to solid ratio (L/S), leaching time, and temperature on leaching efficiency of manganese, iron, and aluminum are valuated with single-factor experiments. The results show that the leaching efficiency of manganese reached 90.08 pct with 80.70 pct of iron and 31.55 pct of aluminum under the optical conditions: 15 pct H2SO4(v/v) 60 ml, 4 ml formic acid, and 2 hours leaching time at 363 K (90 C).

  13. Low Grade Myofibroblastic Sarcoma Occurred in the Scalp

    PubMed Central

    Yee, Gi Taek

    2015-01-01

    Low-grade myofibroblastic sarcoma (LGMS) is a rare sarcoma with myofibroblastic differentiation. LGMS has a propensity for local recurrence and is associated with a low risk of metastatic spread. A 26-year-old man presented with a 12-month history of a slow growing palpable hard mass in the right parietal scalp. Enhanced CT scan of head showed a 34 cm sized well-defined and heterogeneously enhancing scalp mass. The patient underwent excision of the tumor. The histological and immunohistochemical features were consistent with a LGMS. We performed re-operation for remnant tumor removal after diagnosis. After 14 months of surgery, the patient was well-being state. PMID:26587195

  14. Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

    PubMed Central

    Kerckhoffs, Angle PM; Samsom, Melvin; van der Rest, Michel E; de Vogel, Joris; Knol, Jan; Ben-Amor, Kaouther; Akkermans, Louis MA

    2009-01-01

    AIM: To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome (IBS) patients and healthy subjects using molecular-based techniques. METHODS: Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization (FISH) and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction. RESULTS: The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria (4.2 1.3 vs 8.3 1.9, P < 0.01) in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower (6 0.6 vs 19 2.5, P < 0.001) in the IBS patients in both fecal and duodenal brush samples than in healthy subjects. CONCLUSION: Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology. PMID:19533811

  15. Regional differences in colonic mucosa-associated microbiota determine the physiological expression of host heat shock proteins

    PubMed Central

    Hu, Shien; Wang, Yunwei; Lichtenstein, Lev; Tao, Yun; Musch, Mark W.; Jabri, Bana; Antonopoulos, Dionysios; Claud, Erika C.

    2010-01-01

    Cytoprotective heat shock proteins (Hsps) are critical for intestinal homeostasis and are known to be decreased in inflammatory bowel diseases. Signals responsible for maintenance of Hsp expression are incompletely understood. In this study, we find that Hsp25/27 and Hsp70 protein expressions are differentially regulated along the longitudinal length of the large intestine, being highest in the proximal colon and decreasing to the distal colon. This longitudinal gradient was similar in both conventionally colonized mouse colon as well as biopsies of human proximal and distal colon but was abolished in the colon of germ-free mice, suggesting a role of intestinal microbiota in the Hsp regional expression. Correspondingly, analysis of 16S ribosomal RNA genes of bacteria from each colonic segment indicated increased bacterial richness and diversity in the proximal colon. The mechanism of regulation is transcriptional, as Hsp70 mRNA followed a similar pattern to Hsp70 protein expression. Lysates of mucosa-associated bacteria from the proximal colon stimulated greater Hsp25 and Hsp70 mRNA transcription and subsequent protein expression in intestinal epithelial cells than did lysates from distal colon. In addition, transrectal administration of cecal contents stimulated Hsp25 and Hsp70 expression in the distal colon. Thus host-microbial interactions resulting in differential Hsp expression may have significant implications for the maintenance of intestinal homeostasis and possibly for development of inflammatory diseases of the bowel. PMID:20864653

  16. Grain-rich diets altered the colonic fermentation and mucosa-associated bacterial communities and induced mucosal injuries in goats.

    PubMed

    Ye, Huimin; Liu, Junhua; Feng, Panfei; Zhu, Weiyun; Mao, Shengyong

    2016-01-01

    Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n?=?6) or an HG diet (65% grain; n?=?6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-? in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon. PMID:26841945

  17. Grain-rich diets altered the colonic fermentation and mucosa-associated bacterial communities and induced mucosal injuries in goats

    PubMed Central

    Ye, Huimin; Liu, Junhua; Feng, Panfei; Zhu, Weiyun; Mao, Shengyong

    2016-01-01

    Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n = 6) or an HG diet (65% grain; n = 6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-γ in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon. PMID:26841945

  18. Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas

    SciTech Connect

    Oh, Kevin S.; Hung, Jonathan; Robertson, Patricia L.; Garton, Hugh J.; Muraszko, Karin M.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

  19. Low-grade albuminuria in children with obstructive sleep apnea.

    PubMed

    Varlami, Vasiliki; Malakasioti, Georgia; Alexopoulos, Emmanouel I; Theologi, Vasiliki; Theophanous, Eleni; Liakos, Nikolaos; Daskalopoulou, Euphemia; Gourgoulianis, Konstantinos; Kaditis, Athanasios G

    2013-06-01

    Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1) ; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1) ; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes∙h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea. PMID:23228180

  20. Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms

    PubMed Central

    Nishikawa, G; Sekine, S; Ogawa, R; Matsubara, A; Mori, T; Taniguchi, H; Kushima, R; Hiraoka, N; Tsuta, K; Tsuda, H; Kanai, Y

    2013-01-01

    Background: The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown. Methods: Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line. Results: A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (09%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo. Conclusion: Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN. PMID:23403822

  1. Second Surgery in Insular Low-Grade Gliomas

    PubMed Central

    Ius, Tamara; Pauletto, Giada; Cesselli, Daniela; Isola, Miriam; Turella, Luca; Budai, Riccardo; DeMaglio, Giovanna; Eleopra, Roberto; Fadiga, Luciano; Lettieri, Christian; Pizzolitto, Stefano; Beltrami, Carlo Alberto; Skrap, Miran

    2015-01-01

    Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR) are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs) that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs). Univariate analysis showed that TR is influenced by the following: extent of resection (EOR) (P < 0.002), ?VT2T1 value (P < 0.001), histological diagnosis of oligodendroglioma (P = 0.017), and mutation of IDH1 (P = 0.022). The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P < 0.001). Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery. PMID:26539503

  2. Ruptured appendiceal diverticula mimicking low-grade appendiceal mucinous neoplasms.

    PubMed

    Hsu, Maylee; Young, Robert H; Misdraji, Joseph

    2009-10-01

    Low-grade appendiceal mucinous neoplasms may rupture and seed the peritoneum with bland neoplastic mucinous epithelium resulting, when grossly evident, in the well-known process pseudomyxoma peritonei. Appendiceal diverticula may also rupture, resulting in mucin on the appendiceal serosa, which may raise concern for an underlying appendiceal mucinous neoplasm. We report 11 cases of ruptured appendiceal diverticula that were initially either misdiagnosed as appendiceal mucinous neoplasms, raised concern for a neoplasm, or were thought to exhibit localized pseudomyxoma peritonei. Two cases showed eversion of the appendiceal lining onto the serosa; 1 showed collision between the diverticulum and endosalpingiosis, and 3 had rare nonneoplastic epithelial cells in extra-appendiceal mucin. Most cases showed mucosal hyperplasia, mild crypt disarray, and variable reactive atypia. Eight cases had mucosal neuromas or other neural changes. None of the patients progressed to pseudomyxoma peritonei during the follow-up interval (mean 23 mo). Pathologists should be aware that ruptured appendiceal diverticula may be associated with serosal mucin and even extra-appendiceal epithelium. Failure to distinguish this process from a mucosal neoplasm with rupture may result in unnecessary therapy and cause the patient undue alarm. PMID:19623035

  3. Characterization and Beneficiation Studies of a Low Grade Bauxite Ore

    NASA Astrophysics Data System (ADS)

    Rao, D. S.; Das, B.

    2014-10-01

    A low grade bauxite sample of central India was thoroughly characterized with the help of stereomicroscope, reflected light microscope and electron microscope using QEMSCAN. A few hand picked samples were collected from different places of the mine and were subjected to geochemical characterization studies. The geochemical studies indicated that most of the samples contain high silica and low alumina, except a few which are high grade. Mineralogically the samples consist of bauxite (gibbsite and boehmite), ferruginous mineral phases (goethite and hematite), clay and silicate (quartz), and titanium bearing minerals like rutile and ilmenite. Majority of the gibbsite, boehmite and gibbsitic oolites contain clay, quartz and iron and titanium mineral phases within the sample as inclusions. The sample on an average contains 39.1 % Al2O3 and 12.3 % SiO2, and 20.08 % of Fe2O3. Beneficiation techniques like size classification, sorting, scrubbing, hydrocyclone and magnetic separation were employed to reduce the silica content suitable for Bayer process. The studies indicated that, 50 % by weight with 41 % Al2O3 containing less than 5 % SiO2 could be achieved. The finer sized sample after physical beneficiation still contains high silica due to complex mineralogical associations.

  4. The evolving molecular genetics of low-grade glioma

    PubMed Central

    Venneti, Sriram; Huse, Jason T.

    2015-01-01

    Low-grade gliomas (LGG) constitute grade I and grade II tumors of astrocytic and grade II tumors of oligodendroglial lineage. Although these tumors are typically slow growing, they may be associated with significant morbidity and mortality due to recurrence and malignant progression, even in the setting of optimal resection. LGG in pediatric and adult age groups are currently classified by morphologic criteria. Recent years have heralded a molecular revolution in understanding brain tumors, including LGG. Next generation sequencing has definitively demonstrated that pediatric and adult LGG fundamentally differ in their underlying molecular characteristics, despite being histologically similar. Pediatric LGG show alterations in FGFR1 and BRAF in pilocytic astrocytomas and FGFR1 alterations in diffuse astrocytomas, each converging on the MAP kinase-signaling pathway. Adult LGG are characterized by IDH1/2 mutations and ATRX mutations in astrocytic tumors and IDH1/2 mutations and 1p/19q codeletions in oligodendroglial tumors. TERT promoter mutations are also noted in LGG and are mainly associated with oligodendrogliomas. These findings have considerably refined approaches to classifying these tumors. Moreover, many of the molecular alterations identified in LGG directly impact on prognosis, tumor biology, and the development of novel therapies. PMID:25664944

  5. Dynamic changes of the luminal and mucosa-associated gut microbiota during and after antibiotic therapy with paromomycin.

    PubMed

    Heinsen, Femke-Anouska; Knecht, Henrik; Neulinger, Sven C; Schmitz, Ruth A; Knecht, Carolin; Khbacher, Tanja; Rosenstiel, Philip C; Schreiber, Stefan; Friedrichs, Anette K; Ott, Stephan J

    2015-07-01

    Gut microbiota play a key role in the host's health system. Broad antibiotic therapy is known to disrupt the microbial balance affecting pathogenic as well as host-associated microbes. The aim of the present study was to investigate the influence of antibiotic paromomycin on the luminal and mucosa-associated microbiota at the DNA (abundance) and RNA (potential activity) level as well as to identify possible differences. The influence of antibiotic treatment on intestinal microbiota was investigated in 5 healthy individuals (age range: 20-22years). All participants received the antibiotic paromomycin for 3d. Fecal samples as well as sigmoidal biopsies were collected before and immediately after cessation of antibiotic treatment as well as after a recovery phase of 42d. Compartment- and treatment status-specific indicator operational taxonomic units (OTUs) as well as abundance- and activity-specific patterns were identified by 16S rRNA and 16S rRNA gene amplicon libraries and high-throughput pyrosequencing. Microbial composition of lumen and mucosa were significantly different at the DNA compared to the RNA level. Antibiotic treatment resulted in changes of the microbiota, affecting the luminal and mucosal bacteria in a similar way. Several OTUs were identified as compartment- and/or treatment status-specific. Abundance and activity patterns of some indicator OTUs differed considerably. The study shows fundamental changes in composition of gut microbiota under antibiotic therapy at both the potential activity and the abundance level at different treatment status. It may help to understand the complex processes of gut microbiota changes involved in resilience mechanisms and on development of antibiotic-associated clinical diseases. PMID:26178862

  6. Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ.

    PubMed

    Sundström, Patrik; Ahlmanner, Filip; Akéus, Paulina; Sundquist, Malin; Alsén, Samuel; Yrlid, Ulf; Börjesson, Lars; Sjöling, Åsa; Gustavsson, Bengt; Wong, S B Justin; Quiding-Järbrink, Marianne

    2015-10-01

    Mucosa-associated invariant T (MAIT) cells are innate-like T cells with a conserved TCR α-chain recognizing bacterial metabolites presented on the invariant MHC-related 1 molecule. MAIT cells are present in intestinal tissues and liver, and they rapidly secrete IFN-γ and IL-17 in response to bacterial insult. In colon cancer, IL-17-driven inflammation promotes tumor progression, whereas IFN-γ production is essential for antitumor immunity. Thus, tumor-associated MAIT cells may affect antitumor immune responses by their secreted cytokines. However, the knowledge of MAIT cell presence and function in tumors is virtually absent. In this study, we determined the frequency, phenotype, and functional capacity of MAIT cells in colon adenocarcinomas and unaffected colon lamina propria. Flow cytometric analyses showed significant accumulation of MAIT cells in tumor tissue, irrespective of tumor stage or localization. Colonic MAIT cells displayed an activated memory phenotype and expression of chemokine receptors CCR6 and CCR9. Most MAIT cells in unaffected colon tissues produced IFN-γ, whereas only few produced IL-17. Colonic MAIT cells also produced TNF-α, IL-2, and granzyme B. In the tumors, significantly lower frequencies of IFN-γ-producing MAIT cells were seen, whereas there were no differences in the other cytokines analyzed, and in vitro studies showed that secreted factors from tumor tissue reduced IFN-γ production from MAIT cells. In conclusion, MAIT cells infiltrate colon tumors but their ability to produce IFN-γ is substantially reduced. We suggest that MAIT cells have the capacity to promote local immune responses to tumors, but factors in the tumor microenvironment act to reduce MAIT cell IFN-γ production. PMID:26297765

  7. Current Management of Adult Diffuse Infiltrative Low Grade Gliomas.

    PubMed

    Le Rhun, Emilie; Taillibert, Sophie; Chamberlain, Marc C

    2016-02-01

    Diffuse infiltrative low grade gliomas (LGG) account for approximately 15% of all gliomas. The prognosis of LGG differs between high-risk and low-risk patients notwithstanding varying definitions of what constitutes a high-risk patient. Maximal safe resection optimally is the initial treatment. Surgery that achieves a large volume resection improves both progression-free and overall survival. Based on results of three randomized clinical trials (RCT), radiotherapy (RT) may be deferred in patients with low-risk LGG (defined as age <40years and having undergone a complete resection), although combined chemoradiotherapy has never been prospectively evaluated in the low-risk population. The recent RTOG 9802 RCT established a new standard of care in high-risk patients (defined as age >40years or incomplete resection) by demonstrating a nearly twofold improvement in overall survival with the addition of PCV (procarbazine, CCNU, vincristine) chemotherapy following RT as compared to RT alone. Chemotherapy alone as a treatment of LGG may result in less toxicity than RT; however, this has only been prospectively studied once (EORTC 22033) in high-risk patients. A challenge remains to define when an aggressive treatment improves survival without impacting quality of life (QoL) or neurocognitive function and when an effective treatment can be delayed in order to preserve QoL without impacting survival. Current WHO histopathological classification is poorly predictive of outcome in patients with LGG. The integration of molecular biomarkers with histology will lead to an improved classification that more accurately reflects underlying tumor biology, prognosis, and hopefully best therapy. PMID:26750130

  8. Temozolomide in children with progressive low-grade glioma1

    PubMed Central

    Gururangan, Sridharan; Fisher, Michael J.; Allen, Jeffrey C.; Herndon, James E.; Quinn, Jennifer A.; Reardon, David A.; Vredenburgh, James J.; Desjardins, Annick; Phillips, Peter C.; Watral, Melody A.; Krauser, Jeanne M.; Friedman, Allan H.; Friedman, Henry S.

    2007-01-01

    We conducted a phase II study to assess the efficacy of oral temozolomide (TMZ) in children with progressive low-grade glioma. Thirty eligible patients were enrolled on this study. Median age at enrollment was 10 years (range, 418 years). Eligible patients received TMZ (200 mg/m2 per day) by mouth for five days every four weeks. Patients received a median of nine cycles (range, 212 cycles) of treatment. Best responses in the 26 patients (86%) with optic pathway glioma (OPG)/pilocytic astrocytoma (PA) included partial response in 3 patients (11%), minor response in 1 (4%), stable disease in 10 (38%), and progressive disease in 12 (46%). Only one of four patients with fibrillary astrocytoma had stable disease for 29 months after TMZ. The overall disease stabilization rate in patients with OPG/PA was 54%, and disease control was maintained for a median interval of 34 months. Seventeen of 26 patients had progressive disease either on or off therapy, and three have died of disease. The two-year progression-free and overall survivals in patients with OPG/PA were 49% (95% CI, 30%67%) and 96% (95% CI, 89%100%), respectively. Worst toxicity related to TMZ in all 30 patients included grade 24 thrombocytopenia in seven patients, grade 24 neutropenia in seven, grade 2 skin rash in one, and intratumor hemorrhage in one. TMZ given in this schedule was successful in stabilizing disease in a significant proportion of the patients with OPG/PA, with manageable toxicity. PMID:17347491

  9. Gut microbiota, low-grade inflammation, and metabolic syndrome.

    PubMed

    Chassaing, Benoit; Gewirtz, Andrew T

    2014-01-01

    The intestinal tract is inhabited by a large diverse community of bacteria collectively referred to as the gut microbiota. Alterations in gut microbiota composition are associated with a variety of disease states including obesity, diabetes, and inflammatory bowel disease (IBD). Transplant of microbiota from diseased persons (or mice) to germfree mice transfers some aspects of disease phenotype, indicating that altered microbiota plays a role in disease establishment and manifestation. There are myriad potential mechanisms by which alterations in gut microbiota might promote disease, including increasing energy harvest, production of toxic metabolites, and molecular mimicry of host proteins. However, our research indicates that an overarching mechanism by which an aberrant microbiota negatively impacts health is by driving chronic inflammation. More specifically, we hypothesize that the histopathologically evident gut inflammation that defines IBD is a severe but relatively rare outcome of an altered host-microbiota relationship, while a much more common consequence of such disturbances is "low-grade" inflammation characterized by elevated proinflammatory gene expression that associates with, and may promote, metabolic syndrome. In this context, a variety of chronic inflammatory diseases may stem from inability of the mucosal immune system to properly manage a stable healthy relationship with the gut microbiota. While one's ability to manage their gut microbiota is dictated in part by genetics, it can be markedly influenced by the composition of the microbiota one inherits from their early environment. Moreover, the host-microbiota relationship can be perturbed by instigator bacteria or dietary components, which may prove to play a role in promoting chronic inflammatory disease states. PMID:24285672

  10. Relative survival of patients with supratentorial low-grade gliomas

    PubMed Central

    Smoll, Nicolas R.; Gautschi, Oliver P.; Schatlo, Bawarjan; Schaller, Karl; Weber, Damien C.

    2012-01-01

    We sought to assess the population-based estimates of age-standardized survival among patients with low-grade gliomas (LGG) and to determine the impact of age and time on relative survival (RS). Data from the Surveillance, Epidemiology, and End Results (SEER) program of NCI from 1973 through 2006 were analyzed to assess survival among 5037 patients. Relationships were modeled using Dickman's piecewise constant hazards RS model. The 3- and 10-year age-standardized RS were 67% and 37%, respectively. When analyzed by age group, the 10-year overall survival (OS) and RS for children (age, <16 years), young adults (age, 16–39 years), adults (age, 40–64 years), and older patients (age, ≥65 years) were 86% and 86%, 61% and 62%, 40% and 43%, and 10% and 14%, respectively. The observed difference between OS and RS was larger among older patients (4%) and smallest among children (<1%). Older patients were 30.5 times (excess hazard ratio [eHR]; 95% confidence interval [CI], 20.3–50.0) as likely as young adults to die during the first year and 18.2 times as likely to die during the second year. Adults were 5.3 (eHR; 95% CI, 3.5–8.1) times as likely to die during their first year as young adults. In the remaining years, the observed survival differences were substantially decreased, and the presence of an age-by-follow-up interaction was observed. Survival among older patients with LGG was substantially different from the one computed for young adults and children. Despite the hazards across age groups not being proportional, RS does not provide additional information, compared with OS, in patients with LGG. PMID:22773277

  11. Immunohistochemical analysis of MDM2 and CDK4 distinguishes low-grade osteosarcoma from benign mimics.

    PubMed

    Yoshida, Akihiko; Ushiku, Tetsuo; Motoi, Toru; Shibata, Tatsuhiro; Beppu, Yasuo; Fukayama, Masashi; Tsuda, Hitoshi

    2010-09-01

    Parosteal osteosarcoma and low-grade central osteosarcoma are two types of low-grade osteosarcoma that show similar clinical behaviors, histological features, and genetic background (ie, amplified sequences of 12q13-15, including MDM2 and CDK4). Low-grade osteosarcoma is often confused with benign lesions, and ancillary techniques to enhance diagnostic accuracy have been awaited. This study explores the use of MDM2 and CDK4 immunohistochemistry for the histological diagnosis of low-grade osteosarcoma. We studied 23 cases of low-grade osteosarcoma from 21 patients (parosteal osteosarcoma (n=14), low-grade central osteosarcoma (n=9)) and 40 cases of benign histological mimics (myositis ossificans (n=11), fibrous dysplasia (n=14), osteochondroma (n=6), desmoplastic fibroma (n=1), florid reactive periostitis (n=4), Nora's lesion (n=3), and turret exostosis (n=1)). Low-grade osteosarcoma labeled for MDM2 in 16 cases (70%) and for CDK4 in 20 cases (87%). All low-grade osteosarcomas expressed one or both markers (100%), with 13 cases (57%) expressing both. Staining pattern was diffuse in most cases, and the majority expressed moderate or strong intensity for either antibody. MDM2/CDK4 immunostaining was shown irrespective of low-grade osteosarcoma histological subtype. In contrast, only 1 Nora's lesion out of the 40 miscellaneous benign processes showed immunoreactivity for MDM2 or CDK4. The combination of these two markers thus shows 100% sensitivity and 97.5% specificity for the diagnosis of low-grade osteosarcoma. MDM2 and CDK4 immunostains therefore reliably distinguish low-grade osteosarcoma from benign histological mimics, and their combination may serve as a useful adjunct in this difficult differential diagnosis. PMID:20601938

  12. AMG 319 Lymphoid Malignancy FIH

    ClinicalTrials.gov

    2016-01-20

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  13. Occupation and lymphoid neoplasms.

    PubMed

    La Vecchia, C; Negri, E; D'Avanzo, B; Franceschi, S

    1989-09-01

    The relationship between occupation and exposure to a number of occupational agents and lymphoid neoplasms was investigated in a case-control study of 69 cases of Hodgkin's disease, 153 non-Hodgkin's lymphomas, 110 multiple myelomas and 396 controls admitted for acute diseases to a network of teaching and general hospitals in the greater Milan area. Among the cases, there was a significant excess of individuals ever occupied in agriculture and food processing: the multivariate relative risks (RR) were 2.1 (95% confidence interval, CI = 1.0-3.8) for Hodgkin's disease, 1.9 (95% CI = 1.2-3.0) for non-Hodgkin's lymphomas and 2.0 (95% CI = 1.1-3.5) for multiple myeloma. Significant trends for duration of exposure to herbicides were observed for lymphomas, but the association was stronger for overall occupation in agriculture than with the specific question of herbicide use. History of occupation in the chemical industry was more frequent among Hodgkin's disease (RR = 4.3, 95% CI = 1.4-10.2), and a significant trend in risk was observed between duration of exposure to benzene and other solvents and multiple myeloma. No significant relation was found between any of the lymphoid neoplasms considered and rubber, dye, painting, printing, tanning leather, photography, pharmaceuticals, wood, coal/gas and nuclear industries. PMID:2789947

  14. High-grade pelvic sarcoma after radiation therapy for low-grade endometrial stromal sarcoma

    SciTech Connect

    Chumas, J.C.; Patsner, B.; Mann, W.J. )

    1990-03-01

    A high-grade heterologous pelvic sarcoma arose in a 60-year-old woman 15 years after she received whole-pelvic radiation for a low-grade endometrial stromal sarcoma. This complication must be considered in determining therapy for low-grade endometrial sarcomas, which are usually inherently of indolent biological behavior.

  15. Protein Ubiquitination in Lymphoid Malignancies

    PubMed Central

    Yang, Yibin; Staudt, Louis M.

    2014-01-01

    Summary Human lymphoid malignancies inherit gene expression networks from their normal B-cell counterpart and co-opt them for their own oncogenic purpose, which is usually governed by transcriptional factors and signaling pathways. These transcriptional factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. With a function involved in almost all cellular events, protein ubiquitination plays a role in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here we discuss our current understanding of both proteolytic and nonproteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid-restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers. PMID:25510281

  16. Taking the temperature of low-grade and very low-grade ductile fabrics: equilibrium and disequilibrium mineral assemblages

    NASA Astrophysics Data System (ADS)

    Cao, Shuyun; Neubauer, Franz; Bernroider, Manfred; Genser, Johann

    2013-04-01

    Many ductile shear zones like ductile low-angle normal faults on top of, and oblique-slip faults bordering, metamorphic core complexes exhibit a regular pattern of fabrics which usually show decreasing temperature and pressure conditions during their formation. This is because the presence of rocks with a dominant but different mineralogy results in shear concentration in the rheological weakest layer. These dominant fabric-forming minerals are with decreasing temperature: feldspar at >450 C, quartz at >300 C and calcite <300 C. Fabrics and textures formed at higher temperatures are preserved in microlithons surrounded by micro-shear zones. This allows determine semiquantitively the temperature and pressure of several fabric-forming events within one rock, where generally disequilibrium is present between micro-lithon and surrounding micro-shear zones. We tested this approach using the white mica barometry and chlorite on two shear zones bordering two distinct metamorphic core complexes. The low-grade Rechnitz metamorphic core complex at the eastern termination of the Eastern Alps, which formed within an extensional setting and is surrounded by a contemporaneously formed Neogene sedimentary basin. Microstructural and textural analysis has revealed the co-existence of microstructures ranging from middle-temperatures to low-temperatures, which overprinted deformation features within the Rechnitz metamorphic core complex. Quartz displays abundant evidence for early high-temperature plastic deformation (e.g. dynamic recrystallization, polygonal grains with straight grain boundaries forming 120 triple junctions) (D2). In some cases, preferred orientations of crystallographic axes are missing and white mica was overgrowing the penetrative foliation. These features suggest annealing during subsequent metamorphism and deformation at high temperature conditions. The high-temperature microstructures and textures are in part or entirely altered by subsequent late low-temperature shearing. Certain minerals such as white mica showed extensive grain-size reduction in mylonites and some are completely transformed into extremely fine grains. The later low-temperature deformational overprint during shearing was affected by ductile low-angle normal faulting. According to backscatter electron analysis (BSE), two microfabric types are observed in white mica and chlorite, (1) type I-microlithons, the older generation with coarse-grained white mica and chlorite occurring in the micro-lithons, where chlorite is sometimes associated with white mica, are seemingly in equilibrium with the surrounding mineral assemblage; and (2) type II-micro-shear zones. The sheared generation has very fine-grained sheared bands, which represent mixtures of white mica and chlorite with apparent disequilibrium boundaries. In most cases, the thermometry calculations from the coarse chlorite grains (microfabric type-I) yield a main result ranging from 328 to 376 C. In the microfabric type II, the thermometry results from the sheared chlorite grains yield a temperature ranging from 305 to 132 C. The later temperature is clearly sub-greenschist facies. The lower temperature group is interpreted to result from late-stage hydrothermal overprint, which affected older microfabrics. Chlorite is seemingly accessible to late-stage resetting. Phengitic compositions with high-Si white micas occur in the microfabric type I micro-lithons, however, some phengitic high-Si compositions are also from the micro-shear zone (micro-type II). We note that there is a continuous range of phengitic white mica to nearly pure muscovite. Phengitic white mica is common in all samples of the lower unit together with white mica of lower phengite content. The lower unit experienced, therefore, high-pressure metamorphism, and white mica grains are partly reset to low-pressure white mica indicating decompression. Decompression occurred during shearing and as a result of tectonic exhumation. Detailed microstructural and textural analysis reveals that the movement along the Mou

  17. Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

    MedlinePLUS

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Finasteride Reduces the Risk of Low-Grade Prostate Cancer ... PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the ...

  18. Prospects for production of synthetic liquid fuel from low-grade coal

    NASA Astrophysics Data System (ADS)

    Shevyrev, Sergei; Bogomolov, Aleksandr; Alekssev, Maksim

    2015-01-01

    In the paper, we compare the energy costs of steam and steam-oxygen gasification technologies for production of synthetic liquid fuel. Results of mathematic simulation and experimental studies on gasification of low-grade coal are presented.

  19. Laryngeal Lymphoma: The High and Low Grades of Rare Lymphoma Involvement Sites

    PubMed Central

    Degaetano, James; Farrugia, Eric; Magri, Claude; Refalo, Nicholas; Camilleri, David J.

    2014-01-01

    The larynx is an extremely rare site of involvement by lymphomatous disease. We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management. PMID:25140179

  20. Plasma-enhanced gasification of low-grade coals for compact power plants

    NASA Astrophysics Data System (ADS)

    Uhm, Han S.; Hong, Yong C.; Shin, Dong H.; Lee, Bong J.

    2011-10-01

    A high temperature of a steam torch ensures an efficient gasification of low-grade coals, which is comparable to that of high-grade coals. Therefore, the coal gasification system energized by microwaves can serve as a moderately sized power plant due to its compact and lightweight design. This plasma power plant of low-grade coals would be useful in rural or sparsely populated areas without access to a national power grid.

  1. Plasma-enhanced gasification of low-grade coals for compact power plants

    SciTech Connect

    Uhm, Han S.; Hong, Yong C.; Shin, Dong H.; Lee, Bong J.

    2011-10-15

    A high temperature of a steam torch ensures an efficient gasification of low-grade coals, which is comparable to that of high-grade coals. Therefore, the coal gasification system energized by microwaves can serve as a moderately sized power plant due to its compact and lightweight design. This plasma power plant of low-grade coals would be useful in rural or sparsely populated areas without access to a national power grid.

  2. Subjective Quality of Life in Persons with Low-Grade Glioma and Their Next of Kin

    ERIC Educational Resources Information Center

    Edvardsson, Tanja I.; Ahlstrom, Gerd I.

    2009-01-01

    Patients with low-grade glioma have a longer survival than patients with highly malignant glioma, and for this reason questions of quality of life (QoL) are of particular importance to such patients as well as to their next of kin. No studies have been found in which both adult patients with low-grade glioma and their next of kin have estimated

  3. Thermoelectric energy converter for generation of electricity from low-grade heat

    DOEpatents

    Jayadev, T.S.; Benson, D.K.

    1980-05-27

    A thermoelectric energy conversion device which includes a plurality of thermoelectric elements is described. A hot liquid is supplied to one side of each element and a cold liquid is supplied to the other side of each element. The thermoelectric generator may be utilized to produce power from low-grade heat sources such as ocean thermal gradients, solar ponds, and low-grade geothermal resources. (WHK)

  4. Ectopic lymphoid tissues and local immunity.

    PubMed

    Carragher, Damian M; Rangel-Moreno, Javier; Randall, Troy D

    2008-02-01

    Ectopic or tertiary lymphoid tissues develop at sites of inflammation or infection in peripheral, non-lymphoid organs. These tissues are architecturally similar to conventional secondary lymphoid organs, with separated B and T cell areas, specialized populations of dendritic cells, well-differentiated stromal cells and high endothelial venules. Ectopic lymphoid tissues are often associated with the local pathology that results from chronic infection or chronic inflammation. However, there are also examples in which ectopic lymphoid tissues appear to contribute to local protective immune responses. Here we review how ectopic lymphoid structures develop and function in the context of local immunity and pathology. PMID:18243731

  5. Ectopic lymphoid tissues and local immunity

    PubMed Central

    Carragher, Damian M.; Rangel-Moreno, Javier; Randall, Troy D.

    2008-01-01

    Ectopic or tertiary lymphoid tissues develop at sites of inflammation or infection in peripheral, non-lymphoid organs. These tissues are architecturally similar to conventional secondary lymphoid organs, with separated B and T cell areas, specialized populations of dendritic cells, well-differentiated stromal cells and high endothelial venules. Ectopic lymphoid tissues are often associated with the local pathology that results from chronic infection or chronic inflammation. However, there are also examples in which ectopic lymphoid tissues appear to contribute to local protective immune responses. Here we review how ectopic lymphoid structures develop and function in the context of local immunity and pathology. PMID:18243731

  6. GNAS mutations are not detected in parosteal and low-grade central osteosarcomas.

    PubMed

    Salinas-Souza, Carolina; De Andrea, Carlos; Bihl, Michel; Kovac, Michal; Pillay, Nischalan; Forshew, Tim; Gutteridge, Alice; Ye, Hongtao; Amary, M Fernanda; Tirabosco, Roberto; Toledo, Silvia Regina Caminada; Baumhoer, Daniel; Flanagan, Adrienne M

    2015-10-01

    Parosteal osteosarcoma, low-grade central osteosarcoma, and fibrous dysplasia share similar histological features that may pose a diagnostic challenge. The detection of GNAS mutations in primary bone tumors has been useful in clinical practice for diagnosing fibrous dysplasia. However, the recent report of GNAS mutations being detected in a significant proportion of parosteal osteosarcoma challenges the specificity of this mutation. As the number of cases reported in this study was small we set out to determine if these results could be reproduced. We studied 97 formalin-fixed paraffin-embedded low-grade osteosarcomas from 90 patients including 62 parosteal osteosarcomas, of which MDM2 amplification was detected in 79%, 11 periosteal osteosarcomas and 24 low-grade central osteosarcoma samples. The mutational status of GNAS was analyzed in codons p.R201, p.Q227, and other less common GNAS alterations by bidirectional Sanger sequencing and/or next generation sequencing using the Life Technologies Ion Torrent platform. GNAS mutations were not detected in any of the low-grade osteosarcomas from which informative DNA was extracted. Our findings therefore support prior observations that GNAS mutations are highly specific for fibrous dysplasia and occur rarely, if ever, in parosteal and other low-grade osteosarcomas. PMID:26248895

  7. Delayed osseous metastasis from low-grade endometrial stromal sarcoma: Uncommon occurrence deserving recognition.

    PubMed

    Chow, Louis Tsun Cheung

    2015-10-01

    Despite excellent prognosis, low-grade endometrial stromal sarcoma (ESS) is notorious for late recurrence even in stage I disease. Bone metastases are distinctly rare and only six cases have so far been reported. Two patients presented with back pain due to spinal metastatic low-grade ESS after 15 and 9?years free of disease after resection of the stage 1 primary uterine tumor. Plain radiograph showed an ivory first lumbar vertebra in the first patient and an osteolytic lesion involving the second thoracic vertebra in the second. In both cases, magnetic resonance imaging showed vertebral tumor with intra-spinal extension and spinal cord compression; biopsy confirmed the diagnosis of metastatic low-grade ESS. The first patient received palliative radiotherapy and chemotherapy while the second underwent surgical decompression followed by adjuvant radiotherapy and chemotherapy. The neurologic symptoms in both patients returned 12?months afterwards and progressed relentlessly despite adjuvant chemotherapy and radiotherapy. The first patient developed multiple bone and lung metastasis, culminating in death 44?months after recurrence. While surviving at 24?months from recurrent disease, the second became paraplegic with double incontinence and was wheelchair bound. Delayed osseous metastatic low-grade ESS, although uncommon, deserves recognition given the predilection for spine as the site of involvement. In such a location, where complete surgical removal is notoriously difficult, if not impossible, the prognosis of spinal metastatic low-grade ESS appears grave with considerable morbidity and mortality. PMID:26171849

  8. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

    PubMed Central

    de Punder, Karin; Pruimboom, Leo

    2015-01-01

    Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases. PMID:26029209

  9. Innate lymphoid cells and asthma.

    PubMed

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. PMID:24679467

  10. Concurrent Primary Peritoneal Low-Grade Serous Carcinoma and Endometrial High-Grade Serous Carcinoma

    PubMed Central

    Lockyer, Megan G.; Deavers, Michael T.

    2015-01-01

    A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp. PMID:25760900

  11. The association between low-grade inflammation, iron status and nucleic acid oxidation in the elderly.

    PubMed

    Broedbaek, Kasper; Siersma, Volkert; Andersen, Jon T; Petersen, Morten; Afzal, Shoaib; Hjelvang, Brian; Weimann, Allan; Semba, Richard D; Ferrucci, Luigi; Poulsen, Henrik E

    2011-04-01

    This study applied a case-control approach to investigate the association between low-grade inflammation, defined by high values within the normal range of C-reactive protein (CRP) and interleukin-6 (IL-6), and urinary markers of nucleic acid oxidation. No differences in excretion of urinary markers of nucleic acid oxidation between cases and controls were found and multivariable linear regression analysis showed no association between urinary markers of nucleic acid oxidation and inflammatory markers. Post-hoc multivariable linear regression analysis showed significant associations between nucleic acid oxidation and various iron status markers and especially a close relationship between nucleic acid oxidation and ferritin. This study shows no association between low-grade inflammation and urinary markers of nucleic acid oxidation in a population of elderly Italian people. The results suggest that low-grade inflammation only has a negligible impact on whole body nucleic acid oxidation, whereas iron status seems to be of great importance. PMID:21275071

  12. Innate Lymphoid Cells in Cancer.

    PubMed

    Vallentin, Blandine; Barlogis, Vincent; Piperoglou, Christelle; Cypowyj, Sophie; Zucchini, Nicolas; Chn, Matthieu; Navarro, Florent; Farnarier, Catherine; Vivier, Eric; Vly, Frdric

    2015-10-01

    The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFN?. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples. PMID:26438443

  13. Mortality in Kittens Is Associated with a Shift in Ileum Mucosa-Associated Enterococci from Enterococcus hirae to Biofilm-Forming Enterococcus faecalis and Adherent Escherichia coli

    PubMed Central

    Ghosh, Anuradha; Borst, Luke; Stauffer, Stephen H.; Suyemoto, Mitsu; Moisan, Peter; Zurek, Ludek

    2013-01-01

    Approximately 15% of foster kittens die before 8 weeks of age, with most of these kittens demonstrating clinical signs or postmortem evidence of enteritis. While a specific cause of enteritis is not determined in most cases, these kittens are often empirically administered probiotics that contain enterococci. The enterococci are members of the commensal intestinal microbiota but also can function as opportunistic pathogens. Given the complicated role of enterococci in health and disease, it would be valuable to better understand what constitutes a healthy enterococcal community in these kittens and how this microbiota is impacted by severe illness. In this study, we characterized the ileum mucosa-associated enterococcal community of 50 apparently healthy and 50 terminally ill foster kittens. In healthy kittens, Enterococcus hirae was the most common species of ileum mucosa-associated enterococci and was often observed to adhere extensively to the small intestinal epithelium. These E. hirae isolates generally lacked virulence traits. In contrast, non-E. hirae enterococci, notably Enterococcus faecalis, were more commonly isolated from the ileum mucosa of kittens with terminal illness. Isolates of E. faecalis had numerous virulence traits and multiple antimicrobial resistances. Moreover, the attachment of Escherichia coli to the intestinal epithelium was significantly associated with terminal illness and was not observed in any kitten with adherent E. hirae. These findings identify a significant difference in the species of enterococci cultured from the ileum mucosa of kittens with terminal illness compared to the species cultured from healthy kittens. In contrast to prior case studies that associated enteroadherent E. hirae with diarrhea in young animals, these controlled studies identified E. hirae as more often isolated from healthy kittens and adherence of E. hirae as more common and extensive in healthy kittens than in sick kittens. PMID:23966487

  14. Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38?-Dependent Restraint of NF-?B Signaling.

    PubMed

    Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

    2016-03-01

    The protein kinase p38? mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38? in several different cell types have demonstrated that p38? signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38?. In this study, we show that p38? regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38? gene, we find that p38? serves to limit NF-?B signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38?-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

  15. Low grade astrocytomas in the West of Scotland 1987-96: treatment, outcome, and cognitive functioning

    PubMed Central

    Yule, S; Hide, T; Cranney, M; Simpson, E; Barrett, A

    2001-01-01

    BACKGROUND—Low grade astrocytomas are among the most common central nervous system tumours in children.
AIMS—To identify risk factors for the development of persistent intellectual handicap.
METHODS—The notes of 30 children with histologically proven low grade astrocytoma who presented during the period 1987-96 were reviewed. Thirteen of these children who were diagnosed with intracranial tumours between 1992 and 1996 underwent cognitive assessment one year after the completion of treatment.
RESULTS—Low grade astrocytomas were found in the cerebellum (59%), thalamus (17%), cerebral hemispheres (10%), and the cervical spinal cord (9%). Where possible all patients were treated with gross total resection of the tumour. Symptomatic children with tumours judged to be inoperable underwent biopsy followed by radiotherapy (13%). Three patients developed progressive disease following surgery and underwent repeat surgery and radiotherapy. Survival at a median follow up of 75 months (range 30-131) is 97%. At one year after the completion of treatment persisting cognitive impairment was common. The strongest predictor of IQ scores was the duration of symptoms of increased intracranial pressure preoperatively.
CONCLUSIONS—Although the overall survival rate of children with low grade astrocytoma is excellent, significant long term disability occurs. Early diagnosis is essential to reduce postoperative cognitive morbidity.

 PMID:11124789

  16. Subependymal seeding of low-grade oligodendroglial neoplasms: a case series.

    PubMed

    Nicolasjilwan, Manal; Lopes, M Beatriz; Larner, James; Wintermark, Max; Schiff, David

    2012-05-01

    The CSF dissemination of low-grade glial tumors is a known albeit rare entity. Few cases have been reported in the literature. We describe a unique series of six patients with supratentorial low-grade gliomas who presented to our institution at ages 20-41 years, and developed signal abnormality along the margin of the fourth ventricle without enhancement at variable times during their disease course (0 to 95 months). MR spectroscopy and perfusion-weighted imaging through the region of abnormality in two of these patients were consistent with a low-grade glial tumor. We hypothesize that this finding represents dissemination of the supratentorial low-grade glioma along the ventricular ependyma or through the ventricular CSF. Although the small size of our series does not allow us to draw statistically significant conclusions, this abnormality correlates with progression of the supratentorial disease with or without features of a higher grade malignancy. Additional variables that were present in all six patients include the presence of an oligodendroglial component within the supratentorial tumor, mutated IDH1, and the supratentorial tumor contacting the ventricular margin. All six patients were males. PMID:22311105

  17. Investigation of denitrifying microbe communities within an agricultural drainage system fitted with low-grade weirs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enhancing wetland characteristics in agricultural drainage ditches with the use of low-grade weirs, has been identified as a potential best management practice (BMP) to mitigate nutrient runoff from agriculture landscapes. This study examined microbe community abundance and diversity involved in den...

  18. Aerobic Training Improved Low-Grade Inflammation in Obese Women with Intellectual Disability

    ERIC Educational Resources Information Center

    Ordonez, F. J.; Rosety, M. A.; Camacho, A.; Rosety, I.; Diaz, A. J.; Fornieles, G.; Garcia, N.; Rosety-Rodriguez, M.

    2014-01-01

    Background: Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type

  19. Aerobic Training Improved Low-Grade Inflammation in Obese Women with Intellectual Disability

    ERIC Educational Resources Information Center

    Ordonez, F. J.; Rosety, M. A.; Camacho, A.; Rosety, I.; Diaz, A. J.; Fornieles, G.; Garcia, N.; Rosety-Rodriguez, M.

    2014-01-01

    Background: Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type…

  20. Neurodevelopmental Outcomes of Extremely Low Gestational Age Neonates with Low Grade Periventricular-Intraventricular Hemorrhage

    PubMed Central

    Payne, Allison H.; Hintz, Susan R.; Hibbs, Anna Maria; Walsh, Michele C.; Vohr, Betty R.; Bann, Carla M.; Wilson-Costello, Deanne E.

    2014-01-01

    Objective To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound. Design Longitudinal observational study Setting Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Participants 1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible. Main Exposure Low grade periventricular-intraventricular hemorrhage Outcome Measures Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. Results Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (−3.91, [95% Confidence Interval [CI]: −6.41, −1.42]) and language (−3.19 [−6.19, −0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]). Conclusion At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. PMID:23460139

  1. Biomarker expression in normal fimbriae: Comparison of high- and low-grade serous ovarian carcinoma

    PubMed Central

    XUYIN, ZHANG; JINGXIN, DING; XIANG, TAO; LUOQI, JIA; KEQIN, HUA

    2012-01-01

    The objective of this study was to assess the difference in fimbriae of high- and low-grade ovarian serous carcinoma (OSC). The fimbriae of normal appearance [without serous tubal intraepithelial carcinoma (STIC)] from 28 patients with high-grade OSCs and 24 patients with low-grade OSCs were assessed for the expression of 6 markers [E-cadherin, matrix metalloproteinase-2 (MMP-2), phospho-AKT (pAKT), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and p53] using immunohistochemistry. Sectioning and extensively examining the fimbria (SEE-FIM) was performed to exclude fimbrial involvement for all the cases. The immunostaining levels of pAKT and COX-2 were significantly higher in the fimbriae of normal appearance from high-grade OSCs compared with low-grade OSCs (61 vs. 8% and 71 vs. 21%; P=0.005 and 0.007, respectively). The immunostaining of E-cadherin was significantly higher in the fimbriae of low-grade OSCs compared with high-grade OSCs (83 vs. 21%; P= 0.003). The remaining 3 markers (MMP-2, VEGF and p53) had similar expression in low- and high-grade OSCs (21 vs. 13%; 25 vs. 21%; and 14 vs. 8%; P=0.78, 0.86 and 0.82, respectively). Our results suggest marked biological differences in the behavior of the fimbriae in high- and low-grade OSCs and indicate that proliferation, cell adhesion and the inflammatory microenvironment of fimbriae in high-grade OSCs without STIC had changed prior to p53 mutation. PMID:23162641

  2. Expression of TYMS in lymph node metastasis from low-grade glioma

    PubMed Central

    DING, BINGQIAN; GAO, MING; LI, ZHENJIANG; XU, CHENYANG; FAN, SHAOKANG; HE, WEIYA

    2015-01-01

    The aim of the present study was to investigate the expression of thymidylate synthase (TYMS) in the primary foci and metastatic lymph nodes of low-grade glioma, and to analyze the function of TYMS in the lymph node metastases from low-grade glioma. The study included 93 cases of surgically resected and pathologically confirmed low-grade glioma, form patients treated at Huaihe Hospital of Henan University (Kaifeng, China). The following clinical data was obtained from each patient: Gender, age, subjective symptoms (dizziness, headache, a feeling of pressure in the head, etc.), site of disease, tumor type, pathological stage, degree of differentiation and lymph node involvement. The surgically resected gliomas and dissected cervical lymph nodes were immunohistochemically stained, and DNA was extracted from the tumor and lymph node tissues samples for polymerase chain reaction sequencing and amplification. The expression of TYMS in the primary foci and metastatic lymph nodes of low-grade glioma was examined. Additionally, the association between pathological features and the postoperative survival rate of the patients was analyzed. The primary lesions of all 93 cases exhibited positive TYMS expression and 43/157 (27.39%) lymph nodes exhibited positive TYMS expression. Factors that significantly influenced the postoperative survival rate of the patients, included the metastasis of the cervical lymph nodes (P<0.01), the number of dissected cervical lymph nodes (P<0.01) and the degree of differentiation (P<0.05). The metastasis of the cervical lymph nodes was the only independent risk factor affecting postoperative disease-free survival. The risk of recurrence in patients with metastasis of the cervical lymph nodes was 6.3-fold higher than in those without metastasis (P<0.01). Thus, the results of the present study provide a theoretical basis for accurately predicting the prognosis of patients with low-grade malignant brain glioma, reducing the conjecture involved in selecting postoperative treatment strategies and improving therapeutic efficacy. PMID:26622711

  3. Involution of lymphoid organs in bottlenose dolphins (Tursiops truncatus) from the western Gulf of Mexico: implications for life in an aquatic environment.

    PubMed

    Clark, Lance S; Turner, Jason P; Cowan, Daniel F

    2005-01-01

    Involution of lymphoid tissues in relation to age has not been defined for bottlenose dolphins (Tursiops truncatus). Twenty-five bottlenose dolphins from the coast of Texas and western Louisiana were examined and complete necropsies were performed with histological samples taken of nearly all tissues. Ages ranged from several days to 27 years. The histology of four lymphoid organs-thymus, pharyngeal tonsil, mucosa-associated lymphoid tissue (MALT) of the colon, and anal tonsil-was assessed. Numerical scores were assigned to specific morphological features, thus creating an involution score. Definable and scorable features of each organ were selected for evaluation and determination of loss of lymphoid elements. Neonatal dolphins were recorded as the reference standard for no involution. The highest score for each organ represented the greatest amount of retention of tissue elements. Thus, the lower the score, the greater degree of involution. Comparing involution scores to tooth age permitted an assessment of involution over time. The greatest degree of involution was found in the MALT of the colon. The MALT of the colon declined dramatically so that after age 10 it was absent from 4 of 14 animals and minimally present in 8 others. Thymic tissue also suffered a precipitous drop in volume after about age 5, but was found in animals up to 24 years of age. Involution was moderate and variable in both pharyngeal and anal tonsils. In some animals, these tissues were reduced in volume early, and prominent in others well into adult life (over 20 years). PMID:15622514

  4. Analytical Detection of Immunoglobulin Heavy Chain Gene Rearrangements in Gastric Lymphoid Infiltrates by Peak Area Analysis of the Melting Curve in the LightCycler System

    PubMed Central

    Retamales, Eduardo; Rodriguez, Luis; Guzman, Leda; Aguayo, Francisco; Palma, Mariana; Backhouse, Claudia; Argandona, Jorge; Riquelme, Erick; Corvalan, Alejandro

    2007-01-01

    Because it is difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from chronic gastritis in gastric lymphoid infiltrates, molecular detection of monoclonality through immunoglobulin heavy chain (IgH) gene rearrangements is commonly performed. However, heterogeneity in the performance and results obtained from IgH gene rearrangements has been reported. To improve the accuracy in the diagnosis of gastric lymphoid infiltrates, we developed an analytical approach based on one-peak area analysis of the melting curve in the LightCycler System. Using a training-testing approach, the likelihood ratio method was selected to find a discriminative function of 4.64 in the training set (10 gastric MALT lymphomas and 10 chronic gastritis cases). This discriminative function was validated in the testing set (five gastric MALT lymphomas, six abnormal lymphocytic infiltrates with subsequently demonstrated gastric MALT lymphomas, and six cases of chronic gastritis). All but one case of gastric MALT lymphoma, as well as abnormal lymphocytic infiltrates, clustered under 4.64, and all chronic gastritis cases clustered above 4.64. These results were validated by conventional electrophoreses confirming one or two sharp bands in cases of gastric MALT lymphomas and a smear of multiple bands in cases of chronic gastritis. Analytical detection of IgH gene rearrangement in gastric lymphoid infiltrates by one-peak area analysis correctly distinguishes gastric MALT lymphomas from chronic gastritis, even in cases with diagnosis of abnormal lymphocytic infiltrates. PMID:17591935

  5. Viral-associated lymphoid proliferations?

    PubMed Central

    Pittaluga, Stefania

    2013-01-01

    The histological spectrum of viral-associated lymphoid proliferations is quite broad, ranging from reactive lymphadenitis to atypical proliferations mimicking classical Hodgkin lymphoma or non-Hodgkin lymphoma. Virally associated reactive lesions can appear quite alarming on histological examination, because of direct (cytopathic) and indirect viral-induced changes eliciting a polymorphic cellular host response. In addition, the atypical lymphoid proliferation may show aberrant phenotypic features as well as restricted/clonal gene immunoglobulin or T-cell receptor rearrangements, further complicating the interpretation. In order to achieve an accurate diagnosis, it is important to be aware of the clinical history, including family history and ethnic background, clinical presentation, symptoms, and extent of the disease. Among the clinical data, particular emphasis should be placed on serology and viral load studies, and the use of immunosuppressive drugs. The clinical course and outcome vary greatly, from an indolent, self-limited to aggressive clinical course, blurring at times the distinction between neoplastic and reactive proliferations. It is now recognized that immunosenescence also plays a significant role in the development of these viral-associated lymphoid proliferations, and new entities have been described in recent years. In this review we discuss mostly EpsteinBarr virus-associated viral proliferations that may be confused with lymphomas, which the practicing pathologist may encounter. PMID:23537914

  6. Glycated haemoglobin A1c is associated with low-grade albuminuria in Chinese adults

    PubMed Central

    Huang, Xiaolin; Zhou, Yulin; Xu, Baihui; Sun, Wanwan; Lin, Lin; Sun, Jichao; Xu, Min; Lu, Jieli; Bi, Yufang; Wang, Weiqing; Xu, Yu; Ning, Guang

    2015-01-01

    Background and objective Diabetes is a strong risk factor for cardiovascular diseases, whereas few studies have investigated simultaneously the associations of glycated haemoglobin A1c (HbA1c), fasting blood glucose (fasting plasma glucose (FPG)) and 2 h postload blood glucose (2 h PG) with low-grade albuminuria, which is an earlier marker of cardiovascular diseases in the general population. Our study aimed to investigate and compare associations of HbA1c, FPG, and 2 h PG levels with risks of low-grade albuminuria in the middle-aged and elderly Chinese. Design and methods This was a cross-sectional study involving 9188 participants aged 40 years or older. All participants underwent a standard 75 g oral glucose tolerance test. Low-grade albuminuria was defined as the highest quartile of urinary albumin-to-creatinine ratio (ACR) (>6.10 mg/g in males and >8.76 mg/g in females) in respondents without microalbuminuria or macroalbuminuria. Results HbA1c, FPG and 2 h PG were all significantly correlated with urinary ACR after adjustment for confounders (all p values <0.0001). After adjustment for HbA1c, the relationships of FPG and 2 h PG with ACR reduced to null. HbA1c levels were still significantly associated with ACR after further adjustment for FPG and 2 h PG. Multiple logistic regression showed that risks of low-grade albuminuria were positively associated with HbA1c levels in a dose–response manner. Compared with participants with HbA1c ≤37 mmol/mol (5.5%), ORs (95% CIs) for low-grade albuminuria were 1.05 (0.94 to 1.18), 1.25 (1.04 to 1.50), 1.40 (1.04 to 1.90) and 2.21 (1.61 to 3.03) for HbA1c categories of 38–42 mmol/mol (5.6–6.0%), 43–48 mmol/mol (6.1–6.5%), 49–53 mmol/mol (6.6–7.0%), and >53 mmol/mol (7.0%), respectively (pfor trend <0.0001). Conclusions HbA1c, but not FPG or 2 h PG, was independently associated with an increased risk of low-grade albuminuria in the middle-aged and elderly Chinese. PMID:26243552

  7. The Outlook for Low-Grade Fuels in Tomsk Region: Research Experience at Tomsk Polytechnic University

    NASA Astrophysics Data System (ADS)

    Khaustov, Sergei A.; Kazakov, Alexander V.; Cherkashina, Galina A.; Sobinova, Liubov A.

    2016-02-01

    The urgency of the discussed issue is caused by the need to substitute in the regional fuel-energy balances imported energy resources with local low-grade fuels. The main aim of the study is to estimate thermal properties of local fuels in Tomsk region and evaluate its energy use viability. The methods used in the study were based standard GOST 52911-2008, 11022-95 and 6382-2001, by means of a bomb calorimeter ABK-1 and Vario micro cube analyzer. The mineral ash of researched fuels was studied agreeing with GOST 10538-87. The results state the fact that discussed low-grade fuels of Tomsk region in the unprepared form are not able to replace imported coal in regional energy balance, because of the high moisture and ash content values. A promosing direction of a low-temperature fue processing is a catalytic converter, which allows receiving hydrogen-enriched syngas from the initial solid raw.

  8. Intracranial Undifferentiated Sarcoma Arising from a Low-Grade Glioma: A Case Report and Literature Review

    PubMed Central

    Kim, Bum-Joon; Kim, Jong-Hyun; Chung, Hung-Seob

    2015-01-01

    Undifferentiated sarcomas are rarely identified in the intracranial region. A 23-year-old man was admitted with a chief complaint of headache. Initial magnetic resonance images showed signs of low-grade glioma in the frontal lobe. Stereotactic biopsy was performed, and a diagnosis of diffuse astrocytoma was confirmed. Three months later, the patient presented with a high-grade tumor as seen on imaging studies. He underwent total resection of the tumor and histopathological tests identified an undifferentiated sarcoma. The patient died eight months later due to massive tumor bleeding. To the best of our knowledge, this is the first report of undifferentiated sarcoma arising from low-grade glioma without any chemotherapy or radiotherapy. PMID:26180618

  9. Low-grade adenocarcinoma of endolymphatic sac mimicking jugular paraganglioma at clinical and neuroradiological examination.

    PubMed

    Roncaroli, F; Giangaspero, F; Piana, S; Andreoli, A; Ricci, R

    1997-01-01

    We report a case of low-grade adenocarcinoma of endolymphatic sac origin mimicking jugular paraganglioma at clinical and neuroradiological examination. The lesion occurred in a 72-year-old male who presented with a long-standing history of right-sided hearing loss and a few-week history of progressive facial nerve palsy and right aural pain. At histology, the tumor was composed of pseudoglandular spaces with papillary infoldings. Lumina contained colloid-like material. The lesion was surgically removed with suboccipital approach following endoarterial embolization. This study emphasizes that low-grade adenocarcinomas of endolymphatic sac origin extending to posterior cranial fossa and jugular paraganglioma may be indistinguishable preoperatively at clinical and radiological levels. PMID:9323449

  10. Low-grade osteosarcoma arising from cemento-ossifying fibroma: a case report.

    PubMed

    Lee, Yong Bin; Kim, Nam-Kyoo; Kim, Jae-Young; Kim, Hyung Jun

    2015-02-01

    Cemento-ossifying fibromas are benign tumors, and, although cases of an aggressive type have been reported, no cases of cemento-ossifying fibroma transforming into osteosarcoma have been documented previously. Low-grade osteosarcoma is a rare type of primary bone tumor, representing 1%-2% of all osteosarcomas. A 45-year-old female patient was diagnosed with cemento-ossifying fibroma, treated with mass excision several times over a period of two years and eight months, and followed up. After biopsy gathered because of signs of recurrence, she was diagnosed with low-grade osteosarcoma. The patient underwent wide excision, segmental mandibulectomy, and reconstruction with fibula free flap. The aim of this report is to raise awareness of the possibility that cemento-ossifying fibroma can transform into osteosarcoma and of the consequent necessity for careful diagnosis and treatment planning. PMID:25741469

  11. A new thermal cycle using low grade heat temperature pressure potential amplifier

    SciTech Connect

    Schlichtig, R.C.

    1983-12-01

    The science of thermodynamics, which arose in the 19th century, largely through the genius of Maxwell, directs that greater efficiency is achieved in heat engines with the use of high temperature and thus high grade heat input. Since then nearly all research dealing with heat engines has involved high temperature heat sources whether depletable fuel, nuclear or solar. But we are living in an ocean of renewable low grade heat with small temperature differentials. Choice of research has been to work with such low grade heat sources, following the leads suggested by two hitherto unpublished new principles which were found and incorporated in my Washington State University master's thesis in 1932. After much searching the operation of these principles was found in the case of absorption of refrigerants in certain alcohols. The unique behavior of these fluid solutions made a new thermal cycle possible.

  12. Low-grade sarcoma in classical seminoma - the first case reported

    PubMed Central

    Petersson, Fredrik; Michal, Michal; Grossmann, Petr; Franco, Marcello; Zme?nk, Michal; Hes, Ondrej

    2010-01-01

    A 30-year-old male with no previous history of neoplastic disease presented with a 5 cm large testicular tumor. Routine histopathological examination and immunohistochemical investigation showed a classical seminoma with a contiguous 8 mm large nodule. The nodule was separated from the tunica albuginea by tubuli seminiferi showing intratesticular germ cell neoplasi not otherwise specified (NOS). The nodule was composed of spindle cells with low-grade nuclear atypia, nuclear and cytoplasmic S100 protein immunoreactivity in 15% of the cells and a proliferative activity of up to 20%. No other germ cell tumor components were found. To the best of our knowledge, we herein present the first tumor of a pure classical seminoma with an associated low-grade sarcomatous component. PMID:20126588

  13. Low-grade osteosarcoma arising from cemento-ossifying fibroma: a case report

    PubMed Central

    Lee, Yong Bin; Kim, Nam-Kyoo; Kim, Jae-Young

    2015-01-01

    Cemento-ossifying fibromas are benign tumors, and, although cases of an aggressive type have been reported, no cases of cemento-ossifying fibroma transforming into osteosarcoma have been documented previously. Low-grade osteosarcoma is a rare type of primary bone tumor, representing 1%-2% of all osteosarcomas. A 45-year-old female patient was diagnosed with cemento-ossifying fibroma, treated with mass excision several times over a period of two years and eight months, and followed up. After biopsy gathered because of signs of recurrence, she was diagnosed with low-grade osteosarcoma. The patient underwent wide excision, segmental mandibulectomy, and reconstruction with fibula free flap. The aim of this report is to raise awareness of the possibility that cemento-ossifying fibroma can transform into osteosarcoma and of the consequent necessity for careful diagnosis and treatment planning. PMID:25741469

  14. Low-grade fibromatosis-like spindle cell carcinoma of the breast.

    PubMed

    Dwyer, Jessica B; Clark, Beth Z

    2015-04-01

    Low-grade fibromatosis-like spindle cell carcinoma is a rare tumor in the breast, and represents a variant of the very heterogeneous group of metaplastic carcinomas of the breast. These tumors warrant distinction because of their resemblance to pure fibromatosis, their propensity for local recurrence, and their favorable prognosis among the metaplastic carcinomas of the breast. The diagnosis is potentially challenging, particularly on core needle biopsies, because of the morphologic overlap with other low-grade spindle cell lesions. Recognition of a proliferation of cytologically bland spindle cells with areas of epithelial differentiation in combination with immunohistochemistry using antibodies against cytokeratins and myoepithelial markers should aid in producing a definitive diagnosis. These tumors can be locally aggressive with an increased incidence of local recurrence, but the potential for lymph node or distant metastasis is low. Complete excision with adequate margins is considered curative in the majority of cases. PMID:25822766

  15. High-grade Transformation of Low-grade B-cell Lymphoma: Pathology and Molecular Pathogenesis.

    PubMed

    Agbay, Rose Lou Marie C; Loghavi, Sanam; Medeiros, L Jeffrey; Khoury, Joseph D

    2016-01-01

    Patients with low-grade (clinically indolent) lymphomas are at risk to undergo transformation to high-grade (clinically aggressive) lymphoma, although transformation only occurs in a subset of patients. When transformation occurs it is a critical event that determines the course of disease and is associated with unfavorable patient outcomes. Accurate detection of transformation, predictive biomarkers, and identification of specific molecular pathways implicated in the pathobiology of transformation will facilitate personalized therapeutic approaches and underpin advances in clinical outcomes. In this article, we present an update of the clinical and pathologic diagnostic criteria for low-grade B-cell lymphoma transformation and discuss the molecular alterations involved in the pathogenesis of this biological phenomenon. PMID:26658667

  16. Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

    PubMed Central

    da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, Joo Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

    2013-01-01

    An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

  17. Classification and grading of low-grade astrocytic tumors in children.

    PubMed

    Giannini, C; Scheithauer, B W

    1997-04-01

    This article reviews current perspectives in the classification and grading of astrocytomas in children and calls attention to several histologically distinct groups of low-grade tumors that characteristically arise during childhood. Recognition of these tumors and the range of histological features that they may exhibit is essential for making rational assessments regarding their expected behavior and, more importantly, for guiding therapeutic intervention. For example, pleomorphic xanthoastrocytoma, which may exhibit "anaplastic" features, generally carries a relatively favorable prognosis and should not be classified with other high-grade gliomas, such as anaplastic astrocytoma and glioblastoma multiforme. Similarly, the finding of anaplastic features, such as vascular proliferation or necrosis, in pilocytic astrocytomas does not automatically portend the unfavorable prognosis that such features would imply for "diffuse" astrocytomas. Increased appreciation of the morphological diversity of astrocytomas in children should help to improve the management of children with low-grade astrocytic tumors by avoiding potentially dangerous overtreatment of otherwise indolent lesions. PMID:9161729

  18. Total sacrectomy for low-grade malignant peripheral nerve sheath tumour: a case report.

    PubMed

    Kiatisevi, Piya; Piyaskulkaew, Chaiwat; Sukunthanak, Bhasanan; Thanakit, Voranuch; Bumrungchart, Saraporn

    2014-12-01

    We report on a 58-year-old woman who underwent total sacrectomy and spinopelvic reconstruction for a low-grade malignant peripheral nerve sheath tumour involving the sacrum. One week later, she developed deep wound infection, and the entire spinopelvic reconstruction was removed. At the 36-month followup, the patient had no pain and was able to walk with a walking frame. There was no sign of recurrence or metastasis. PMID:25550028

  19. Platelet Turnover in Stable Coronary Artery Disease Influence of Thrombopoietin and Low-Grade Inflammation

    PubMed Central

    Larsen, Sanne Bjet; Grove, Erik Lerkevang; Hvas, Anne-Mette; Kristensen, Steen Dalby

    2014-01-01

    Background Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD). The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown. Aim To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency. Methods We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio) were determined using automated flow cytometry (Sysmex XE-2100). Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6. Results We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r?=?0.610.99, p<0.0001). Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r?=??0.17?0.25, p<0.0001). Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p?=?0.03) and in smokers (p?=?0.003). Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r?=?0.10, p?=?0.03) and thrombopoietin (r?=?0.16, p<0.001). Also interleukin-6 correlated with thrombopoietin (r?=?0.10, p?=?0.02). Conclusion In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a substantial impact on platelet turnover parameters. PMID:24465602

  20. Low-grade B-cell lymphoma presenting primarily in the bone marrow.

    PubMed

    Iwatani, Kayoko; Takata, Katsuyoshi; Sato, Yasuharu; Miyata-Takata, Tomoko; Iwaki, Noriko; Cui, Wei; Sawada-Kitamura, Seiko; Sonobe, Hiroshi; Tamura, Maiko; Saito, Katsuhiko; Miyatani, Katsuya; Yamasaki, Rie; Yamadori, Ichiro; Fujii, Nobuharu; Terasaki, Yasushi; Maeda, Yoshinobu; Tanimoto, Mitsune; Nakamura, Naoya; Yoshino, Tadashi

    2014-07-01

    Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma. PMID:24767771

  1. Alteration of Lysosome Fusion and Low-grade Inflammation Mediated by Super-low-dose Endotoxin*

    PubMed Central

    Baker, Bianca; Geng, Shuo; Chen, Keqiang; Diao, Na; Yuan, Ruoxi; Xu, Xiguang; Dougherty, Sean; Stephenson, Caroline; Xiong, Huabao; Chu, Hong Wei; Li, Liwu

    2015-01-01

    Subclinical super-low-dose endotoxin LPS is a risk factor for the establishment of low-grade inflammation during the pathogenesis and progression of chronic diseases. However, the underlying mechanisms are not well understood. At the cellular level, a disruption of lysosome fusion with endosomes or autophagosomes may contribute to the potentiation of low-grade inflammation. In this study, we identified that subclinical super-low-dose endotoxin LPS can potently inhibit the process of endosome acidification and lysosome fusion with endosomes or autophagosomes in primary macrophages. Super-low-dose LPS induced the inhibitory phosphorylation of VPS34, thus leading to the disruption of endosome-lysosome fusion. This effect may depend upon the clearance and relocation of Tollip in macrophages by super-low-dose LPS. Consistent with this notion, Tollip-deficient macrophages had constitutively elevated levels of VPS34 inhibitory phosphorylation and constitutive disruption of endosome-lysosome fusion. By employing a skin excision wound-healing model, we observed that Tollip-deficient mice had significantly elevated levels of cell stress and reduced wound repair. This study reveals a novel mechanism responsible for the modulation of endosome-lysosome fusion and low-grade inflammation in innate macrophages. PMID:25586187

  2. Low-grade mucinous neoplasia in a cecal diverticulum: A case report

    PubMed Central

    Nakatani, Kazuyoshi; Tokuhara, Katsuji; Sakaguchi, Tatsuma; Ryota, Hironori; Yoshioka, Kazuhiko; Kon, Masanori

    2015-01-01

    Introduction Low-grade mucinous neoplasia is an uncommon benign tumor that develops in the appendix. The development of mucocele disease has never been reported in a colonic diverticulum. We present a case developing low-grade mucinous neoplasia in a cecal diverticulum. Presentation of case A tumor in the ileocecal region was found during a medical examination of a 66-year-old woman. Three months later, the tumor was still present and the patient developed abdominal pain. Laparoscopic ileocecal resection with D2 lymph node dissection was performed. Histopathological examination revealed a low-grade mucinous neoplasm in a cecal diverticulum. Discussion Colonic mucoceles reportedly originate from the appendix. There are no previous reports of mucocele disease in a colonic diverticulum worldwide. This report reviews and discusses the management of the appendiceal mucoceles. Conclusion The incidence of colonic diverticula has recently begun to increase in Japan. The possibility of a mucocele within a colonic diverticulum should be considered in patients with submucosal colonic tumors. PMID:26318130

  3. Composite hemangioendothelioma and its classification as a low-grade malignancy.

    PubMed

    McNab, Patricia Moody; Quigley, Brian Christopher; Glass, L Frank; Jukic, Drazen M

    2013-06-01

    Hemangioendotheliomas are vascular neoplasms occupying a spectrum of biological potential ranging from benign to low-grade malignancy. Composite hemangioendothelioma (CH) is one of the less commonly encountered variants exhibiting a mixture of elements of other hemangioendothelioma subtypes, such as epithelioid, retiform, and spindle cell. Some authors have identified areas histopathologically equivalent to angiosarcoma within CH, raising the question of the true nature of this neoplasm. Although CH recurs locally, there are only 3 reported cases which metastasized. To date, 26 cases (including the present case) have been described in the literature. Herein, we describe a unique case of CH arising in the background of previous radiation therapy and long-standing lymphedema (classically associated with the development of angiosarcoma-Stewart-Treves syndrome) that harbored higher grade areas but behaved as a low-grade malignant neoplasm. This, in conjunction with the many reported cases of CH-harboring angiosarcoma-like areas, and the occasional association with a history of lymphedema, raises the question of whether this variant of hemangioendothelioma may actually be an angiosarcoma that behaves prognostically better than the conventional type. After careful study of the natural disease progression of the current case and review of the literature, we discuss justification for the continued classification of CH as a low-grade malignancy. PMID:23694827

  4. Influence of cryosurgery on treatment outcome of low-grade chondrosarcoma.

    PubMed

    Ahlmann, Elke R; Menendez, Lawrence R; Fedenko, Alexander N; Learch, Thomas

    2006-10-01

    Successfully managing low-grade chondrosarcomas with margins considered less than wide would minimize the need for extensive reconstruction. We report our experience using cryotherapy as an adjuvant to treat patients with low-grade intracompartmental chondrosarcomas. Ten consecutive patients had intralesional resections including curettage, cryo-surgery, and polymethylmethacrylate application. Eight of these patients required prophylactic skeletal stabilization. We retrospectively reviewed the outcomes for tumor recurrence, disease progression, and complications. The Musculo-skeletal Tumor Society rating scale was used to evaluate functional outcome, and the mean score was 27 points (range, 25-30 points). The mean age of the patients was 54.4 years (range, 29-83 years), and the average followup was 38.5 months (range, 24-60 months). Patients were treated for lesions of the femur (n = 3), humerus (n = 3), scapula (n = 2), tibia (n = 1), and acetabulum (n = 1). There was no evidence of recurrence or metastases. At the latest followup, all patients were well, however, one patient had hardware loosening. In this small group of patients, intralesional resection with adjuvant cryoablation provided an alternative to more radical procedures for low-grade intracompartmental chondrosarcoma. PMID:16788412

  5. Simulation of NOx emission in circulating fluidized beds burning low-grade fuels

    SciTech Connect

    Afsin Gungor

    2009-05-15

    Nitrogen oxides are a major environmental pollutant resulting from combustion. This paper presents a modeling study of pollutant NOx emission resulting from low-grade fuel combustion in a circulating fluidized bed. The simulation model accounts for the axial and radial distribution of NOx emission in a circulating fluidized bed (CFB). The model results are compared with and validated against experimental data both for small-size and industrial-size CFBs that use different types of low-grade fuels given in the literature. The present study proves that CFB combustion demonstrated by both experimental data and model predictions produces low and acceptable levels of NOx emissions resulting from the combustion of low-grade fuels. Developed model can also investigate the effects of different operational parameters on overall NOx emission. As a result of this investigation, both experimental data and model predictions show that NOx emission increases with the bed temperature but decreases with excess air if other parameters are kept unchanged. 37 refs., 5 figs., 5 tabs.

  6. Low-grade endometrial stromal sarcoma with intravenous extension to the heart.

    PubMed

    Gabal, Samia; Ashour, Zeinab; Hamada, Ghada; Aziz, Saied Abdel; Khairy, Hussein; Badawy, Hesham; Hamada, Emad Mahmoud; Saied, Karim

    2009-01-01

    Endometrial stromal sarcoma (ESS) is a rare neoplasm of uterine origin. Intracardiac metastasis from this tumor is extremely infrequent. This report describes a 24-year-old woman from Yemen who had irregular vaginal bleeding shortly after spontaneous abortion. She developed left-lower-limb swelling, diagnosed by duplex scanning and magnetic resonance imaging as deep venous thrombosis in the inferior vena cava (IVC) that extended into the iliac veins on both sides, as well as the left femoral vein and right atrium. She developed acute respiratory distress, from which she recovered after transfer to the intensive care unit. Transesophageal echocardiography showed a large mass occupying the right atrium and ventricle and another mass in the right ventricular outflow tract with areas of cavitations. The tumor appeared to come from the IVC and extended through the right atrium and right ventricle into the pulmonary artery, ending in several digit-like projections. After surgical resection of the intracardiac mass, pathologic examination revealed a low-grade ESS that was confirmed by immunohistochemistry. The patient underwent panhysterectomy and IVC debridement. Pathologic examination revealed infiltrating low-grade endometrial sarcoma invading the myometrium and left adnexa, with intravenous extension into the pelvic veins and the IVC to the right side of the heart. This case shows that despite its well-known good prognostic nature, low-grade ESS may behave as an aggressive malignancy. PMID:19295944

  7. Paravertebral Low-grade Fibromyxoid Sarcoma with Supernumerary Ring Chromosome: Case Report and Literature Review.

    PubMed

    Chien, Yi-Che Chang; Krolyi, Katalin; Kovcs, Ilona

    2016-01-01

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with a deceptively benign histological appearance and low-grade malignant potential which is often mistaken for other reactive or benign lesions. It most frequently harbors balanced t(7;16) translocation, and leads to the fusion of the FUS and CREB3L2 genes which can be detected by cytogenetic methods. Young adults are most commonly affected and it typically arises in the deep proximal extremities or trunk with frequent recurrences. It may metastasize to the lungs several years later. Paravertebral LGFMS is exceedingly rare and only few cases have been published in the literature. In those cases the novel immunohistochemical markers and cytogenetic studies were not performed and morphological mimickers could not be confidently excluded.We present a rare case of paravertebral LGFMS from a 54-years-old male patient, which previously was misdiagnosed as a neurofibroma with subsequent tumor recurrence. The concrete diagnosis was established by using MUC4 immunohistochemical stain and fluorescent in situ hybridization (FISH), which showed diffuse membranous positivity and supernumerary ring chromosome with unbalanced FUS gene rearrangement, respectively. The latter finding is also rare and may cause diagnostic dilemma if one is not aware of such uncommon, but well-documented phenomenon. Differential diagnosis with other low-grade spindle cell tumors will also be discussed along with the literature review. PMID:26927350

  8. 16S rRNA gene-based analysis of mucosa-associated bacterial community and phylogeny in the chicken gastrointestinal tracts: from crops to ceca.

    PubMed

    Gong, Jianhua; Si, Weiduo; Forster, Robert J; Huang, Ruilin; Yu, Hai; Yin, Yulong; Yang, Chengbo; Han, Yanming

    2007-01-01

    Mucosa-associated microbiota from different regions of the gastrointestinal (GI) tract of adult broilers was studied by analysis of 16S rRNA gene sequences. The microbiota mainly comprised Gram-positive bacteria along the GI tract. Fifty-one operational taxonomic units (OTUs) (from 98 clones) were detected in the ceca, as compared with 13 OTUs (from 49 clones) in the crops, 11 OTUs (from 51 clones) in the gizzard, 14 OTUs (from 52 clones) in the duodenum, 12 OTUs (from 50 clones) in the jejunum and nine OTUs (from 50 clones) in the ileum. Ceca were dominantly occupied by clostridia-related sequences (40%) with other abundant sequences being related to Faecalibacterium prausnitzii (14%), Escherichia coli (11%), lactobacilli (7%) and Ruminococcus (6%). Lactobacilli were predominant in the upper GI tract and had the highest diversity in the crop. Both Lactobacillus aviarius and Lactobacillus salivarius were the predominant species among lactobacilli. Candidatus division Arthromitus was also abundant in the jejunum and ileum. PMID:17233749

  9. Early lesions in lymphoid neoplasia

    PubMed Central

    Fend, Falko; Cabecadas, Jos; Gaulard, Philippe; Jaffe, Elaine S.; Kluin, Philip; Kuzu, Isinsu; Peterson, LoAnn; Wotherspoon, Andrew; Sundstrm, Christer

    2013-01-01

    The increasing use of immunophenotypic and molecular techniques on lymphoid tissue samples without obvious involvement by malignant lymphoma has resulted in the increased detection of early lymphoid proliferations, which show some, but not all the criteria necessary for a diagnosis of malignant lymphoma. In most instances, these are incidental findings in asymptomatic individuals, and their biological behaviour is uncertain. In order to better characterize these premalignant conditions and to establish diagnostic criteria, a joint workshop of the European Association for Haematopathology and the Society of Hematopathology was held in Uppsala, Sweden, in September 2010. The panel reviewed and discussed more than 130 submitted cases and reached consensus diagnoses. Cases representing the nodal equivalent of monoclonal B-cell lymphocytosis (MBL) were discussed, as well as the in situ counterparts of follicular lymphoma (FL) and mantle cell lymphoma (MCL), topics that also stimulated discussions concerning the best terminology for these lesions. The workshop also addressed the borderland between reactive hyperplasia, and clonal proliferations such as pediatric marginal zone lymphoma and pediatric FL, which may have very limited capacity for progression. Virus-driven lymphoproliferations in the grey zone between reactive lesions and manifest malignant lymphoma were covered. Finally, early manifestations of T-cell lymphoma, both nodal and extranodal, and their mimics were addressed. This workshop report summarizes the most important conclusions concerning diagnostic features, as well as proposals for terminology and classification of early lymphoproliferations and tries to give some practical guidelines for diagnosis and reporting. PMID:24307917

  10. Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels.

    PubMed

    Dill-McFarland, Kimberly A; Neil, Katie L; Zeng, Austin; Sprenger, Ryan J; Kurtz, Courtney C; Suen, Garret; Carey, Hannah V

    2014-09-01

    The gut microbiota plays important roles in animal nutrition and health. This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. PMID:25130694

  11. Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

    PubMed Central

    Goz, Catherine; Blonski, Marie; Le Maistre, Guillaume; Bauchet, Luc; Dezamis, Edouard; Page, Philippe; Varlet, Pascale; Capelle, Laurent; Devaux, Bertrand; Taillandier, Luc; Duffau, Hugues; Pallud, Johan

    2014-01-01

    Background We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. Methods One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. Results Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 5.46 mm/y. During follow-up (mean, 70 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.819.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.194.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15200.1, respectively). Conclusions The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults. PMID:24847087

  12. Dietary Phthalates and Low-Grade Albuminuria in US Children and Adolescents

    PubMed Central

    Trasande, Leonardo; Sathyanarayana, Sheela

    2014-01-01

    Summary Background Low-grade albuminuria is an indicator of endothelial dysfunction and is associated with an increased risk of cardiovascular disease. A graded level of exposure to bisphenol A was recently identified to be associated with increased risk of low-grade albuminuria in children and adults. Because bisphenol A and phthalates coexist as dietary contaminants, this study investigated whether exposure to phthalates is also associated with low-grade albuminuria. Design, setting, participants, & measurements Data were examined from 667 children who participated in the 20092010 National Health and Nutrition Examination Survey and who had results for urinary phthalate metabolites and albumin excretion. Urinary albumin and creatinine concentrations were measured in a first morning specimen using a solid-phase fluorescent immunoassay and a Roche/Hitachi Modular P Chemistry Analyzer with an enzymatic method, respectively. Phthalate metabolites were analyzed in a separate spot urine sample from each participant, using high-performance liquid chromatography and tandem mass spectroscopy. Results For each (roughly) 3-fold increase in metabolites of di-2-ethylhexylphthalate (a high molecular weight phthalate commonly found in foods), a 0.55 mg/g increase in albumin/creatinine ratio (ACR) was identified (P=0.02), whereas a 1.30-fold odds of a higher ACR quartile was also identified for each (roughly) 3-fold increase (P=0.02). Higher ACR was not identified in relationship to metabolites of lower molecular phthalates commonly found in lotions or shampoos, suggesting specificity. Conclusions Although reverse causation and unmeasured confounders represent alternative explanations, these findings, in conjunction with our earlier data on bisphenol A, indicate that a wide array of environmental toxins may adversely affect albuminuria and potentially increase the risk of cardiovascular disease. In view of the potential long-term health implications of ongoing exposure in this vulnerable subpopulation, our data support both further study and renewed regulatory efforts to limit exposure during childhood. PMID:24178978

  13. Induction of Experimental Endocarditis by Continuous Low-Grade Bacteremia Mimicking Spontaneous Bacteremia in Humans ?

    PubMed Central

    Veloso, T. R.; Amiguet, M.; Rousson, V.; Giddey, M.; Vouillamoz, J.; Moreillon, P.; Entenza, J. M.

    2011-01-01

    Transient high-grade bacteremia following invasive procedures carries a risk of infective endocarditis (IE). This is supported by experimental endocarditis. On the other hand, case-control studies showed that IE could be caused by cumulative exposure to low-grade bacteremia occurring during daily activities. However, no experimental demonstration of this latter possibility exists. This study investigated the infectivity in animals of continuous low-grade bacteremia compared to that of brief high-grade bacteremia. Rats with aortic vegetations were inoculated with Streptococcus intermedius, Streptococcus gordonii or Staphylococcus aureus (strains Newman and P8). Animals were challenged with 103 to 106 CFU. Identical bacterial numbers were given by bolus (1 ml in 1 min) or continuous infusion (0.0017 ml/min over 10 h). Bacteremia was 50 to 1,000 times greater after bolus than during continuous inoculation. Streptococcal bolus inoculation of 105 CFU infected 63 to 100% vegetations compared to 30 to 71% infection after continuous infusion (P > 0.05). When increasing the inoculum to 106 CFU, bolus inoculation infected 100% vegetations and continuous infusion 70 to 100% (P > 0.05). S. aureus bolus injection of 103 CFU infected 46 to 57% valves. This was similar to the 53 to 57% infection rates produced by continuous infusion (P > 0.05). Inoculation of 104 CFU of S. aureus infected 80 to 100% vegetations after bolus and 60 to 75% after continuous infusion (P > 0.05). These results show that high-level bacteremia is not required to induce experimental endocarditis and support the hypothesis that cumulative exposure to low-grade bacteremia represents a genuine risk of IE in humans. PMID:21321073

  14. Induction of experimental endocarditis by continuous low-grade bacteremia mimicking spontaneous bacteremia in humans.

    PubMed

    Veloso, T R; Amiguet, M; Rousson, V; Giddey, M; Vouillamoz, J; Moreillon, P; Entenza, J M

    2011-05-01

    Transient high-grade bacteremia following invasive procedures carries a risk of infective endocarditis (IE). This is supported by experimental endocarditis. On the other hand, case-control studies showed that IE could be caused by cumulative exposure to low-grade bacteremia occurring during daily activities. However, no experimental demonstration of this latter possibility exists. This study investigated the infectivity in animals of continuous low-grade bacteremia compared to that of brief high-grade bacteremia. Rats with aortic vegetations were inoculated with Streptococcus intermedius, Streptococcus gordonii or Staphylococcus aureus (strains Newman and P8). Animals were challenged with 10(3) to 10(6) CFU. Identical bacterial numbers were given by bolus (1 ml in 1 min) or continuous infusion (0.0017 ml/min over 10 h). Bacteremia was 50 to 1,000 times greater after bolus than during continuous inoculation. Streptococcal bolus inoculation of 10(5) CFU infected 63 to 100% vegetations compared to 30 to 71% infection after continuous infusion (P > 0.05). When increasing the inoculum to 10(6) CFU, bolus inoculation infected 100% vegetations and continuous infusion 70 to 100% (P > 0.05). S. aureus bolus injection of 10(3) CFU infected 46 to 57% valves. This was similar to the 53 to 57% infection rates produced by continuous infusion (P > 0.05). Inoculation of 10(4) CFU of S. aureus infected 80 to 100% vegetations after bolus and 60 to 75% after continuous infusion (P > 0.05). These results show that high-level bacteremia is not required to induce experimental endocarditis and support the hypothesis that cumulative exposure to low-grade bacteremia represents a genuine risk of IE in humans. PMID:21321073

  15. The role of secondary cytoreduction in low-grade serous ovarian cancer or peritoneal cancer

    PubMed Central

    Crane, Erin K; Sun, Charlotte C; Ramirez, Pedro T; Schmeler, Kathleen M.; Malpica, Anais; Gershenson, David M

    2016-01-01

    Objectives We sought to determine the benefit of secondary cytoreductive surgery (SCRS) in patients with low-grade serous ovarian or peritoneal carcinoma, and whether cytoreduction to no gross residual disease affects survival. Methods A single institution retrospective chart review was conducted in patients with recurrent low-grade serous carcinoma who underwent SCRS between 1995–2012. Data including demographics, survival, chemotherapy, disease characteristics at the time of surgery, residual disease, and operative complications were collected. Overall survival (OS) and progression-free survival (PFS) were calculated. Kaplan-Meier and log-rank tests were used to examine survival outcomes. Results Forty-one patients met inclusion criteria. The median time between primary tumor debulking and SCRS was 33.2 months. Of 41 eligible patients who underwent SCRS, 32 (78%) had gross residual disease at the completion of secondary surgery. The median PFS for patients with no gross residual disease after SCRS was 60.3 months, compared to 10.7 months for patients with gross residual disease (p=0.008). Median OS from diagnosis for patients with no gross residual disease after SCRS was 167.5 months compared to 88.9 months (p=0.10). Median OS from the time of SCRS for patients with no gross residual disease was 93.6 months compared to 45.8 months (p=0.04). Complications occurred in 61% of patients after SCRS; there were no deaths directly attributable to surgery. Conclusion Our results suggest a benefit to SCRS in patients with recurrent low-grade serous carcinoma. Efforts to maximally cytoreduce patients should be made as patients with no gross residual disease had a better PFS and a trend toward better OS. PMID:25448453

  16. A new thermal cycle using low grade heat temperature pressure potential amplifier

    SciTech Connect

    Schlichtig, R.C.

    1983-12-01

    The science of thermodynamics, which arose in the 19th century, largely through the genius of Maxwell, directs that greater efficiency is achieved in heat engines with the use of high temperature and thus high grade heat input. Since then nearly all research dealing with heat engines has involved high temperature heat sources whether depletable fuel, nuclear or solar. But we are living in an ocean of renewable low grade heat with small temperature differentials. After much searching the operation of these principles was found in the case of absorption of refrigerants in certain alcohols. The unique behavior of these fluid solutions made a new thermal cycle possible.

  17. Fluidized bed combustion of solid organic wastes and low-grade coals: Research and modeling

    SciTech Connect

    Borodulya, V.A.; Dikalenko, V.I.; Palchonok, G.I.; Stanchits, L.K.

    1995-12-31

    Experimental studies were carried out to investigate devolatilization and combustion of single spherical particles of wood, hydrolytic lignin from ethanol production, leather processing sewage sludge, and low-grade Belarusian brown coals in a fluidized bed of sand. A two-phase model of fluidized bed combustion of biowaste is proposed. The model takes into account combustion of both volatiles and char in the bed as well as in the freeboard. Experimentally obtained characteristics of devolatilization and char combustion are used as parameters of the model proposed.

  18. Lymphoid immunohistochemistry of macaque primates.

    PubMed Central

    Ormerod, L D; Osborn, K G; Lowenstine, L J; Meyer, P R; Parker, J W; Smith, R E; Taylor, C R

    1988-01-01

    The immunohistochemical localizations of 53 monoclonal antibodies with specificities expressed in human lymphoid tissue were investigated on lymph node tissues from Macaca mulatta, M. speciosa, and M. fascicularis using immunoperoxidase techniques. Thirty antibodies showed comparative cross-reactivity. The micro-anatomic distribution of these antigens was closely homologous to that observed in man and antigen densities appeared to be similar. A useful monoclonal antibody panel for immunopathological investigations in macaques was, thereby, defined. Of several pan-T antibodies studied, only OKT11(CD2) showed cross-reactivity. A detailed analysis of the immunocyto-architecture of five rhesus lymph nodes was undertaken. Automated flow cytometry of M. mulatta and M. speciosa peripheral blood showed a broadly similar pattern to man. Images Fig. 1 Fig. 2 PMID:3233792

  19. Low-grade osteomyelitis of the fifth metatarsal with possible concomitant Freiberg's disease of the metatarsal head.

    PubMed

    Uslu, Mustafa; Okur, Mesut; Gonen, Ibak

    2012-01-01

    Freiberg's disease, metatarsal avascular necrosis, is most often seen in healthy athletic adolescent girls. Presenting symptoms include vague pain, swelling, and loss of motion in the involved metatarsophalangeal joints. Low-grade osteomyelitis often is difficult to identify. In this case report, we present a 14-year-old girl with low-grade osteomyelitis of the fifth metatarsal accompanied by possible Freiberg's disease in the same metatarsal. PMID:22981237

  20. Mucinous cystic neoplasm of the liver with low grade dysplasia of the liver.

    PubMed

    Pirdopska, T; Terziev, I; Taneva, I; Dimitrova, V

    2014-01-01

    Mucinous cystic neoplasm (MCN) with low grade dysplasia of the liver is rare. It had been previously called hepatobiliary cystadenoma and is seen almost exclusively in women without an associated invasive carcinoma. There are different theories for development of MCN of the liver. One of these is developing from endodermal immature stroma or primary yolk cells implanted during embryogenesis. Another theory refers to the prevalence of hepatic mucinous cystic neoplasm in segment IV, which may support an implant origin because hamartomatous lesions commonly develop in segment IV. The third theory concerns the expression of oestrogen receptor or progesterone receptor in ovarian-like stroma, which also supports a putative role for female hormones in the tumorogenesis. MCN of the liver is a cystic-forming epithelial neoplasm, usually showing no communication with the bile ducts, composed of cuboidal to columnar, variably mucin-producing epithelium, associated with ovarian-type subepithelial stroma. We present a case of MCN with low grade dysplasia of the liver in a young woman whose working surgical diagnosis was Echinococcus cyst. The MCN diagnosis was confirmed with Immunohistochemical study. PMID:25799624

  1. Magnetic Separation and Magnetic Properties of Low-Grade Manganese Carbonate Ore

    NASA Astrophysics Data System (ADS)

    Wu, Y.; Shi, B.; Ge, W.; Yan, C. J.; Yang, X.

    2015-02-01

    The relation between the magnetic separation behavior and magnetic properties of a low-grade manganese ore was analyzed before and after treatment by direct reduction with coal. It was found that raw ore with an initial average grade of 10.39% Mn and consisting of diamagnetic and paramagnetic minerals can be concentrated by high-intensity magnetic separation to produce a salable product with a grade of 22.75% Mn and a recovery of 89.88%. In contrast, direct reduction of the ore results in a new Mn-Fe oxide phase formed with a combination of ferromagnetic and paramagnetic properties, thereby increasing the magnetic susceptibilities of the ore by almost two orders of magnitude. The grade of Mn for the roasted ore could only be concentrated to 15.49% with a recovery of 66.67%. Therefore, it is concluded that the low-grade manganese ores with antiferromagnetic and paramagnetic (or diamagnetic, but not strongly ferromagnetic) properties could be efficiently beneficiated via high-intensity magnetic separation.

  2. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.

    PubMed

    Zhang, Jinghui; Wu, Gang; Miller, Claudia P; Tatevossian, Ruth G; Dalton, James D; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S; Fulton, Lucinda L; Dooling, David J; Vadodaria, Bhavin; Mulder, Heather L; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Baker, Suzanne J; Ellison, David W

    2013-06-01

    The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. PMID:23583981

  3. Simultaneous Purification and Perforation of Low-Grade Si Sources for Lithium-Ion Battery Anode.

    PubMed

    Jin, Yan; Zhang, Su; Zhu, Bin; Tan, Yingling; Hu, Xiaozhen; Zong, Linqi; Zhu, Jia

    2015-11-11

    Silicon is regarded as one of the most promising candidates for lithium-ion battery anodes because of its abundance and high theoretical capacity. Various silicon nanostructures have been heavily investigated to improve electrochemical performance by addressing issues related to structure fracture and unstable solid-electrolyte interphase (SEI). However, to further enable widespread applications, scalable and cost-effective processes need to be developed to produce these nanostructures at large quantity with finely controlled structures and morphologies. In this study, we develop a scalable and low cost process to produce porous silicon directly from low grade silicon through ball-milling and modified metal-assisted chemical etching. The morphology of porous silicon can be drastically changed from porous-network to nanowire-array by adjusting the component in reaction solutions. Meanwhile, this perforation process can also effectively remove the impurities and, therefore, increase Si purity (up to 99.4%) significantly from low-grade and low-cost ferrosilicon (purity of 83.4%) sources. The electrochemical examinations indicate that these porous silicon structures with carbon treatment can deliver a stable capacity of 1287 mAh g(-1) over 100 cycles at a current density of 2 A g(-1). This type of purified porous silicon with finely controlled morphology, produced by a scalable and cost-effective fabrication process, can also serve as promising candidates for many other energy applications, such as thermoelectrics and solar energy conversion devices. PMID:26492222

  4. Low-Grade, Nonintestinal Nonsalivary Sinonasal Adenocarcinoma Associated With an Exophytic Schneiderian Papilloma: A Case Report.

    PubMed

    Blumberg, Jeffrey M; Escobar-Stein, Juliana; Vining, Eugenia M; Prasad, Manju L

    2015-12-01

    Sinonasal adenocarcinoma is a rare tumor of the head and neck accounting for 10% to 20% of all primary malignancies of the nose and paranasal sinuses. There tumors are classified as salivary, intestinal and nonintestinal, nonsalivary. Low-grade nonintestinal nonsalivary are rare tumors whose diagnosis is essentially that of exclusion. Here we present the first case of one such tumor associated with an exophyic Schneiderian papilloma. A 71-year-old retired aerospace engineer presented with a 1-year history of severe nasal obstruction. Endoscopy and compted tomography imaging demonstrated a polypoid lesion occupying his entire right nasal cavity extending into and filling the nasopharynx. Biopsy suggested adenocarcinoma, at least in situ and the patient subsequently underwent complete resection. Pathologic evaluation demonstrated polypoid tumor consistent with a low-grade papillary adenocarcinoma with micropapillary architecture associated with a small amount of residual exophytic Schneiderian papilloma. Immunohistochemistry revealed diffuse expression of CK7, CK 5/6, and S100 protein in tumor cells. Expression of p63 was seen in basal cells only. Tumor cells did not show expression of CK20, CDX2 (intestinal markers), mammaglobin, GATA3 (salivary markers), PAX8, WT1, nor estrogen, progesterone, or androgen receptors confirming its nonintestinal nonsalivary differentiation. PMID:26261100

  5. Low-grade inflammation, diet composition and health: current research evidence and its translation.

    PubMed

    Minihane, Anne M; Vinoy, Sophie; Russell, Wendy R; Baka, Athanasia; Roche, Helen M; Tuohy, Kieran M; Teeling, Jessica L; Blaak, Ellen E; Fenech, Michael; Vauzour, David; McArdle, Harry J; Kremer, Bas H A; Sterkman, Luc; Vafeiadou, Katerina; Benedetti, Massimo Massi; Williams, Christine M; Calder, Philip C

    2015-10-14

    The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims. PMID:26228057

  6. Bioleaching of heavy metals from a low-grade mining ore using Aspergillus niger.

    PubMed

    Mulligan, Catherine N; Kamali, Mahtab; Gibbs, Bernard F

    2004-07-01

    The main concern of this study is to develop a feasible and economical technique to microbially recover metals from oxide low-grade ores. Owing to the significant quantities of metals that are embodied in low-grade ores and mining residues, these are potential viable sources of metals. In addition, they potentially endanger the environment, as the metals they contain may be released to the environment in hazardous form. Hence, mining industries are seeking an efficient, economic technique to handle these ores. Pyrometallurgical and hydrometallurgical techniques are either very expensive, energy intensive or have a negative impact on the environment. For these reasons, biohydrometallurgical techniques are coming into perspective. In this study, by employing Aspergillus niger, the feasibility of recovery of metals from a mining residue is shown. A. niger exhibits good potential in generating a variety of organic acids effective for metal solubilization. Organic acid effectiveness was enhanced when sulfuric acid was added to the medium. Different agricultural wastes such as potato peels were tested. In addition, different auxiliary processes were evaluated in order to either elevate the efficiency or reduce costs. Finally, maximum solubilization of 68%, 46% and 34% were achieved for copper, zinc and nickel, respectively. Also iron co-dissolution was minimized as only 7% removal occurred. PMID:15177728

  7. Filamentous microbial fossil from low-grade metamorphosed basalt in northern Chichibu belt, central Shikoku, Japan

    NASA Astrophysics Data System (ADS)

    Sakakibara, M.; Sugawara, H.; Tsuji, T.; Ikehara, M.

    2014-05-01

    The past two decades have seen the reporting of microbial fossils within ancient oceanic basalts that could be identical to microbes within modern basalts. Here, we present new petrographic, mineralogical, and stable isotopic data for metabasalts containing filamentous structures in a Jurassic accretionary complex within the northern Chichibu Belt of the Yanadani area of central Shikoku, Japan. Mineralized filaments within these rocks are present in interstitial domains filled with calcite, pumpellyite, or quartz, and consist of iron oxide, phengite, and pumpellyite. δ13CPDB values for filament-bearing calcite within these metabasalts vary from -2.49‰ to 0.67‰. A biogenic origin for these filamentous structures is indicated by (1) the geological context of the Yanadani metabasalt, (2) the morphology of the filaments, (3) the carbon isotope composition of carbonates that host the filaments, and (4) the timing of formation of these filaments relative to the timing of low-grade metamorphism in a subduction zone. The putative microorganisms that formed these filaments thrived between eruption (Late Paleozoic) and accretion (Early Jurassic) of the basalt. The data presented here indicate that cryptoendolithic life was present within water-filled vesicles in pre-Jurassic intraplate basalts. The mineralogy of the filaments reflects the low-grade metamorphic recrystallization of authigenic microbial clays similar to those formed by the encrustation of prokaryotes in modern iron-rich environments. These findings suggest that a previously unusual niche for life is present within intraplate volcanic rocks in accretionary complexes.

  8. Tectonic setting of the low-grade metamorphic rocks of the Dabie Orogen, central eastern China

    NASA Astrophysics Data System (ADS)

    Xu, Shutong; Wu, Weiping; Lu, Yiqun; Wang, Dehua

    2012-04-01

    The tectonic setting on both the northern and southern sides of the Dabie Mountains reveals that low-grade metamorphic rocks are important constituents produced by the subduction of the oceanic crust prior to collision between the Sino-Korean and Yangtze cratons. The Zhangbaling Group/Mulanshan schist is a pre-Ordovician oceanic crust. The Sujiahe and Xinyang/Foziling Groups are trench sediments of the Ordovician-Devonian age, and constitute an accretionary prism associated with subduction. The Yangshan coal measures/Meishan Group was a forearc basin sediment of Carboniferous age, and was overthrust by the accretionary prism during collision. The Susong Group is composed of passive continental margin sediments of the Yangtze craton. Backarc basin sediments are postulated to be concealed by Mesozoic-Cenozoic sediments to the north of the Dabie Mountains. High-ultrahigh pressure terrains are exotic tectonic slices exhumed from depths, located between low-grade metamorphic rocks, and disturb the integrity of the earlier subduction orogen. Subduction occurred during the Ordovician to Devonian periods, and collision initiated at the beginning of the Permian.

  9. Scalable Production of Si Nanoparticles Directly from Low Grade Sources for Lithium-Ion Battery Anode.

    PubMed

    Zhu, Bin; Jin, Yan; Tan, Yingling; Zong, Linqi; Hu, Yue; Chen, Lei; Chen, Yanbin; Zhang, Qiao; Zhu, Jia

    2015-09-01

    Silicon, one of the most promising candidates as lithium-ion battery anode, has attracted much attention due to its high theoretical capacity, abundant existence, and mature infrastructure. Recently, Si nanostructures-based lithium-ion battery anode, with sophisticated structure designs and process development, has made significant progress. However, low cost and scalable processes to produce these Si nanostructures remained as a challenge, which limits the widespread applications. Herein, we demonstrate that Si nanoparticles with controlled size can be massively produced directly from low grade Si sources through a scalable high energy mechanical milling process. In addition, we systematically studied Si nanoparticles produced from two major low grade Si sources, metallurgical silicon (?99 wt % Si, $1/kg) and ferrosilicon (?83 wt % Si, $0.6/kg). It is found that nanoparticles produced from ferrosilicon sources contain FeSi2, which can serve as a buffer layer to alleviate the mechanical fractures of volume expansion, whereas nanoparticles from metallurgical Si sources have higher capacity and better kinetic properties because of higher purity and better electronic transport properties. Ferrosilicon nanoparticles and metallurgical Si nanoparticles demonstrate over 100 stable deep cycling after carbon coating with the reversible capacities of 1360 mAh g(-1) and 1205 mAh g(-1), respectively. Therefore, our approach provides a new strategy for cost-effective, energy-efficient, large scale synthesis of functional Si electrode materials. PMID:26258439

  10. Effect of desliming on the magnetic separation of low-grade ferruginous manganese ore

    NASA Astrophysics Data System (ADS)

    Tripathy, Sunil Kumar; Banerjee, P. K.; Suresh, Nikkam

    2015-07-01

    In the present investigation, magnetic separation studies using an induced roll magnetic separator were conducted to beneficiate low-grade ferruginous manganese ore. The feed ore was assayed to contain 22.4% Mn and 35.9% SiO2, with a manganese-to-iron mass ratio (Mn:Fe ratio) of 1.6. This ore was characterized in detail using different techniques, including quantitative evaluation of minerals by scanning electron microscopy, which revealed that the ore is extremely siliceous in nature and that the associated gangue minerals are more or less evenly distributed in almost all of the size fractions in major proportion. Magnetic separation studies were conducted on both the as-received ore fines and the classified fines to enrich their manganese content and Mn:Fe ratio. The results indicated that the efficiency of separation for deslimed fines was better than that for the treated unclassified bulk sample. On the basis of these results, we proposed a process flow sheet for the beneficiation of low-grade manganese ore fines using a Floatex density separator as a pre-concentrator followed by two-stage magnetic separation. The overall recovery of manganese in the final product from the proposed flow sheet is 44.7% with an assay value of 45.8% and the Mn:Fe ratio of 3.1.

  11. Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

    PubMed Central

    Pedersen, Maria; Rinnov, Anders; Andreasen, Anne S.; Møller, Kirsten; Pedersen, Bente K.

    2014-01-01

    Background. Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation. Objective. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. Study Design. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans. Results. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans. Conclusion. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3. PMID:25104880

  12. Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging

    PubMed Central

    Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Mnzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep

    2014-01-01

    SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related sterile inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676

  13. Transforaminal lumbar interbody fusion in symptomatic low-grade isthmic spondylolisthesis.

    PubMed

    Ahsan, M K; Sakeb, N; Rahman, M G; Zaman, N; Karim, R; Jannat, S N

    2014-07-01

    Isthmic spondylolisthesis (IS) is the most common spondylolytic disorders and one of the most common causes of low back pain and sciatica in adolescents and adults. Although the initial management is conservative, surgery is often the ultimate solution. Interbody fusion has been found superior and replaced the gold standard postero-lateral fusion. Transforaminal Lumbar Interbody Fusion (TLIF) has been associated with fewer complications and has become the choice of surgery. This study was done to evaluate the clinical, radiological and functional outcome of TLIF in Low Grade Isthmic Spondylolisthesis (LGIS). The clinical records of 46 consecutive patients within the age range of 31 to 60 years, who had symptomatic unstable Low Grade Isthmic Spondylolisthesis (LGIS) with or without unilateral radiculopathy in Bangabandhu Sheik Mujib Medical University (BSMMU) and private settings, from April 2007 to March 2012 were reviewed with 2 year completed follow-up. Patients were evaluated for pain by Visual Analogue Score (VAS), Disability by Oswestry Disability Index (ODI), radiological fusion by Brantigan and Steffee criteria, reduction of listhesis by Taillard's method and the overall functional outcome by the Macnab's criteria. Pain (Low back and leg), disability, neurological status had highly significant (p<0.001, paired t test) improvement. Forty two (91.30%) cases achieved satisfactory radiological fusion with overall 30% reduction of slip. Satisfactory outcome was reached in 45(97.83%) cases. Transforaminal Lumbar Interbody Fusion results in significant improvement of clinical, radiological and functional debility of symptomatic LGIS in adults. PMID:25178598

  14. An electrochemical system for efficiently harvesting low-grade heat energy.

    PubMed

    Lee, Seok Woo; Yang, Yuan; Lee, Hyun-Wook; Ghasemi, Hadi; Kraemer, Daniel; Chen, Gang; Cui, Yi

    2014-01-01

    Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low figure-of-merit and low-temperature differential. An alternative approach is to explore thermodynamic cycles. Thermogalvanic effect, the dependence of electrode potential on temperature, can construct such cycles. In one cycle, an electrochemical cell is charged at a temperature and then discharged at a different temperature with higher cell voltage, thereby converting heat to electricity. Here we report an electrochemical system using a copper hexacyanoferrate cathode and a Cu/Cu(2+) anode to convert heat into electricity. The electrode materials have low polarization, high charge capacity, moderate temperature coefficients and low specific heat. These features lead to a high heat-to-electricity energy conversion efficiency of 5.7% when cycled between 10 and 60 C, opening a promising way to utilize low-grade heat. PMID:24845707

  15. Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

    PubMed

    Vaquero, J; Zurita, M; Morales, C; Coca, S

    2001-06-01

    The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma. PMID:11478061

  16. Charging-free electrochemical system for harvesting low-grade thermal energy

    PubMed Central

    Yang, Yuan; Lee, Seok Woo; Ghasemi, Hadi; Loomis, James; Li, Xiaobo; Kraemer, Daniel; Zheng, Guangyuan; Cui, Yi; Chen, Gang

    2014-01-01

    Efficient and low-cost systems are needed to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). Thermally regenerative electrochemical cycle (TREC) is an attractive approach which uses the temperature dependence of electrochemical cell voltage to construct a thermodynamic cycle for direct heat-to-electricity conversion. By varying temperature, an electrochemical cell is charged at a lower voltage than discharge, converting thermal energy to electricity. Most TREC systems still require external electricity for charging, which complicates system designs and limits their applications. Here, we demonstrate a charging-free TREC consisting of an inexpensive soluble Fe(CN)63−/4− redox pair and solid Prussian blue particles as active materials for the two electrodes. In this system, the spontaneous directions of the full-cell reaction are opposite at low and high temperatures. Therefore, the two electrochemical processes at both low and high temperatures in a cycle are discharge. Heat-to-electricity conversion efficiency of 2.0% can be reached for the TREC operating between 20 and 60 °C. This charging-free TREC system may have potential application for harvesting low-grade heat from the environment, especially in remote areas. PMID:25404325

  17. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas

    PubMed Central

    Zhang, Jinghui; Wu, Gang; Miller, Claudia P.; Tatevossian, Ruth G.; Dalton, James D.; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A.; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Vadodaria, Bhavin; Mulder, Heather L.; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G.; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J.; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Baker, Suzanne J.; Ellison, David W.

    2013-01-01

    The commonest pediatric brain tumors are low-grade gliomas (LGGs). We utilized whole genome sequencing to discover multiple novel genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24/39 (62%) tumors. Intragenic duplications of the FGFR1 tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes containing TKD-duplicated FGFR1 into brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. TKD-duplicated FGFR1 induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs/LGGNTs. PMID:23583981

  18. An electrochemical system for efficiently harvesting low-grade heat energy

    NASA Astrophysics Data System (ADS)

    Lee, Seok Woo; Yang, Yuan; Lee, Hyun-Wook; Ghasemi, Hadi; Kraemer, Daniel; Chen, Gang; Cui, Yi

    2014-05-01

    Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low figure-of-merit and low-temperature differential. An alternative approach is to explore thermodynamic cycles. Thermogalvanic effect, the dependence of electrode potential on temperature, can construct such cycles. In one cycle, an electrochemical cell is charged at a temperature and then discharged at a different temperature with higher cell voltage, thereby converting heat to electricity. Here we report an electrochemical system using a copper hexacyanoferrate cathode and a Cu/Cu2+ anode to convert heat into electricity. The electrode materials have low polarization, high charge capacity, moderate temperature coefficients and low specific heat. These features lead to a high heat-to-electricity energy conversion efficiency of 5.7% when cycled between 10 and 60?C, opening a promising way to utilize low-grade heat.

  19. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    ClinicalTrials.gov

    2015-12-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  20. Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

    ClinicalTrials.gov

    2013-11-25

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  1. [Molecular targeted therapy in lymphoid leukemias].

    PubMed

    Kojima, Kensuke; Ando, Toshihiko; Kimura, Shinya

    2014-06-01

    Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias. PMID:25016810

  2. Innate lymphoid cells involve in tumorigenesis.

    PubMed

    Tian, Zhiqiang; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing

    2016-01-01

    Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function was recently demonstrated. In this review we discuss whether and how ILCs involve in the tumorigenesis, providing new insights into the mechanisms underlying the particular functions of ILCs as well as the potential targets for tumor intervention. PMID:25604320

  3. Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer

    PubMed Central

    Prorok-Hamon, Maelle; Friswell, Melissa K; Alswied, Abdullah; Roberts, Carol L; Song, Fei; Flanagan, Paul K; Knight, Paul; Codling, Caroline; Marchesi, Julian R; Winstanley, Craig; Hall, Neil; Rhodes, Jonathan M; Campbell, Barry J

    2014-01-01

    Objective Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. Design A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). Results 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin. Conclusions IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity. PMID:23846483

  4. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  5. Investigation of denitrifying microbial communities within an agricultural drainage system fitted with low-grade weirs.

    PubMed

    Baker, Beth H; Kröger, Robert; Brooks, John P; Smith, Renotta K; Prince Czarnecki, Joby M

    2015-12-15

    Enhancing wetland characteristics in agricultural drainage ditches with the use of low-grade weirs, has been identified as a best management practice (BMP) to mitigate nutrient runoff from agriculture landscapes. A major objective of utilizing low-grade weirs as a BMP includes fostering environments suitable for the biogeochemical removal of nitrogen via denitrification. This study examined the spatial resolution of microbial communities involved in denitrification in agricultural drainage systems fitted with low-grade weirs. Appropriate sampling scales of microbial communities were investigated using 16S rRNA and denitrification functional genes nosZ, nirS, and nirK via quantitative polymerase chain reaction (qPCR) and terminal-restriction fragment length polymorphism (T-RFLP) analysis. Genes 16S rRNA, nosZ, and nirS were all successfully detected in soil samples, while nirK was below the detection limit throughout the study. Utilizing a combination of three sampling regimes (management, reach, catchment) was found to be effective in capturing microbial community patterns, as ANOVA results revealed nosZ gene abundance was significantly greater at the management rather than reach scale (p = 0.045; F = 3.311), although, no significant differences were observed in 16S rRNA or nirS between sampling scales (p > 0.05). A Pearson correlation matrix confirmed that 16S rRNA and nosZ gene abundances were positively correlated with soil carbon (C), nitrogen (N), and moisture, while nirS abundance was only positively correlated with soil C and soil moisture. This highlights the potential for wetland-like characteristics to be recovered in agricultural drainage systems, as weir proximity is observed to enhance soil moisture and conditions for N remediation. This study provides the basis for additional investigations of these unique environments in the Mississippi Alluvial Valley and a starting point for adaptive management to enhance agricultural drainage systems for microbial communities towards nutrient remediation goals. PMID:26414296

  6. Total lymphoid irradiation and discordant cardiac xenografts

    SciTech Connect

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. )

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  7. Novel immunotherapies in lymphoid malignancies.

    PubMed

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE()) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

  8. Intrapelvic dissemination of early low-grade endometrioid stromal sarcoma due to electronic morcellation

    PubMed Central

    Choo, Kyoung-Ja; Lee, Hyun Joo; Lee, Tae Sung; Kim, Ju Hyun; Koh, Suk Bong

    2015-01-01

    Endometrioid stromal sarcoma is a rare malignancy that originates from mesenchymal cells. It is classified into low-grade endometrioid stromal sarcoma (LGESS) and high-grade endometrioid stromal sarcoma. Ultrasonographic findings of LGESS resemble those of submucosal myomas, leading to the possible preoperative misdiagnosis of LGESS as uterine leiomyoma. Electronic morcellation during laparoscopic surgery in women with LGESS can result in iatrogenic intraabdominal dissemination and a poorer prognosis. Here, we report a patient with LGESS who underwent a supracervical hysterectomy and electronic morcellation for a presumed myoma in another hospital. Disseminated metastatic lesions of LGESS in the posterior cul-de-sac and rectal serosal surface were absent on primary surgery, but found during reexploration. In conclusion, when LGESS is found incidentally following previous morcellation during laparoscopic surgery for presumed benign uterine disease, we highly recommend surgical reexploration, even when there is no evidence of a metastatic lesion in imaging studies. PMID:26430669

  9. A preliminary report on the rapid fluorimetric determination of uranium in low-grade ores

    USGS Publications Warehouse

    Grimaldi, F.S.; Levine, Harry

    1950-01-01

    A simple and very rapid fluorimetric procedure is described for the determination of uranium in low-grade shale and phosphate ores. The best working range is from 0.001 to about 0.04 percent U. The procedure employs batch extraction of uranium nitrate by ethyl acetate, using aluminum nitrate as the salting agent, prior to the visual fluorimetric estimation. The procedure is especially designed to save reagents; only 9.5 g of aluminum nitrate and 10 ml of ethyl acetate being used for one analysis. The solution of the sample by means of a fusion with NaOH-NaNO3 flux is rapid. After fusion the sample is immediately extracted without removing silica and other hydrolytic precipitates. Aluminum nitrate very effectively ties up fluoride and phosphate, thus eliminating steps required for their removal.

  10. Cryosurgery in aggressive, benign, and low-grade malignant bone tumours.

    PubMed

    Veth, Ren; Schreuder, Bart; van Beem, Herman; Pruszczynski, Maciej; de Rooy, Jacky

    2005-01-01

    Cryosurgery is a method of treatment for various tumours that induces tissue necrosis with ablative intent. It is used in benign, aggressive, and low-grade malignant bone tumours such as chondrosarcoma grade 1. We describe the history of the technique and the issues associated with cryobiology, as well as the indications, technique, complications, and results of cryosurgery. At the University Medical Centre Nijmegen, Netherlands, 302 tumours have been treated by use of cryosurgery with at least 2 years' follow-up. 96-100% of patients were cured-the response depended on tumour type. Comparison of functional results with data from studies shows that these results concur with other studies on cryosurgery, and are at least equal to results of marginal excision and mostly better than those of wide excisions of grade 1 chondrosarcomas. Thus from an oncological point of view, cryosurgery combined with intralesional excision is equal to marginal excision. PMID:15629273

  11. Roles of Chronic Low-Grade Inflammation in the Development of Ectopic Fat Deposition

    PubMed Central

    Mei, Mei; Yang, Shumin; Li, Qifu

    2014-01-01

    Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders. PMID:25143667

  12. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments

    PubMed Central

    Rud, Roberta; Bello, Lorenzo; Duffau, Hugues; Soffietti, Riccardo

    2012-01-01

    Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy. PMID:23095831

  13. Study of Supercritical Carbon Dioxide Power Cycle for Low Grade Heat Conversion

    SciTech Connect

    Vidhi, Rachana; Goswami, Yogi D.; Chen, Huijuan; Stefanakos, Elias; Kuravi, Sarada; Sabau, Adrian S

    2011-01-01

    Research on supercritical carbon dioxide power cycles has been mainly focused on high temperature applications, such as Brayton cycle in a nuclear power plant. This paper conducts a comprehensive study on the feasibility of a CO2-based supercritical power cycle for low-grade heat conversion. Energy and exergy analyses of the cycle were conducted to discuss the obstacles as well as the potentials of using supercritical carbon dioxide as the working fluid for supercritical Rankine cycle, Carbon dioxide has desirable qualities such as low critical temperature, stability, little environmental impact and low cost. However, the low critical temperature might be a disadvantage for the condensation process. Comparison between a carbon dioxide-based supercritical Rankine cycle and an organic fluid-based supercritical Rankine cycle showed that the former needs higher pressure to achieve the same efficiency and a heat recovery system is necessary to desuperheat the turbine exhaust and pre-heat the pressure charged liquid.

  14. Holocord low grade astrocytoma--Role of radical irradiation and chemotherapy.

    PubMed

    Goyal, Shikha; Puri, Tarun; Julka, P K

    2015-06-01

    Spinal intradural tumors, especially those extending along the entire length of the spinal cord, termed as 'holocord' tumors are uncommon. Most of these are gliomas, with astrocytomas (low grade) predominating in children and ependymomas in adults. Other histologies, though reported, are even rarer. Management is debatable, with both surgery and radiotherapy of such extensive tumors posing challenges. We describe a case of a 14-year-old girl with holocord astrocytoma extending from cervicomedullary junction till lumbar spine, who recovered full neurological function following radical irradiation of entire spine followed by temozolomide-based chemotherapy. No grade 3/4 bone marrow morbidity was seen. Five years following treatment, she maintained normal neurological function and apparently normal pubertal and skeletal growth despite residual disease visible on imaging. Literature review of existing reports of holocord astrocytomas highlighting management and outcome is presented. PMID:25708303

  15. A Rare Pathology: Low-Grade Fibromyxoid Sarcoma of the Maxilla.

    PubMed

    Spalthoff, Simon; Bredt, Martin; Gellrich, Nils-Claudius; Jehn, Philipp

    2016-01-01

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a benign histologic appearance and fully malignant behavior. To date, only 5 cases of LGFMS in the maxillofacial region have been reported. This report describes the case of a 16-year-old boy who was referred to the authors' hospital with an intraosseous myxofibroblastic tumor, probably of the LGFMS type, of the right maxilla. Radical resection with wide safe margins and secondary reconstruction with a free forearm flap were performed. Six-month follow-up showed no sign of recurrence or metastasis. The authors review the scientific literature and discuss different tumor locations and treatment strategies for those in the maxillofacial region. The present case is the sixth reported case of LGFMS in the maxillofacial region (intraosseous LGFMS of the maxilla), adding another facet to the literature regarding this rare soft tissue tumor. PMID:26455471

  16. Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

    PubMed Central

    Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

    2008-01-01

    Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

  17. New Strategies in Pediatric Gliomas: Molecular Advances in Pediatric Low-Grade Gliomas as a Model

    PubMed Central

    Raabe, Eric; Kieran, Mark W.; Cohen, Kenneth J.

    2015-01-01

    Pediatric low-grade gliomas (pLGG) account for more brain tumors in children than any other histologic subtype. While surgery, chemotherapy and radiation remain the mainstay of upfront treatment, recent advances in molecular interrogation of pLGG have shown a small number of recurring genetic mutations in these tumors that might be exploited therapeutically. Notable findings include abnormalities in the RAS/MAP kinase pathway such as NF-1 loss or BRAF activation and mTOR activation. Recent identification of activating re-arrangements in c-MYB and MYBL1 in pediatric diffuse astrocytoma also provide candidates for therapeutic intervention. Targeting these molecularly identified pathways may allow for improved outcomes for patients as pediatric oncology moves into the era of biology-driven medicine. PMID:23881924

  18. Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix

    PubMed Central

    Levine, Edward A; Votanopoulos, Konstantinos I; Qasem, Shadi A; Philip, John; Cummins, Kathleen A; Chou, Jeff W; Ruiz, Jimmy; D’Agostino, Ralph; Shen, Perry; Miller, Lance D

    2016-01-01

    BACKGROUND Appendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. STUDY DESIGN Gene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes. RESULTS Unsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease-specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low-grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age. CONCLUSIONS The 139-gene cassette can have actionable clinical utility for identifying low-grade appendiceal tumor molecular subtypes predictive of therapeutic efficacy of CRS/HIPEC. PMID:26821970

  19. The case for endoscopic treatment of non-dysplastic and low-grade dysplastic Barrett's esophagus.

    PubMed

    Fleischer, David E; Odze, Robert; Overholt, Bergein F; Carroll, John; Chang, Kenneth J; Das, Ananya; Goldblum, John; Miller, Daniel; Lightdale, Charles J; Peters, Jeffrey; Rothstein, Richard; Sharma, Virender K; Smith, Daniel; Velanovich, Victor; Wolfsen, Herbert; Triadafilopoulos, George

    2010-07-01

    Non-dysplastic mucosa (ND-) in Barrett's esophagus (BE) shows clonal molecular aberrations, loss of cell cycle control, and other features of "neoplasia." These changes occur prior to morphologic expression of neoplasia (dysplasia). Morphologic evaluation of dysplasia is fraught with error, and, as a result, often leads to false-negative and false-positive diagnoses. Early "crypt dysplasia" is difficult to detect, and is often missed in routine biopsy specimens. Some studies show substantial progression rates of low-grade dysplasia (LGD), and crypt dysplasia, to esophageal adenocarcinoma (EAC). Dysplasia, even when fully developed, may, in certain circumstances, be difficult to differentiate from non-dysplastic (regenerating) BE. Radiofrequency ablation (RFA) is a safe and effective method for removing mucosa at risk of cancer. Given the difficulties of dysplasia assessment in mucosal biopsies, and the molecular characteristics of ND-BE, this technique should be considered for treatment of all BE patients, including those with ND or LGD. Post-ablation neo-squamous epithelium reveals no molecular abnormalities, and is biologically stable. Given that prospective randomized controlled trials of ablative therapy for ND-BE aiming at reducing EAC incidence and mortality are unlikely to be completed in the near future, endoscopic ablation is a valid management option. The success of RFA in achieving safe, uniform, reliable, and predictable elimination of BE allows surgeons to combine fundoplication with RFA. Currently, there is no type of treatment for dysplastic or non-dysplastic BE that achieves a complete response in 100% of patients, eliminates all risk of developing cancer, results in zero adverse events, is less expensive in terms of absolute costs than surveillance, is durable for 20+ years, or eliminates the need for surveillance. Regardless, RFA shows established safety, efficacy, durability, and cost-effective profiles that should be considered in the management of patients with non-dysplastic or low-grade dysplastic BE. PMID:20405211

  20. Low-grade coals: a review of some prospective upgrading technologies

    SciTech Connect

    Hassan Katalambula; Rajender Gupta

    2009-07-15

    There is a growing need of using low-grade coals because of higher quest for power generation. In the present carbon-constrained environment, there is a need of upgrading these coals in terms of moisture, ash, and/or other trace elements. The current paper reviews technologies used mainly categorized as drying for reducing moisture and cleaning the coal for reducing mineral content of coal and related harmful constituents, such as sulfur and mercury. The earliest upgrading of high-moisture lignite involved drying and manufacturing of briquettes. Drying technologies consist of both evaporative and non-evaporative (dewatering) types. The conventional coal cleaning used density separation in water medium. However, with water being a very important resource, conservation of water is pushing toward the development of dry cleaning of coal. There are also highly advanced coal-cleaning technologies that produce ultra-clean coals and produce coals with less than 0.1% of ash. The paper discusses some of the promising upgrading technologies aimed at improving these coals in terms of their moisture, ash, and other pollutant components. It also attempts to present the current status of the technologies in terms of development toward commercialization and highlights on problems encountered. It is obvious that still the upgrading goal has not been realized adequately. It can therefore be concluded that, because reserves for low-grade coals are quite plentiful, it is important to intensify efforts that will make these coals usable in an acceptable manner in terms of energy efficiency and environmental protection. 68 refs., 7 figs.

  1. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.

    PubMed

    Hunter, Sally M; Anglesio, Michael S; Ryland, Georgina L; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M; Doyle, Maria A; Li, Jason; Gilks, C Blake; Moss, Phillip; Allan, Prue E; Stephens, Andrew N; Huntsman, David G; deFazio, Anna; Bowtell, David D; Gorringe, Kylie L; Campbell, Ian G

    2015-11-10

    Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors. PMID:26506417

  2. Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes

    PubMed Central

    Hunter, Sally M.; Anglesio, Michael S.; Ryland, Georgina L.; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M.; Doyle, Maria A.; Li, Jason; Gilks, C. Blake; Moss, Phillip; Allan, Prue E.; Stephens, Andrew N.; Huntsman, David G.; deFazio, Anna; Bowtell, David D.

    2015-01-01

    Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors. PMID:26506417

  3. Effects of walking on low-grade inflammation and their implications for Type 2 Diabetes

    PubMed Central

    Morettini, Micaela; Storm, Fabio; Sacchetti, Massimo; Cappozzo, Aurelio; Mazz, Claudia

    2015-01-01

    Objective Inflammatory cytokines released by hypertrophic adipocytes contribute to low-grade inflammation, a characteristic of Type 2 Diabetes. Skeletal muscle contraction during physical activity stimulates the secretion of anti-inflammatory cytokines able to counteract this inflammatory status. The aim of this study was to review the evidence of the effectiveness of walking as a physical activity intervention to reduce inflammation. The interplay between adipose tissue and skeletal muscle contributions was also investigated. Method A structured literature review of papers available up to December 2014 was carried out within the PubMed, Scopus and ISI Web of Science databases using the keywords walking and inflammation in order to identify the studies involving healthy subjects and subjects diagnosed with, or at increased risk of, Type 2 Diabetes. Results Thirty-two studies were reviewed, five investigating the acute effects of walking and twenty-seven its chronic effects (n=21 interventional and n=6 observational). Acute effects of walking bouts led to an increase of interleukin-6 in one study, although without any increase in the concentration of the anti-inflammatory marker interleukin-1 receptor antagonist. Eight interventional studies showed a significant reduction of inflammation. A reduction in tumour necrosis factor-? concentration was often associated with an adiposity reduction. The observational studies showed that individuals who walk more present a lower inflammatory status. Conclusion There is no consensus regarding the efficacy of walking in the reduction of low-grade systemic inflammation, even though a relationship cannot be excluded. In each walking bout, no anti-inflammatory effect due to the IL-6-stimulated myokine cascade can be demonstrated. PMID:26844115

  4. Adhesive capsulitis: An age related symptom of metabolic syndrome and chronic low-grade inflammation?

    PubMed

    Pietrzak, Max

    2016-03-01

    Adhesive capsulitis (AC) is very poorly understood, particularly it's underlying etiology. Obesity and metabolic syndrome, which are strongly associated with chronic low grade inflammation, are becoming increasingly understood to underlie a raft of morbid states including upper limb pain syndromes, diabetes (DM), cardiovascular disease (CVD), cancer and central nervous system dysfunction and degeneration. Notwithstanding age, two of the strongest established risk factors for AC are DM and CVD. The hypothesis argues that similar to DM and CVD, the inflammation and capsular fibrosis seen in AC is precipitated by metabolic syndrome and chronic low grade inflammation. These pathophysiological mechanisms are highly likely to be perpetuated by upregulation of pro-inflammatory cytokine production, sympathetic dominance of autonomic balance, and neuro-immune activation. The hypothesis predicts and describes how these processes may etiologically underpin and induce each sub-classification of AC. An improved understanding of the etiology of AC may lead to more accurate diagnosis, improved management, treatment outcomes, and reduce or prevent pain, disability and suffering associated with the disease. The paper follows on with a discussion of similarities between the pathophysiology of AC to general systemic inflammatory control mechanisms whereby connective tissue (CT) fibrosis is induced as a storage depot for leukocytes and chronic inflammatory cells. The potential role of hyaluronic acid (HA), the primary component of the extracellular matrix (ECM) and CT, in the pathophysiology of AC is also discussed with potential treatment implications. Lastly, a biochemical link between physical and mental health through the ECM is described and the concept of a periventricular-limbic central driver of CT dysfunction is introduced. PMID:26880627

  5. Cytology of low-grade cribriform cystadenocarcinoma in salivary glands: Cytological and immunohistochemical distinctions from other salivary gland neoplasms.

    PubMed

    Ohta, Yoshiki; Hirota, Yuko; Kohno, Yohko; Kishimoto, Koji; Norose, Tomoko; Ohike, Nobuyuki; Takimoto, Masafumi; Shiokawa, Akira; Ota, Hidekazu

    2016-03-01

    Low-grade cribriform cystadenocarcinoma of the parotid gland is rare malignancy that is classified as a variant of cystadenocarcinoma. In routine cytologic slides from fine-needle aspiration of a parotid gland, we found several pseudopapillary clusters comprising mucus-producing cells. They included a few tumor cells having three-dimensional nuclear atypia and slight hyperchromatism, although most of the tumor cells showed bland nuclei. Our initial cytological diagnosis was: "Indeterminate. Uncertain whether cystadenocarcinoma or cystadenoma." The subsequent histological diagnosis was low-grade cribriform cystadenocarcinoma. Immunohistochemical staining showed diffuse and strong reactivity for S-100; tumor nests that were rimmed by p63(+) cells, which suggests intraductal proliferation. Here, we report cytomorphological findings of this case, and discuss cytological and immunohistochemical distinctions between low-grade cribriform cystadenocarcinoma and other salivary gland tumors, including a review of the literature. Diagn. Cytopathol. 2016;44:241-245. 2015 Wiley Periodicals, Inc. PMID:26875597

  6. Polyphenol intake is associated with low-grade inflammation, using a novel data analysis from the Moli-sani study.

    PubMed

    Pounis, George; Bonaccio, Marialaura; Di Castelnuovo, Augusto; Costanzo, Simona; de Curtis, Amalia; Persichillo, Mariarosaria; Sieri, Sabina; Donati, Maria Benedetta; Cerletti, Chiara; de Gaetano, Giovanni; Iacoviello, Licia

    2016-01-27

    The association of polyphenol content of human diet with low-grade inflammation is not yet fully understood. It was the objective of this study to evaluate the association of flavonoid and lignan intake with frequently used and easily applicable in clinical practice low-grade inflammation biomarkers, in a novel holistic approach. A total of 5,948 women and 5,965 men (aged ??35years) were analysed from the Moli-sani cohort, randomly recruited from the general population. The EPIC-FFQ was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated using Eurofir eBASIS and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of diet in these nutrients. CRP levels, WBC and PLT count and granulocyte to lymphocyte ratio were conceived as low-grade inflammation biomarkers. INFLA-score was constructed summarizing synergistic effects of these biomarkers. The INFLA-score was negatively associated with PAC-score in different levels of adjustment, in both genders (for all ?-coeflow-grade inflammation status (i.?e. higher quartile of INFLA-score) in men and women (odds ratio [ORs] 0.92 to 0.95, plow-grade inflammation biomarkers in a large population based study. For the first time low-grade inflammation was evaluated in a holistic way through INFLA-score and was associated with polyphenol content of diet. PMID:26355794

  7. Aggressive behavior of low-grade Ta papillary urothelial bladder neoplasm in a 17-year-old patient.

    PubMed

    Labanaris, Apostolos P; Labanaris, Panagiotis G; Gitsos, Giorgos; Khn, Reinhard; Schott, Ghnter E; Zugor, Vahudin

    2007-05-01

    Bladder tumors rarely occur in the first two decades of life, and, in contrast to the cases in adults, 97% of transitional cell carcinomas of the bladder in childhood are low grade, superficial, and of good prognosis, with a progression rate of only 2% to 4%. This report presents a case of low-grade bladder cancer in a 17-year-old patient which behaved quite aggressively. The most striking features of this case included the histopathologic findings and rapid disease progression, despite treatment with agents known for their efficacy against tumors of epithelial and mesenchymal origin. PMID:17482953

  8. O8.03LOW GRADE DIFFUSE ASTROCYTOMA - PROGNOSTIC FACTORS TO ANAPLASTIC TRANSFORMATION

    PubMed Central

    Izquierdo, C.; Majos, C.; Sim, M.; Lucas, A.; Maci, M.; Plans, G.; Gil, M.; Velasco, R.; Bruna, J.

    2014-01-01

    INTRODUCTION: Low grade gliomas (LGG) comprise nearly 20% of all central nervous system (CNS) glial tumors. LGG are characterized by their infiltrative growth and frequent tumor recurrence with malignant progression. They have a heterogeneous clinical behavior being histological, first line resection, velocity of diameter tumor expansion during pretherapeutic period,tumor volume, contrast enhancement and patients' characteritics the only described factors for identifying patients at risk of progression. The identification and validation of new imaging prognostic factors would help to minimize potential treatment-related side effects in LGG. OBJECTIVE: The aim of our study was to analyze the impact of clinical (gender, age, first symptom), histological (gemistocytic) and neuroimaging (tumor growth ratio at 6 months- GR6m) factors on malignant progression in a cohort of diffuse low grade astrocytomas. We conducted serial volumetric analysis using Flair sequences. The time to malignant progression (TMP) was defined as time between histological diagnose and first MRI showing contrast enhancement or histology proven progression. RESULTS: Patients' mean age was 42.5 14.6 years with a male:female ratio of 1.7:1. Median Pignatti index (PI) was 2 (1-4). The median TMP was of 4.76 (0.33-11.8) years. Nearly half (48.2%) of the patients showed a malignant progression. This group had a higher GR6m (49% versus 3%, p = 0.032). A cut-point of GR6m < 2% obtained by ROC analysis showed a sensitivity and specificity of 92.3% and 71% (p = 0.001). In the multivariate analysis the GR6m < 2% (HR: 5.23, 95% CI (1.4-19.61), P = 0.014), gemistocytic component (HR 8, 95% CI (1.6-39.3), p = 0.01) and a PI of 3-4 (HR : 6.94, 95% CI (1.64-29.4), p = 0.008) were identified as independent predictors of TMP. CONCLUSIONS: GR6m resulted as independent prognostic factor of TMP. In addition, our study confirmed PI and gemystocitic histology as prognostic factors on TMP.It is important to define new prognostic factors to anaplastic transformation due to individualized treatment in patients.

  9. Vitamin D, Low-Grade Inflammation and Cardiovascular Risk in Young Children: A Pilot Study.

    PubMed

    Singh, Jasmine; Merrill, Eric Dean; Sandesara, Pratik B; Schoeneberg, Laura; Dai, Hongying; Raghuveer, Geetha

    2015-10-01

    Vitamin D has anti-inflammatory properties, and deficiency is prevalent in children. There is a paucity of data regarding vitamin D status and its correlation with low-grade inflammation and vasculature. We prospectively enrolled 25 children, 9-11 years old (13 male); 21 obese. Eight atherosclerosis-promoting risk factors were scored as categorical variables with the following thresholds defining abnormality: body mass index Z score ? 1.5; systolic blood pressure ? 95th percentile (for age, sex, and height); triglyceride ? 100 mg/dL; low-density lipoprotein cholesterol (LDL-C) ? 110 mg/dL; high-density lipoprotein cholesterol ? 45 mg/dL; hemoglobin A1C (HBA1C) ? 5.5; 25-hydroxyvitamin D [25(OH) D] ? 30 ng/mL, and tobacco smoke exposure. High-sensitivity C-reactive protein (hsCRP) was measured to assess low-grade inflammation and classified as low- (<1 mg/L), average- (1-3 mg/L), and high-risk (>3 to <10 mg/L) groups. The proportion of children within each hsCRP group who had above threshold risk factors was calculated. Carotid artery ultrasound was performed to measure carotid artery intima-media thickness (CIMT). Median (range) for 25(OH) D was 24 (17-45) ng/mL. Eighteen were either 25 (OH) D deficient (<20 ng/mL) or insufficient (20-30 ng/mL), and seven were sufficient (>30 ng/mL). hsCRP was 1.7 (0.2-9.1) mg/L, with 11 being <1.0 mg/L, 8 between 1.0-3.0 and 6 > 3.0 to < 10.0 mg/L. Risk factor score was 3.9 1.7 out of eight. 25(OH) D levels did not correlate with hsCRP or CIMT. While vitamin D deficiency, inflammation, and risk factors coexist at a very young age, causative mechanisms remain unclear. PMID:25832850

  10. The behavior of magnesium isotopes in low-grade metamorphosed mudrocks

    NASA Astrophysics Data System (ADS)

    Wang, Shui-Jiong; Teng, Fang-Zhen; Rudnick, Roberta L.; Li, Shu-Guang

    2015-09-01

    Magnesium isotopic compositions of mudrocks metamorphosed at sub-greenschist facies from three lower Paleozoic basins (northern Lake District, southern Lake District, and Southern Uplands) in the British Caledonides were measured in order to understand the behavior of Mg isotopes during diagenesis and low-grade metamorphism. Carbonate-free mudrocks from the northern Lake District have heavy ?26Mg values varying from -0.17 to +0.25. By contrast, Mg isotopic compositions of carbonate-bearing mudrocks from the southern Lake District and Southern Uplands vary more widely, with ?26Mg ranging from -0.74 to -0.08. Acid leaching experiments on the latter show that the leachates have higher Ca/Al and Ca/K ratios than the residues due to the dissolution of leachable carbonates. The ?26Mg values of leachates (-1.54 to -0.21) are always lower than the corresponding residues (?26Mg = -0.39 to +0.09), consistent with isotopically light Mg in carbonates. A rough, negative correlation between ?26Mg and Mg/Al for the residual silicate fraction of mudrocks suggests that their Mg isotopic compositions are controlled by the relative proportion of illite/muscovite and chlorite. Global clastic sediments display highly variable Mg isotopic compositions that are negatively correlated with CaO/Al2O3 and CaO/TiO2, implying that carbonates introduce light Mg isotopes to sediments, although the silicate end member itself has a wide range of ?26Mg, depending on its mineralogy. Magnesium isotopic compositions of mudrocks, as well as their silicate and carbonate fractions, do not vary systemically as metamorphism proceeds from diagenesis to low-grade metamorphism, suggesting limited Mg isotope fractionation during low-temperature metamorphic dehydration (<300 C). The general decrease of Mg fraction (by mass) contributed by carbonate with increasing metamorphic grade suggests that dissolution or decomposition of carbonates during metamorphism expelled light Mg isotopes. Thus, the Mg isotopic compositions of the silicate fractions in clastic sediments more faithfully reflect their provenance signatures. Our study shows that Mg isotopes can be used to study sedimentary diagenesis, and Mg isotopes may prove a useful tracer of sediments recycled into the mantle given their heterogeneous ?26Mg values.

  11. A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation.

    PubMed

    Ho, Cheng-Ying; Mobley, Bret C; Gordish-Dressman, Heather; VandenBussche, Christopher J; Mason, Gary E; Bornhorst, Miriam; Esbenshade, Adam J; Tehrani, Mahtab; Orr, Brent A; LaFrance, Delecia R; Devaney, Joseph M; Meltzer, Beatrix W; Hofherr, Sean E; Burger, Peter C; Packer, Roger J; Rodriguez, Fausto J

    2015-10-01

    Among brain tumors, the BRAF (V600E) mutation is frequently associated with pleomorphic xanthoastrocytomas (PXAs) and gangliogliomas (GGs). This oncogenic mutation is also detected in ~5% of other pediatric low-grade gliomas (LGGs) including pilocytic astrocytomas (PAs) and diffuse astrocytomas. In the current multi-institutional study of 56 non-PXA/non-GG diencephalic pediatric LGGs, the BRAF (V600) mutation rate is 36%. V600-mutant tumors demonstrate a predilection for infants and young children (low-grade astrocytomas (LGAs) was 2212%, shorter than BRAF (V600)-WT PAs (5213%) but higher than PMAs (106%). Of note, long-term PFS was observed in several adolescent patients with BRAF (V600)-mutant tumors. In children aged 0-12years, 5-year PFS rate and median PFS in BRAF (V600)-mutant LGAs are 99% and 19months (95% CI 3-37months), respectively. The PFS is comparable to that in BRAF (V600)-WT PMAs (5-year PFS rate: 109%; median PFS: 15months, 95% CI 3-32months; p=0.96) and significantly shorter than BRAF (V600)-WT PAs (5-year PFS rate: 4613%; median PFS: 51months, 95% CI 20-? months; p<0.05). In summary, diencephalic BRAF (V600)-mutant pediatric LGAs are associated with unique clinicopathologic features and have a more aggressive clinical course, especially in children under age 13. The low rate of CDKN2A deletion also suggests that these tumors are molecularly distinct from secondary pediatric high-grade gliomas. PMID:26264609

  12. Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: case report and literature review.

    PubMed

    Oishi, Naoki; Kondo, Tetsuo; Nakazawa, Tadao; Mochizuki, Kunio; Kasai, Kazunari; Inoue, Tomohiro; Yamamoto, Takanori; Watanabe, Hiroyuki; Hatsushika, Kyousuke; Masuyama, Keisuke; Katoh, Ryohei

    2014-12-01

    Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare neoplasm characterized by morphological analogy to papillary thyroid carcinoma and abnormal expression of thyroid transcription factor-1 (TTF-1). Here we report a novel case of TL-LGNPPA with literature review. The patient was a 43-year-old woman complaining of nasal obstruction. Laryngoscopic study and computed tomography identified a pedunculated mass located on the posterior edge of the left nasal septum. Histologically, the tumor consisted of papillary growth of cuboidal or columnar epithelium. Tubular architecture and a spindle cell component were also observed focally. Some tumor cells exhibited intra-nuclear cytoplasmic inclusions. Immunohistochemically, the neoplastic cells were positive for pancytokeratin (AE1/AE3), CK7, CK19, TTF-1, vimentin and HBME1, but negative for thyroglobulin, Pax8 and CK5/6. Ki67-labeling index reached 5% in the most concentrated spot. Despite the morphological and immunohistochemical similarity to papillary thyroid carcinoma, no BRAF V600E mutation was detected by mutation-specific immunohistochemistry. The patient had neither local recurrence nor distant metastasis 19 months after removal of the tumor. PMID:24893893

  13. Clinical Management of Seizures in Patients With Low-Grade Glioma

    PubMed Central

    Piotrowski, Anna F.; Blakeley, Jaishri

    2015-01-01

    Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered. PMID:26050593

  14. Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome.

    PubMed

    Spritzer, Poli Mara; Lecke, Sheila B; Satler, Fabola; Morsch, Debora M

    2015-05-01

    Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome. PMID:25628442

  15. Low-grade, systemic inflammation in adolescents: association with early-life factors, gender, and lifestyle.

    PubMed

    Pirkola, Jatta; Vääräsmäki, Marja; Ala-Korpela, Mika; Bloigu, Aini; Canoy, Dexter; Hartikainen, Anna-Liisa; Leinonen, Maija; Miettola, Satu; Paldanius, Mika; Tammelin, Tuija H; Järvelin, Marjo-Riitta; Pouta, Anneli

    2010-01-01

    Low-grade, systemic inflammation is related to increased risk of cardiovascular disease in adults. The proinflammatory state tracks from adolescence to adulthood. Identifying correlates of inflammation in adolescents could provide opportunities to prevent cardiovascular disease in adulthood. However, population-based data on correlates of inflammation in adolescence are limited. Therefore, the authors studied the associations of early-life factors, gender, and lifestyle with inflammation (measured by high-sensitivity C-reactive protein and leukocyte count) at age 16 years (2001-2002) in the prospective, population-based Northern Finland Birth Cohort 1986 Study (n = 5,240). In females, being born small for gestational age and current use of oral contraceptives were associated with the proinflammatory state. The association of birth size with inflammation was not observed in males. In logistic regression analyses, oral contraceptive use (odds ratio (OR) = 2.83), abdominal obesity (OR = 5.17), and smoking (OR = 2.72) were associated with elevation of both inflammation markers in females; abdominal obesity (OR = 5.72) and smoking (OR = 2.02) were associated in males. Thus, females appear more susceptible to the adverse effects of being born small for gestational age than males. Given the widespread use of oral contraceptives and the potential pathophysiologic consequences of the proinflammatory state, the association of oral contraceptive use with inflammation in adolescence may have public health implications. PMID:19917553

  16. Human Papillomavirus Test for Triage of Japanese Women With Low-Grade Squamous Intraepithelial Lesions.

    PubMed

    Iwata, Takashi; Hasegawa, Toshihiko; Ochiai, Kazunori; Takizawa, Ken; Umezawa, Satoshi; Kuramoto, Hiroyuki; Ohmura, Mineo; Kubushiro, Kaneyuki; Arai, Hiroharu; Sakamoto, Masaru; Motoyama, Teiichi; Watanabe, Kayoko; Aoki, Daisuke

    2015-12-01

    We evaluated high-risk human papillomavirus (HR-HPV) DNA testing for high-grade cervical intraepithelial neoplasia (CIN) lesions by cobas HPV test and diagnostic HPV16/18 genotyping in Japanese women with low-grade squamous intraepithelial lesions. Of 357 patients, HR-HPV positivity prevalence was 75.6%, and 21.3% had grade 2 or higher CIN lesions (CIN2+), with the highest prevalence at 30 to 34 years. Negative predictive values of HR-HPV for CIN2+ in our patients were 93.1% (any age) and 94.9% (40-50 years). Absolute risk for CIN2+ in HR-HPV positive and HPV16/18 positive individuals was 25.9 and 35.1, respectively. Relative risk for CIN2+ lesions was 5.1 for HPV16/18 positive versus HR-HPV negative, and 3.8 for HR-HPV positive versus HR-HPV negative women. Predictive values of CIN2+ positive were higher for HPV16/18 positive women (any age) than 12 other HPV positive-genotypes, and highest (50%) at 40-50 years. The HPV16/18 genotyping might prevent women (>40 years) at risk of high-grade CIN lesions from undergoing unnecessary colposcopy/overtreatment of nonprogressive lesions. PMID:26092278

  17. Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment

    PubMed Central

    van Thuijl, Hinke F.; Mazor, Tali; Johnson, Brett E.; Fouse, Shaun D.; Aihara, Koki; Hong, Chibo; Malmstrm, Annika; Hallbeck, Martin; Heimans, Jan J.; Kloezeman, Jenneke J.; Stenmark-Askmalm, Marie; Lamfers, Martine L.M.; Saito, Nobuhito; Aburatani, Hiroyuki; Mukasa, Akitake; Berger, Mitchell S.; Sderkvist, Peter; Taylor, Barry S.; Molinaro, Annette M.; Wesseling, Pieter; Reijneveld, Jaap C.; Chang, Susan M.; Ylstra, Bauke; Costello, Joseph F.

    2015-01-01

    Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment nave LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ treated, hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency. PMID:25724300

  18. Optimal radiation fractionation for low-grade gliomas: Insights from a mathematical model.

    PubMed

    Galochkina, Tatiana; Bratus, Alexander; Pérez-García, Víctor M

    2015-09-01

    We study optimal radiotherapy fractionations for low-grade glioma using mathematical models. Both space-independent and space-dependent models are studied. Two different optimization criteria have been developed, the first one accounting for the global effect of the tumor mass on the disease symptoms and the second one related to the delay of the malignant transformation of the tumor. The models are studied theoretically and numerically using the method of feasible directions. We have searched for optimal distributions of the daily doses dj in the standard protocol of 30 fractions using both models and the two different optimization criteria. The optimal results found in all cases are minor deviations from the standard protocol and provide only marginal potential gains. Thus, our results support the optimality of current radiation fractionations over the standard 6 week treatment period. This is also in agreement with the observation that minor variations of the fractionation have failed to provide measurable gains in survival or progression free survival, pointing out to a certain optimality of the current approach. PMID:26113284

  19. Congenital cystic eye associated with a low-grade cerebellar lesion that spontaneously regressed

    PubMed Central

    2014-01-01

    Background Congenital cystic eye is an exceedingly rare ocular malformative disease, originated from the failure in the invagination of the optic vesicle during the fetal period and it can be associated with other ocular and non-ocular abnormalities. Diagnosis is based on clinical, radiological and histological features. Case presentation We report a case of a congenital cystic eye associated with a cerebellar lesion accidentally detected at magnetic resonance imaging. Biopsy of the mass has not been performed due to parental rejection. Based on radiologic features and absence of clinical signs, a low-grade glioma diagnosis was hypothesized, but histological characterization was not obtained. Follow-up neuro-imaging 6months after diagnosis showed that intracranial lesion spontaneously regressed without any treatment. Conclusion Our report stresses the importance of early MRI in children with ocular malformations, in order to detect associated intracranial defects, also of non-malformative origin. Additionally, we debate the clinic-radiological features of the intracranial lesions that could allow a wait-and-see policy. We also recommend a strict clinical and neuro-imaging follow-up for these lesions. Finally, biological mechanisms at the base of spontaneous regression of the brain lesions are discussed. PMID:24939368

  20. A dynamic model for the optimization of oscillatory low grade heat engines

    NASA Astrophysics Data System (ADS)

    Markides, Christos N.; Smith, Thomas C. B.

    2015-01-01

    The efficiency of a thermodynamic system is a key quantity on which its usefulness and wider application relies. This is especially true for a device that operates with marginal energy sources and close to ambient temperatures. Various definitions of efficiency are available, each of which reveals a certain performance characteristic of a device. Of these, some consider only the thermodynamic cycle undergone by the working fluid, whereas others contain additional information, including relevant internal components of the device that are not part of the thermodynamic cycle. Yet others attempt to factor out the conditions of the surroundings with which the device is interfacing thermally during operation. In this paper we present a simple approach for the modeling of complex oscillatory thermal-fluid systems capable of converting low grade heat into useful work. We apply the approach to the NIFTE, a novel low temperature difference heat utilization technology currently under development. We use the results from the model to calculate various efficiencies and comment on the usefulness of the different definitions in revealing performance characteristics. We show that the approach can be applied to make design optimization decisions, and suggest features for optimal efficiency of the NIFTE.

  1. Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas.

    PubMed

    Chen, Ricky; Ravindra, Vijay M; Cohen, Adam L; Jensen, Randy L; Salzman, Karen L; Prescot, Andrew P; Colman, Howard

    2015-03-01

    The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies. PMID:25727224

  2. Low-grade, M1 metamorphism of the western metamorphic belt near Juneau, Alaska

    SciTech Connect

    Himmelberg, G.R. . Dept. of Geology); Brew, D.A.; Ford, A.B. )

    1993-04-01

    The western metamorphic belt is part of the Coast plutonic-metamorphic complex of western Canada and southeastern Alaska that developed as a result of tectonic overlap and/or compressional thickening of crustal rocks during collision of the Alexander terrane and Gravina assemblage on the west against the Yukon Prong and Stikine terranes to the east. Sub-greenschist to lower greenschist facies metabasalts exposed along the west end of the western metamorphic belt near Juneau, Alaska record the earliest metamorphic event (M1). These low-grade rocks are gradational with younger, higher-grade assemblages that define an inverted metamorphic gradient (metamorphic event M5). The most common metamorphic mineral assemblages are chlorite-epidote-actinolite with or without pumpellyite and stilpnomelane. There is no systematic distribution of metamorphic mineral assemblages in the study area, and all assemblages are in the pumpellyite-actinolite facies near the transition to the lower greenschist facies. Different low-variance assemblages can be attributed to minor differences in pressure, temperature, or X[sub CO[sub 2

  3. Clinical Management of Seizures in Patients With Low-Grade Glioma.

    PubMed

    Piotrowski, Anna F; Blakeley, Jaishri

    2015-07-01

    Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%-2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered. PMID:26050593

  4. Optimization of reaction conditions for the electroleaching of manganese from low-grade pyrolusite

    NASA Astrophysics Data System (ADS)

    Zhang, Xing-ran; Liu, Zuo-hua; Fan, Xing; Lian, Xin; Tao, Chang-yuan

    2015-11-01

    In the present study, a response surface methodology was used to optimize the electroleaching of Mn from low-grade pyrolusite. Ferrous sulfate heptahydrate was used in this reaction as a reducing agent in sulfuric acid solutions. The effect of six process variables, including the mass ratio of ferrous sulfate heptahydrate to pyrolusite, mass ratio of sulfuric acid to pyrolusite, liquid-to-solid ratio, current density, leaching temperature, and leaching time, as well as their binary interactions, were modeled. The results revealed that the order of these factors with respect to their effects on the leaching efficiency were mass ratio of ferrous sulfate heptahydrate to pyrolusite > leaching time > mass ratio of sulfuric acid to pyrolusite > liquid-to-solid ratio > leaching temperature > current density. The optimum conditions were as follows: 1.10:1 mass ratio of ferrous sulfate heptahydrate to pyrolusite, 0.9:1 mass ratio of sulfuric acid to pyrolusite, liquid-to-solid ratio of 0.7:1, current density of 947 A/m2, leaching time of 180 min, and leaching temperature of 73°C. Under these conditions, the predicted leaching efficiency for Mn was 94.1%; the obtained experimental result was 95.7%, which confirmed the validity of the model.

  5. The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation.

    PubMed

    Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N

    2014-11-28

    Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity. PMID:25315424

  6. Enhancing low-grade thermal energy recovery in a thermally regenerative ammonia battery using elevated temperatures.

    PubMed

    Zhang, Fang; LaBarge, Nicole; Yang, Wulin; Liu, Jia; Logan, Bruce E

    2015-03-01

    A thermally regenerative ammonia battery (TRAB) is a new approach for converting low-grade thermal energy into electricity by using an ammonia electrolyte and copper electrodes. TRAB operation at 72?C produced a power density of 236 8 Wm(-2), with a linear decrease in power to 95 5 Wm(-2) at 23?C. The improved power at higher temperatures was due to reduced electrode overpotentials and more favorable thermodynamics for the anode reaction (copper oxidation). The energy density varied with temperature and discharge rates, with a maximum of 650 Wh m(-3) at a discharge energy efficiency of 54% and a temperature of 37?C. The energy efficiency calculated with chemical process simulation software indicated a Carnot-based efficiency of up to 13% and an overall thermal energy recovery of 0.5%. It should be possible to substantially improve these energy recoveries through optimization of electrolyte concentrations and by using improved ion-selective membranes and energy recovery systems such as heat exchangers. PMID:25684619

  7. Low-grade glial tumor with features of astroblastoma in a dog.

    PubMed

    Cowart, J R; Schulman, F Y; Mena, H

    2005-05-01

    A 12-year-old, neutered, male Belgian Malinois/Great Dane cross dog presented with a 5-month history of weakness and lack of endurance followed by acute onset of rear limb ataxia. At autopsy, a 9 x 16 mm, multilobular, firm, white to tan, expansile mass was found in the cerebellum. Mild dilatation of the lateral ventricles was also noted. Histologically, there was a well-demarcated glial neoplasm composed of medium-sized astrocytic elements that had homogeneous cytoplasm, sometimes with globular eosinophilic inclusions, irregular peripherally located nuclei with a single nucleolus, and short cytoplasmic processes. Prominent perivascular pseudorosettes with cellular processes in contact with blood vessels were present. Some blood vessels exhibited hyalinized walls. Mitotic figures were not observed. Immunohistochemically, neoplastic cells expressed glial fibrillary acidic protein and vimentin. These features are consistent with an astroblastoma. This is the first clinicopathologic correlation and detailed description of a low-grade glial tumor with features of astroblastoma in a dog. PMID:15872386

  8. Treatment options and neurocognitive outcome in patients with diffuse low-grade glioma.

    PubMed

    Klein, M

    2015-12-01

    In the management of patients with low-grade glioma (LGG) there still is controversy on how surgical intervention, radiotherapy, and chemotherapy contribute to an ameliorated progression-free survival, overall survival, and treatment-related neurotoxicity. With the ongoing changes in treatment options for these patients, neurocognitive functioning is an increasingly important outcome measure, because neurocognitive impairments can have a large impact on self-care, social and professional functioning, and consequently on health-related quality of life. Many factors contribute to neurocognitive outcome, such as direct and indirect tumor effects, seizures, medication, and oncological treatment. Although the role of radiotherapy has been studied extensively, the adverse effects on neurocognitive function of other treatment-related factors remain elusive. This not only holds for resective surgery, where the use of intraoperative stimulation mapping has a high potential benefit concerning survival and patient functioning, but also for the use of chemotherapy that might have some interesting new applications, like the facilitation of total resection for initially primary or recurrent diffuse LGG tumors. This paper will discuss these treatment options in LGG patients and their potential effects on neurocognitive functioning. PMID:26375636

  9. Telomerase Deficiency Causes Alveolar Stem Cell Senescence-associated Low-grade Inflammation in Lungs.

    PubMed

    Chen, Ruping; Zhang, Kexiong; Chen, Hao; Zhao, Xiaoyin; Wang, Jianqiu; Li, Li; Cong, Yusheng; Ju, Zhenyu; Xu, Dakang; Williams, Bryan R G; Jia, Jihui; Liu, Jun-Ping

    2015-12-25

    Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear. In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype. Deficiency in TERC or TERT causes a remarkable elevation in various proinflammatory cytokines, including IL-1, IL-6, CXCL15 (human IL-8 homolog), IL-10, TNF-?, and monocyte chemotactic protein 1 (chemokine ligand 2 (CCL2)); decrease in TGF-?1 and TGF?RI receptor in the lungs; and spillover of IL-6 and CXCL15 into the bronchoalveolar lavage fluids. In addition to increased gene expressions of ?-smooth muscle actin and collagen 1?1, suggesting myofibroblast differentiation, TERC deficiency also leads to marked cellular infiltrations of a mononuclear cell population positive for the leukocyte common antigen CD45, low-affinity Fc receptor CD16/CD32, and pattern recognition receptor CD11b in the lungs. Our data demonstrate for the first time that telomerase deficiency triggers alveolar stem cell replicative senescence-associated low-grade inflammation, thereby driving pulmonary premature aging, alveolar sac formation, and fibrotic lesion. PMID:26518879

  10. Clinical Epidemiology of Low-Grade and Dedifferentiated Osteosarcoma in Norway during 1975 and 2009

    PubMed Central

    Berner, Kjetil; Johannesen, Tom Brge; Bruland, yvind S.

    2015-01-01

    Purpose. To describe epidemiological, clinical characteristics and treatment outcomes of low-grade osteosarcoma (LGOS), including dedifferentiated osteosarcoma (DLGOS). Method. We analysed a nationwide cohort comprised of patients with histologically verified LGOS and DLGOS between 1975 and 2009, based on registry sources supplemented with clinical records from hospitals involved in sarcoma management. Results. Fifty-four patients were identified, 12 of whom had DLGOS. The annual incidence for all patients was 0.3 per million, with the peak incidence in the third decade of the life. Fifteen patients experienced local relapses during follow-up and ten developed metastatic diseases, including three at primary diagnosis. Patients with DLGOS dominated the metastatic relapse group. The five-year sarcoma-specific survival rate was 91%, with no documented improvement over time. Free margin following surgical resection of the primary tumour had a positive impact on survival. As expected, both local relapse and metastasis during follow-up were associated with an unfavourable outcome. Radiotherapy predicted poor survival due to the selection of high-risk patients in need of such treatment. Neither higher age nor axial tumour localisation was adverse prognostic factors. Conclusion. LGOS has an excellent prognosis when surgically resected with a free margin; however, LGOS has the potential to dedifferentiate and metastasize with a poor outcome. PMID:26412976

  11. A dynamic model for the optimization of oscillatory low grade heat engines

    SciTech Connect

    Markides, Christos N.; Smith, Thomas C. B.

    2015-01-22

    The efficiency of a thermodynamic system is a key quantity on which its usefulness and wider application relies. This is especially true for a device that operates with marginal energy sources and close to ambient temperatures. Various definitions of efficiency are available, each of which reveals a certain performance characteristic of a device. Of these, some consider only the thermodynamic cycle undergone by the working fluid, whereas others contain additional information, including relevant internal components of the device that are not part of the thermodynamic cycle. Yet others attempt to factor out the conditions of the surroundings with which the device is interfacing thermally during operation. In this paper we present a simple approach for the modeling of complex oscillatory thermal-fluid systems capable of converting low grade heat into useful work. We apply the approach to the NIFTE, a novel low temperature difference heat utilization technology currently under development. We use the results from the model to calculate various efficiencies and comment on the usefulness of the different definitions in revealing performance characteristics. We show that the approach can be applied to make design optimization decisions, and suggest features for optimal efficiency of the NIFTE.

  12. Modeling and simulation of a low-grade urinary bladder carcinoma.

    PubMed

    Bunimovich-Mendrazitsky, Svetlana; Pisarev, Vladimir; Kashdan, Eugene

    2015-03-01

    In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes affecting tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of cellular automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on the two most common types: bladder polyps and carcinoma in situ. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment. We expect our model to be a valuable tool in the study of bladder cancer progression due to the exposure to carcinogens and the oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with in vivo results reported in the corresponding medical literature. PMID:25637778

  13. The Changing Landscape of Pediatric Low-Grade Gliomas: Clinical Challenges and Emerging Therapies.

    PubMed

    Guerreiro Stucklin, Ana S; Tabori, Uri; Grotzer, Michael A

    2016-04-01

    Pediatric low-grade gliomas (PLGGs) are the most common brain tumors in children. Though histologically benign and associated with excellent outcome, patients with unresectable lesions-mostly young children with midline tumors-experience multiple progressions and are at increased risk for long-term neurological sequelae. PLGGs in children with underlying genetic predisposition syndromes-especially neurofibromatosis type 1 and tuberous sclerosis-have a distinct natural history and biology with important treatment implications. Given the complexity of medical issues, optimal management requires a large network of health care providers; treatment decisions must address both tumor control and potential side effects of the therapy. Current treatment strategies often fail to induce sustained tumor regression and many children require several lines of therapy, highlighting the need for novel therapies. Here, we review the current management of PLGG and discuss how new molecular targets-in particular alterations of the Ras/MAPK pathway-are rapidly changing our approach to PLGG. PMID:26764564

  14. Resetting of RbSr ages of volcanic rocks by low-grade burial metamorphism

    USGS Publications Warehouse

    Asmeroma, Y.; Damon, P.; Shafiqullah, M.; Dickinson, W.R.; Zartman, R.E.

    1991-01-01

    We report a nine-point RbSr whole-rock isochron age of 70??3 Ma (MSWD 3.97) for Mid-Jurassic volcanic rocks. The same rocks have also been dated by the UThPb method on zircon, giving a crystallization age of 166 ?? 11 Ma, over twice as old as the RbSr age. The data demonstrate that whole-rock RbSr ages of volcanic rocks, even lava flows with SiO2 content as low as 57 wt.%, are susceptible to complete resetting. The rocks range in composition from rhyodacite tuffs to andesite lavas. The complete breakdown of all major minerals that contain Rb and Sr resulted in an alteration mineral assemblage consisting of phengite, albite, secondary quartz, and minor amounts of chlorite and epidote. Phengite is the K-bearing product of the breakdown of biotite and K-feldspar. Pressure during low-grade metamorphism of the volcanic rocks, estimated from phengite composition to have been in the range of 4 to 6 kbar, points to thrust-related burial as the main cause of resetting. Consequently, such reset isochrons may date large-scale events such as regional thrusting and metamorphism. The coherent resetting of the RbSr isochron suggests large-scale pervasive fluid movement during thrust-related burial metamorphism. ?? 1991.

  15. Fast Thermal Calibration of Low-Grade Inertial Sensors and Inertial Measurement Units

    PubMed Central

    Niu, Xiaoji; Li, You; Zhang, Hongping; Wang, Qingjiang; Ban, Yalong

    2013-01-01

    The errors of low-cost inertial sensors, especially Micro-Electro Mechanical Systems (MEMS) ones, are highly dependent on environmental conditions such as the temperature. Thus, there is a need for the development of accurate and reliable thermal compensation models to reduce the impact of such thermal drift of the sensors. Since the conventional thermal calibration methods are typically time-consuming and costly, an efficient thermal calibration method to investigate the thermal drift of a full set of gyroscope and accelerometer errors (i.e., biases, scale factor errors and non-orthogonalities) over the entire temperature range in a few hours is proposed. The proposed method uses the idea of the Ramp method, which removes the time-consuming process of stabilizing the sensor temperature, and addresses its inherent problems with several improvements. We change the temperature linearly for a complete cycle and take a balanced strategy by making comprehensive use of the sensor measurements during both heating and cooling processes. Besides, an efficient 8-step rotate-and-static scheme is designed to further improve the calibration accuracy and efficiency. Real calibration tests showed that the proposed method is suitable for low-grade IMUs and for both lab and factory calibration due to its efficiency and sufficient accuracy. PMID:24036581

  16. Optimal management of biopsy-proven low-grade gastric dysplasia

    PubMed Central

    Kim, Jung-Wook; Jang, Jae Young

    2015-01-01

    Gastric adenocarcinoma generally culminates via the inflammation-metaplasia-dysplasia-carcinoma sequence progression. The prevalence of gastric adenomas shows marked geographic variation. Recently, the rate of diagnosis of low-grade dysplasia (LGD) has increased due to increased use of upper endoscopy. Many investigators have reported that gastric high-grade dysplasia has high potential for malignancy and should be removed; however, the treatment for gastric LGD remains controversial. Although the risk of LGD progression to invasive carcinoma has been reported to be inconsistent, progression has been observed during follow-up. Additionally, the rate of upgraded diagnosis in biopsy-proven LGD is high. Therefore, endoscopic resection (ER) may be useful in the treatment and diagnosis of LGD, especially if lesions are found to have risk factors for upgraded histology after ER, such as large size, surface erythema or depressed morphology. Fatal complications in endoscopic submucosal dissection (ESD) are extremely low and its therapeutic and diagnostic outcomes are excellent. Therefore, ESD should be applied preferentially instead of endoscopic mucosal resection. PMID:25901219

  17. Laparoscopic Right Hemicolectomy for Mucocele Due to a Low-Grade Appendiceal Mucinous Neoplasm

    PubMed Central

    Palanivelu, Chinnusamy; John, Suviraj James; Senthilkumar, Karuppusamy; Annapoorni, Shankar

    2008-01-01

    Tumors of the appendix are rare entities causing mucoceles. The majority of them are discovered incidentally during investigation for other conditions. Laparoscopic surgery for appendiceal tumors is still controversial, as inadvertent rupture of the lesion due to improper handling will cause pseudomyxoma peritonei. The patient was incidentally discovered to have an appendiceal tumor and referred to us for laparoscopy. Because the tumor involved the entire appendix, a laparoscopic right hemicolectomy was performed without directly handling the tumor. Postoperative recovery was uneventful. Pathological diagnosis was low-grade appendiceal mucinous neoplasm. The safety of laparoscopic appendectomy for the management of incidentally discovered appendiceal tumors has not yet been established. Several reports in the literature support both laparoscopic and open surgery. The main concerns to be addressed are the adequacy of resection and intraperitoneal rupture of the tumor. Our patient successfully underwent laparoscopic surgery without any complications. A formal right hemicolectomy was performed because the tumor involved the entire appendix. We now think laparoscopic surgery for appendiceal tumors is safe, feasible, and even may be beneficial. PMID:18435897

  18. Fast thermal calibration of low-grade inertial sensors and inertial measurement units.

    PubMed

    Niu, Xiaoji; Li, You; Zhang, Hongping; Wang, Qingjiang; Ban, Yalong

    2013-01-01

    The errors of low-cost inertial sensors, especially Micro-Electro Mechanical Systems (MEMS) ones, are highly dependent on environmental conditions such as the temperature. Thus, there is a need for the development of accurate and reliable thermal compensation models to reduce the impact of such thermal drift of the sensors. Since the conventional thermal calibration methods are typically time-consuming and costly, an efficient thermal calibration method to investigate the thermal drift of a full set of gyroscope and accelerometer errors (i.e., biases, scale factor errors and non-orthogonalities) over the entire temperature range in a few hours is proposed. The proposed method uses the idea of the Ramp method, which removes the time-consuming process of stabilizing the sensor temperature, and addresses its inherent problems with several improvements. We change the temperature linearly for a complete cycle and take a balanced strategy by making comprehensive use of the sensor measurements during both heating and cooling processes. Besides, an efficient 8-step rotate-and-static scheme is designed to further improve the calibration accuracy and efficiency. Real calibration tests showed that the proposed method is suitable for low-grade IMUs and for both lab and factory calibration due to its efficiency and sufficient accuracy. PMID:24036581

  19. A visfatin promoter polymorphism is associated with low-grade inflammation and type 2 diabetes.

    PubMed

    Zhang, Yuan-Yuan; Gottardo, Lucia; Thompson, Ryan; Powers, Christine; Nolan, David; Duffy, Jill; Marescotti, Maria Cristina; Avogaro, Angelo; Doria, Alessandro

    2006-12-01

    Visfatin (also known as pre-B cell colony-enhancing factor, or PBEF) is a pro-inflammatory adipokine expressed predominantly in visceral fat. We investigated whether polymorphisms at the visfatin/PBEF locus influence the risk of type 2 diabetes (T2D). Linkage disequilibrium analysis of 52 single nucleotide polymorphisms spanning the entire gene (34.7 kb) plus 20.5 kb of the upstream region and 25.5 kb of the downstream region revealed a single haplotype block that could be tagged by seven single nucleotide polymorphisms. These seven tags were typed in a group of T2D patients (n = 814) and a group of non-diabetic controls (n = 320) of white origin. A significant association was observed at -948C>A, with minor allele frequencies of 0.157 in T2D cases and 0.119 in non-diabetic controls (p = 0.021). In a non-diabetic population (n = 630), the same -948 allele that conferred increased risk of T2D was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. Our findings suggest that the visfatin/PBEF gene may play a role in determining T2D susceptibility, possibly by modulating chronic, low-grade inflammatory responses. PMID:17189536

  20. Differentiation of human innate lymphoid cells (ILCs).

    PubMed

    Juelke, Kerstin; Romagnani, Chiara

    2016-02-01

    During the last years, a high complexity in innate lymphoid lineages now collectively referred to as innate lymphoid cells (ILCs) has been revealed. ILCs can be grouped according to their effector functions and transcriptional requirements into three main groups, termed group 1, 2 and 3 ILCs. The differentiation of ILC lineages from hematopoietic precursors and the molecular switches guiding their developmental fate have started to be characterized both in mice and humans. In this review, we discuss the origin, differentiation stages and plasticity of human ILC subsets as well as the signals that drive ILC lineage commitment and acquisition of their unique effector programs. PMID:26707651

  1. Low-grade fibromyxoid sarcoma of the perineum with heterotopic ossification: case report and review of the literature.

    PubMed

    Lee, Anna F; Yip, Stephen; Smith, Adam C; Hayes, Malcolm M; Nielsen, Torsten O; O'Connell, John X

    2011-11-01

    Low-grade fibromyxoid sarcoma was first described more than 20 years ago. Subsequently, it was discovered to carry the recurrent chromosomal translocation t(7;16)(q33;p11) encoding a FUS-CREB3L2 fusion oncoprotein. Molecular tests for this pathognomonic gene fusion can confirm the identity of histologic variants (such as hyalinizing spindle cell tumor with giant rosettes) and suggest that some cases of sclerosing epithelioid fibrosarcoma may represent a high-grade version of this entity. We present a case of an ossifying tumor of the perineum that required an open biopsy and fluorescent in situ hybridization testing for FUS and CREB3L2 for diagnosis as a variant of low-grade fibromyxoid sarcoma. Subsequent excision revealed characteristic areas with collagen rosettes as well as foci of heterotopic ossification. Significant ossification, which is well documented in entities such as synovial sarcoma, ossifying fibromyxoid tumor, and extraskeletal osteosarcoma, has not been reported previously in low-grade fibromyxoid sarcoma. This case demonstrates the value of having a distinctive confirmatory molecular pathology test for diagnosis and expands our knowledge of the histologic variants possible in low-grade fibromyxoid sarcoma. PMID:21658743

  2. A preliminary study of an alternative controlled drainage strategy in surface drainage ditches: low-grade weirs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined hydrological characteristics of low-grade weirs, an alternative controlled drainage strategy in surface drainage ditches. Hydrographs of vegetated and clear scraped (control) replicates of weir vs. non-weir treatments were compared to determine differences in time to peak (Tp) a...

  3. Research on curative effect of traditional Chinese medicine treating low-grade fever of children caused by respiratory system infection.

    PubMed

    Li, Xiangyun

    2015-07-01

    This study aims to explore the curative effect of traditional Chinese medicine treating low-grade fever of children caused by respiratory system infection. Sixty children who suffered low-grade fever caused by respiratory system infection were selected and divided into treatment group and control group randomly, each with 30 cases. Control group was treated with conventional methods including oxygen uptake, nebulization and anti-infection, etc, while treatment group was given boil-free granules of traditional Chinese medicine besides the treatment which control group received. Then clinical curative effect of two groups was compared. Results showed that 28 cases (93.3%) were cured in treatment group; while 21 cases (70.0%) were cured in control group. Compared with control group, the treatment group showed up better treatment efficiency and the difference between groups was of statistical significance (P<0.05). Comparison of results of two groups suggested that, traditional Chinese medicine granules has satisfactory curative effect in the treatment of low-grade fever of children caused by respiratory system infection; characterized by short treatment cycle and effective treatment effect, Chinese medicine granules in the combination with oxygen atomization inhalation is proved to be able to efficiently remit symptoms such as coughing, gasp and labored breathing, with outstanding curative effect in the treatment of low-grade fever of children caused by respiratory system infection, thus it is worthy of popularization and application clinically. PMID:26431646

  4. Organoselenium Small Molecules and Chromium(III) Complexes for Intervention in Chronic Low-grade Inflammation and Type 2 Diabetes.

    PubMed

    Zhou, Jun; Xu, Huibi; Huang, Kaixun

    2016-01-01

    There is growing evidence to suggest that chronic, low-grade inflammation occurs in abdominal obesity, insulin resistance, type 2 diabetes mellitus and related complications, and that proinflammatory cytokines play an important role in the onset and progression of type 2 diabetes. These findings consequently provide new opportunities for the use of anti-inflammatory strategies to correct the metabolic disorders. Discovery of new synthetic bioactive small molecules to interfere with chronic, low-grade inflammation and type 2 diabetes has attracted considerable attention in medicinal chemistry. To date, a number of organoselenium small molecules and chromium(III) complexes have been shown to have the potential to alleviate chronic low-grade inflammation and type 2 diabetes, including ebselen, selenomethionine, chromium picolinate, chromium dinicocysteinate, chromium phenylalaninate, trinuclear chromium propionate, chromium histidinate, chromium nicotinate, etc. Here, we review recent advances in development of organoselenium small molecules and chromium(III) complexes to intervene in chronic low-grade inflammation and type 2 diabetes, and discuss their mode of action, potential molecular mechanisms and toxicity. PMID:26311428

  5. Role of oxidative stress and low-grade inflammation in letrozole-induced polycystic ovary syndrome in the rat.

    PubMed

    Pandey, Vivek; Singh, Anusha; Singh, Ajit; Krishna, Amitabh; Pandey, Uma; Tripathi, Yamini Bhusan

    2016-03-01

    The aims of the current study were to examine the effects of temporal changes in oxidative stress (OS) and low-grade inflammation in letrozole-treated rats and to correlate these changes with the development of polycystic ovary syndrome (PCOS)-like features. Rats were treated with letrozole for 7, 15 and 21 days to induce PCOS. On day 7 of the treatment, a significant increase in serum testosterone and high sensitive C-reactive protein (hsCRP), the low-grade inflammatory marker, was found in the letrozole treated rats compared to control rats. Moreover, a decreased immunoexpression of insulin receptor coincided with increased body weight. The strong correlation between the levels of hsCRP and lipid peroxidation (LPO) suggests simultaneous development of low-grade inflammation and OS in response to hyperandrogenism, and the role of OS in a formation of cystic follicles in the letrozole animal PCOS model. Therefore, the results of the present study suggest that OS and low-grade inflammation (hsCRP) are the major causes of PCOS induction in this model. PMID:26952756

  6. Distant dissemination of mixed low-grade astroblastoma-arteriovenous malformation after initial operation: a case report

    PubMed Central

    Yao, Kun; Wu, Bin; Xi, Mei; Duan, Zejun; Wang, Jiqiang; Qi, Xueling

    2015-01-01

    We present a rare case of low-grade astroblastoma coexisting with an arteriovenous malformation (AVM) underwent surgery two times in a 38-year-old man. After the first surgery, this case was reported as a mixed low-grade astroblastoma and AVM. The lesion was completely resected surgically along with AVM. The patient underwent postoperative radiotherapy. Twenty months later, MRI showed enhanced lesions in suprasellar, pineal region and multiple small lesions in the spinal cord, whereas completely no recurrent lesion at the primary tumor site. So, the patient rationally underwent surgical removal in suprasellar and pineal region. After the second surgery, this case was diagnosed as a high-grade astroblastoma. Cells from the second surgical specimens showed high MIB-1 index and an increased olig-2 index. In addition, it is not common for low-grade astroblastoma metastasis to suprasellar, pineal region and spine with completely no recurrence at the original primary tumor site. Therefore it is difficult to predict tumor behavior and patient’s clinical outcome merely based on histologic features. The important issue is whether the AVM was thought to be the cause of poor progress of this tumor. More cases are needed to confirm this. Classification and histogenesis of this tumor is still debated. Lack of clinicopathological correlation makes the prognosis of this tumor unpredictable. Anyway, we should be very discreet to treat the astroblastoma, even for low-grade astroblastoma. PMID:26261652

  7. Diffuse lymphoid follicles of the colon associated with colonic carcinoma.

    PubMed

    Bronen, R A; Glick, S N; Teplick, S K

    1984-01-01

    In four patients aged 59-75 years, colonic carcinoma was associated with diffuse lymphoid follicles in the colon. In one case, the prominence and distribution of the lymphoid follicles corresponded to the progression and regression of the tumor bulk. It is extremely unusual to demonstrate lymphoid follicles, particularly diffuse, on barium enema in patients in this age range. The colonic carcinomas and lymphoid follicles are directly related, possibly representing an immune response. PMID:6606941

  8. Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma.

    PubMed

    Dewaele, Barbara; Przybyl, Joanna; Quattrone, Anna; Finalet Ferreiro, Julio; Vanspauwen, Vanessa; Geerdens, Ellen; Gianfelici, Valentina; Kalender, Zeynep; Wozniak, Agnieszka; Moerman, Philippe; Sciot, Raf; Croce, Sabrina; Amant, Frederic; Vandenberghe, Peter; Cools, Jan; Debiec-Rychter, Maria

    2014-03-01

    Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are commonly driven by recurrent gene rearrangements. In conventional low-grade ESS, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1, and recently described ZC3H7-BCOR chimeric fusions have been reported in > 50% of cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and banding cytogenetics, we identified MBTD1 (malignant brain tumor domain-containing 1) and CXorf67 (chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using reverse-transcription polymerase chain reaction followed by Sanger sequencing. A specific FISH assay was developed to detect the novel t(X;17) translocation in formalin-fixed paraffin-embedded material, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 25 uterine stromal tumors [14 ESS and 11 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of seven ESS (including three with YWHAE and two with JAZF1 rearrangements) and four UES without specific chromosomal aberrations indicated clustering of tumors with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESS. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. PMID:23959973

  9. Intranasal immunization with polymer-grafted microparticles activates the nasal-associated lymphoid tissue and draining lymph nodes.

    PubMed Central

    Heritage, P L; Brook, M A; Underdown, B J; McDermott, M R

    1998-01-01

    Waldeyer's ring is located at the juncture of the respiratory and alimentary tracts, where it is bombarded by inhaled and ingested antigens. However, knowledge of its exact function or consequences of its removal is incomplete. Recently, the murine nasal-associated lymphoid tissue (NALT) has been reported to have functional similarities to Waldeyer's ring and, thus, might be a suitable model to examine the function of oronasopharyngeal lymphoid tissues. To explore the capability of NALT to incite local mucosal and systemic immunity, we immunized mice intranasally (i.n.) with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS)-grafted microparticles (MP), an inoculant previously shown to induce robust systemic and mucosal humoral immunity following intragastric (i.g.) administration. We demonstrated that i.n. immunization with low doses of microentrapped, but not soluble, human serum albumin (HSA) evoked robust circulating IgG responses (P < 0.05). Additionally, NALT cells isolated from MP-treated mice proliferated in vitro when restimulated with HSA (P < 0.05), suggesting that i.n. immunization with HSA-containing MP incited specific immunity via NALT cell activation. Coinciding with these observations, after i.n. MP administration HSA-specific spot-forming cells (SFC) were observed in NALT, and later posterior cervical lymph nodes (pCLN) and spleen (SPL), suggesting that the observed MP-induced specific systemic antibody responses emanated from the NALT. We also showed that i.n. immunization with HSA-containing TS-PDMS-grafted MP stimulated interleukin-4 (IL-4)-secreting lymphocytes in the NALT. This cytokine microenvironment was probably responsible for driving the IgG1 sera response observed after i.n. MP administration, via the migration of NALT-derived IgG1-committed B cells. Interestingly, unlike i.g. MP administration, i.n. immunization with HSA-containing MP did not evoke detectable specific IgA in any lymphoid tissue examined, or in nasal secretions, probably reflecting differences between NALT and other mucosae-associated lymphoid tissues (MALT). PMID:9616375

  10. Use of fludarabine in the treatment of mantle cell lymphoma, Waldenstrm's macroglobulinemia and other uncommon B- and T-cell lymphoid malignancies.

    PubMed

    Johnson, Stephen A

    2004-01-01

    After initial efforts using fludarabine as a single agent in the treatment of acute leukemia, its activity at lower and safer doses was demonstrated in chronic lymphocytic leukemia (CLL) patients who were refractory or had relapsed from traditional chemotherapies, representing a highly effective therapy for this condition. Fludarabine was also rapidly shown to be beneficial as first-line therapy in CLL. There is now considerable evidence that fludarabine is an effective agent in non-Hodgkin's lymphoma and in combination therapy for acute myeloid leukemia. Further, good responses are achieved when fludarabine-based approaches are used as conditioning regimens prior to transplantation procedures. The actions of fludarabine are not restricted to these settings and its potential role in the treatment of a range of uncommon T- and B-cell lymphoid malignancies is slowly emerging. This review will focus on the characteristics and treatment options for two B-cell disorders, mantle cell lymphoma and Waldenstrm's macroglobulinemia, with emphasis on the clinical activity of fludarabine. Additionally, the advantages of using fludarabine-containing regimens for a range of other lymphoproliferative conditions will also be discussed. These include B-cell neoplasms such as the CLL variant prolymphocytic leukemia, hairy cell leukemia and mucosa-associated lymphoid tissue-derived lymphomas; the T-cell disorders cutaneous T-cell lymphoma, angioimmunoblastic lymphadenopathy and other rarer T-cell diseases; and aggressive variants of non-Hodgkin's lymphoma including Richter's syndrome. PMID:15079153

  11. The Immune Protective Effect of the Mediterranean Diet against Chronic Low-grade Inflammatory Diseases

    PubMed Central

    Casas, Rosa; Sacanella, Emilio; Estruch, Ramon

    2014-01-01

    Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fiber from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of proinflammatory cytokines associated with a reduced production of anti-inflammatory cytokines. The Mediterranean Diet (MedDiet) is a nutritional model inspired by the traditional dietary pattern of some of the countries of the Mediterranean basin. This dietary pattern is characterized by the abundant consumption of olive oil, high consumption of plant foods (fruits, vegetables, pulses, cereals, nuts and seeds); frequent and moderate intake of wine (mainly with meals); moderate consumption of fish, seafood, yogurt, cheese, poultry and eggs; and low consumption of red meat, processed meat products and seeds. Several epidemiological studies have evaluated the effects of a Mediterranean pattern as protective against several diseases associated with chronic low-grade inflammation such as cancer, diabetes, obesity, atherosclerosis, metabolic syndrome and cognition disorders. The adoption of this dietary pattern could counter the effects of several inflammatory markers, decreasing, for example, the secretion of circulating and cellular biomarkers involved in the atherosclerotic process. Thus, the aim of this review was to consider the current evidence about the effectiveness of the MedDiet in these chronic inflammatory diseases due to its antioxidant and anti-inflammatory properties, which may not only act on classical risk factors but also on inflammatory biomarkers such as adhesion molecules, cytokines or molecules related to the stability of atheromatic plaque. PMID:25244229

  12. Evolving management of low grade glioma: No consensus amongst treating clinicians.

    PubMed

    Field, K M; Rosenthal, M A; Khasraw, M; Sawkins, K; Nowak, A K

    2016-01-01

    Following the widely publicized presentation of the Radiation Therapy Oncology Group (RTOG) 9802 data, we sought to understand how these data had been translated to the management of low grade gliomas (LGG) by Australian neuro-oncology clinicians. The de novo management of LGG is transitioning to include postoperative radiotherapy and chemotherapy after the RTOG 9802 study results demonstrated a survival benefit in this setting. In 2014, neurosurgeons, radiation oncologists and neuro-oncologists who were members of the Australian Cooperative Trials Group for Neuro-oncology (COGNO), as well as additional attendants of the COGNO annual scientific meeting, were surveyed. The survey presented six LGG clinical scenarios and asked respondents to select their preferred management strategy. Some additional questions included the respondents' approach to 1p/19q testing and chemotherapy preferences. The response rate was 30.2% (61/202), with the majority (77%) working in tertiary referral neuro-oncology centers. There was no consensus regarding the management approach for each scenario, with postsurgery observation alone remaining a popular strategy. Only 25% of respondents reported that their institution routinely tests for 1p/19q status in LGG, although 69% were of the opinion that all LGG patients should be tested. The majority (81%) preferred to use temozolomide rather than the procarbazine, lomustine, and vincristine combination as the first line chemotherapy for LGG, but only 44% would actually use it in this setting. Up front chemotherapy, prior to radiotherapy, would be considered by 52% of respondents for certain LGG patients. This survey assessed the management strategies for LGG since the updated RTOG 9802 data were presented. It demonstrates no consensus in the postoperative treatment approaches for LGG. PMID:26601811

  13. An extraction process to recover vanadium from low-grade vanadium-bearing titanomagnetite.

    PubMed

    Chen, Desheng; Zhao, Hongxin; Hu, Guoping; Qi, Tao; Yu, Hongdong; Zhang, Guozhi; Wang, Lina; Wang, Weijing

    2015-08-30

    An extraction process to recover vanadium from low-grade vanadium-bearing titanomagnetite was developed. In this study, a mixed solvent system of di(2-ethylhexyl) phosphate (D2EHPA) and tri-n-butyl phosphate (TBP) diluted with kerosene was used for the selective extraction of vanadium from a hydrochloric acid leaching solution that contained low vanadium concentration with high concentrations of iron and impurities of Ca, Mg, and Al. In the extraction process, the initial solution pH and the phase ratio had considerable functions in the extraction of vanadium from the hydrochloric acid leaching solution. Under optimal extraction conditions (i.e., 30-40°C for 10min, 1:3 phase ratio (O/A), 20% D2EHPA concentration (v/v), and 0-0.8 initial solution pH), 99.4% vanadium and only 4.2% iron were extracted by the three-stage counter-current extraction process. In the stripping process with H2SO4 as the stripping agent and under optimal stripping conditions (i.e., 20% H2SO4 concentration, 5:1 phase ratio (O/A), 20min stripping time, and 40°C stripping temperature), 99.6% vanadium and only 5.4% iron were stripped by the three-stage counter-current stripping process. The stripping solution contained 40.16g/LV2O5,0.691g/L Fe, 0.007g/L TiO2, 0.006g/L SiO2 and 0.247g/L CaO. A V2O5 product with a purity of 99.12% V2O5 and only 0.026% Fe was obtained after the oxidation, precipitation, and calcination processes. The total vanadium recovered from the hydrochloric acid leaching solution was 85.5%. PMID:25840036

  14. Learning and Memory Following Conformal Radiation Therapy for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Di Pinto, Marcos; Conklin, Heather M.; Li, Chenghong; Merchant, Thomas E.

    2012-11-01

    Purpose: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning. Methods and Materials: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years. Results: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy. Conclusions: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.

  15. Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2*

    PubMed Central

    Ruszkowska-Ciastek, Barbara; Sokup, Alina; Wernik, Tomasz; Rhone, Piotr; Góralczyk, Krzysztof; Bielawski, Kornel; Fijałkowska, Agata; Nowakowska, Aleksandra; Rhone, Elżbieta; Rość, Danuta

    2015-01-01

    Objective: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. Methods: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. Results: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. Conclusions: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca2+. The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications. PMID:26365121

  16. Cellular metabolic regulators: Novel indicators of low-grade inflammation in humans

    PubMed Central

    Haimovich, Beatrice; Zhang, Zhiyong; Calvano, Jacqueline E; Calvano, Steve E; Kumar, Ashwini; Macor, Marie A; Corbett, Siobhan; Coyle, Susette M; Lowry, Stephen F.

    2015-01-01

    Introduction The Toll like receptor 4 (TLR4) ligand endotoxin triggers robust systemic inflammatory responses in humans at doses > 1.0 ng/kg. In this study we tested the hypothesis that evidence of TLR4-induced responses would be detectable in leukocytes challenged with endotoxin doses that are below the threshold needed to trigger a characteristic systemic inflammatory phenotype in humans. Methods Subjects were challenged with endotoxin at 1, 0.5, or 0.1 ng/kg (n=5 per dose). Systemic responses were monitored for 24 hour. Blood samples, collected at designated interval for up to 24 hours post-challenge, were used to determine plasma cytokines levels, total and differential leukocyte counts, expression of leukocyte cell surface receptors, and changes in the leukocyte transcriptome. Western blotting was used to determine changes in leukocyte protein expression. Results We found that in vivo endotoxin at concentrations <1.0 ng/kg triggers weak and variable responses in humans. In marked contrast, we show that endotoxin at a concentration as low as 0.1 ng/kg triggers a transient decline in cellular ATP levels in leukocytes. This is associated with the appearance of a unique protein expression signature in leukocytes. The protein expression signature includes three prominent features: i) AMP-activated protein kinase subunit ? (AMPK?) degradation, ii) increased HIF-1? expression, and iii) autophagy, collectively indicative of a regulated metabolic response. An indistinguishable response phenotype was observed in human leukocytes treated with endotoxin in vitro. Discussion These data demonstrate for the first time in humans that a TLR4 ligand concentration that is below the threshold needed to trigger clinically evident systemic inflammatory manifestations initiates a transient decline in ATP levels, AMPK? degradation, HIF-1? expression, and autophagy in leukocytes. This establishes that low-grade TLR4 activation exerts control over leukocyte metabolism in the absence of systemic inflammatory indicators. PMID:23817504

  17. Longitudinal Investigation of Adaptive Functioning Following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-04-01

    Purpose: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. Results: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

  18. Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Iseki, Hiroshi; Ikuta, Soko; Konishi, Yoshiyuki; Saito, Taichi; Tamura, Manabu; Chernov, Michael; Watanabe, Atsushi; Okamoto, Saori; Maebayashi, Katsuya; Mitsuhashi, Norio; Okada, Yoshikazu

    2013-01-01

    The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ?90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ?90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy. PMID:23883555

  19. Solidification/stabilisation of electric arc furnace waste using low grade MgO.

    PubMed

    Cubukcuoglu, B; Ouki, S K

    2012-02-01

    This study aims to evaluate the potential of low grade MgO (LGMgO) for the stabilisation/solidification (S/S) of heavy metals in steel electric arc furnace wastes. Relevant characteristics such as setting time, unconfined compressive strength (UCS) and leaching behaviour assessed by acid neutralisation capacity (ANC), monolithic and granular leaching tests were examined in light of the UK landfill Waste Acceptance Criteria (WAC) for disposal. The results demonstrated that all studied mix designs with Portland cement type 1 (CEM1) and LGMgO, CEM1-LGMgO 1:2 and 1:4 at 40% and 70% waste addition met the WAC requirements by means of UCS, initial and final setting times and consistence. Most of the ANC results met the WAC limits where the threshold pH values without acid additions were stable and between 11.9 and 12.2 at 28d. Granular leaching results indicate fixation of most of the metals at all mix ratios. An optimum ratio was obtained at CEM1-LGMgO 1:4 at 40% waste additions where none of the metals leaching exceeded the WAC limits and hence may be considered for landfill disposal. The monolithic leaching test results showed that LGMgO performed satisfactorily with respect to S/S of Zn, as the metal component present at the highest concentration level in the waste exhibited very little leaching and passed the leaching test requirement at all mix ratios studied. However, its performance with respect to Pb, Cd and Cr was less effective in reducing their leaching suggesting a higher cumulative rate under those leaching regimes. PMID:22172635

  20. Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition.

    PubMed

    Meng, F R; Bourque, C P; Belczewski, R F; Whitney, N J; Arp, P A

    1995-01-01

    Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane. Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning. It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates. Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age. Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones. Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition. Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age. Many fungal taxa were isolated and identified. It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition. Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces. Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same. In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition. PMID:15091479

  1. Seizure reduction is a prognostic marker in low-grade glioma patients treated with temozolomide.

    PubMed

    Koekkoek, Johan A F; Dirven, Linda; Heimans, Jan J; Postma, Tjeerd J; Vos, Maaike J; Reijneveld, Jaap C; Taphoorn, Martin J B

    2016-01-01

    We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a?50% seizure reduction and MRI response 6, 12 and 18months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95% CI 0.19-0.73; p=0.004) and OS (HR 0.39; 95% CI 0.18-0.85; p=0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95% CI 62.0-112.9) than patients without a response (median 34.4mo; 95% CI 26.1-42.6; p=0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response. PMID:26547911

  2. Modulating apoptosis pathways in low-grade B-cell malignancies using biological response modifiers.

    PubMed

    Reed, John C; Kitada, Shinichi; Kim, Youngsoo; Byrd, John

    2002-02-01

    Collectively, low-grade B-cell malignancies constitute the fifth most common form of potentially lethal cancer in North America and Europe, with chronic lymphocytic leukemia (CLL) and follicular non-Hodgkin's lymphoma (FL) representing the most prevalent of these disorders. Chronic lymphocytic leukemia and FL represent quintessential examples of human malignancies that are caused primarily by defects in programmed cell death (apoptosis). During the early stages of disease, the mature B lymphocytes that comprise most CLLs and FLs are largely quiescent G(0) phase cells, which accumulate not because they are dividing more rapidly than normal but because they survive longer than their normal counterparts because of defects in the normal pathways for apoptosis. Defects in apoptosis pathways contribute to chemoresistance, rendering tumor cells less sensitive to the cytotoxic actions of currently available anticancer drugs, and can also promote resistance to cellular immune responses. Several biological agents or their synthetic derivatives show promise as apoptosis modulators, having the potential to place neoplastic cells into a more susceptible state or activating latent programs for cell suicide. These biological response modifiers include monoclonal antibodies such as rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) that alter signal transduction pathways, cytokines such as TRAIL (Apo2 ligand), ligands for retinoid/steroid family nuclear receptors, and small-molecule compounds that bind and inhibit protein kinases. Knowledge about the mechanisms by which these agents influence apoptosis pathways in neoplastic diseases may suggest strategies for more effective and less toxic therapies for patients suffering from CLL, FL, and other malignancies. PMID:11842384

  3. A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Menjot de Champfleur, Nicolas; Costi, Emanuele; Bonnetblanc, Franois; Duffau, Hugues

    2015-04-01

    Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia. PMID:25687031

  4. Evidence for low-grade metamorphism, hydrothermal alteration, and diagenesis on mars from phyllosilicate mineral assemblages

    USGS Publications Warehouse

    Ehlmann, B.L.; Mustard, J.F.; Clark, R.N.; Swayze, G.A.; Murchie, S.L.

    2011-01-01

    The enhanced spatial and spectral resolution provided by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on the Mars Reconnaissance Orbiter (MRO) has led to the discovery of numerous hydrated silicate minerals on Mars, particularly in the ancient, cratered crust comprising the southern highlands. Phases recently identified using visible/near-infrared spectra include: smectite, chlorite, prehnite, high-charge phyllosilicates (illite or muscovite), the zeolite analcime, opaline silica, and serpentine. Some mineral assemblages represent the products of aqueous alteration at elevated temperatures. Geologic occurrences of these mineral assemblages are described using examples from west of the Isidis basin near the Nili Fossae and with reference to differences in implied temperature, fluid composition, and starting materials during alteration. The alteration minerals are not distributed homogeneously. Rather, certain craters host distinctive alteration assemblages: (1) prehnite-chlorite-silica, (2) analcime-silica-Fe,Mg-smectite-chlorite, (3) chlorite-illite (muscovite), and (4) serpentine, which furthermore has been found in bedrock units. These assemblages contrast with the prevalence of solely Fe,Mg-smectites in most phyllosilicate-bearing terrains on Mars, and they represent materials altered at depth then exposed by cratering. Of the minerals found to date, prehnite provides the clearest evidence for subsurface, hydrothermal/metamorphic alteration, as it forms only under highly restricted conditions (T = 200 400??C). Multiple mechanisms exist for forming the other individual minerals; however, the most likely formation mechanisms for the characteristic mineralogic assemblages observed are, for (1) and (2), low- grade metamorphism or hydrothermal (400??C has not been found.

  5. IDH mutation is associated with higher risk of malignant transformation in low-grade glioma.

    PubMed

    Leu, Severina; von Felten, Stefanie; Frank, Stephan; Boulay, Jean-Louis; Mariani, Luigi

    2016-04-01

    Acquisition of IDH1 or IDH2 mutation (IDHmut) is among the earliest genetic events that take place in the development of most low-grade glioma (LGG). IDHmut has been associated with longer overall patient survival. However, its impact on malignant transformation (MT) remains to be defined. A collection of 210 archived adult LGG previously stratified by IDHmut, MGMT methylation (MGMTmet), 1p/19q combined loss of heterozygosity (1p19qloh) and TP53 immunopositivity (TP53pos) status was analyzed. We used multistate models to assess MT-free survival, considering one initial, one transient (MT), and one absorbing state (death). Missing explanatory variables were multiply imputed. Overall, although associated with a lower risk of death (HRDEATH=0.35, P=0.0023), IDHmut had a non-significantly higher risk of MT (HRMT=1.84; P=0.1683) compared to IDH wild type (IDHwt). The double combination of IDHmut and MGMTmet and the triple combination of IDHmut, MGMTmet and 1p/19qloh, despite significantly lower hazards for death (HRDEATH versus IDHwt: 0.35, P=0.0194 and 0.15, P=0.0008, respectively), had non-significantly different hazards for MT. Conversely, the triple combination of IDHmut/MGMTmet/TP53pos, with a non-significantly different hazard for death, had a significantly higher hazard for MT than IDHwt (HRMT versus IDHwt: 2.83; P=0.0452). Although IDHmut status is associated with longer overall patient survival, all IDHmut/MGMTmet subsets consistently showed higher risks of MT than of death, compared to IDHwt LGG. This supports the findings that molecular events relevant to IDH mutations impact early glioma development prior to malignant transformation. PMID:26780338

  6. Low-grade cribriform cystadenocarcinoma of the palatal gland: A case report

    PubMed Central

    KOKABU, SHOICHIRO; NOJIMA, JUNYA; KAYANO, HIDEKAZU; YODA, TESTUYA

    2015-01-01

    Low-grade cribriform cystadenocarcinoma (LGCCC) is a malignant salivary gland tumor. LGCCC occurs rarely, with the parotid gland being the most commonly afflicted site. Few cases arise in other sites. The present study reports a case of LGCCC that occurred at the palatal gland of the hard palate. A 56-year-old female was referred to Saitama Medical University Hospital (Moroyama, Saitama, Japan) due to an intraoral mass. Since cytological examination and biopsy led to a diagnosis favoring a neoplasm, but with uncertain malignant potential, the tumor was resected with a safe surgical margin. The specimen was thoroughly examined. Microscopically, there was a well-demarcated, unilocular cyst with the lumen lined by tumor cells. The tumor cells were arranged in tubular, cribriform and solid structures in the area of the intracystic mass lesions. Nuclear atypia was inconspicuous, although mitotic figures were observed throughout the tumor. Neither local nor perineural invasion was present. On immunohistochemistry, the tumor cells were diffusely positive for S-100 protein. Myoepithelial markers, calponin and p63, highlighted the cells rimming the cystic mass. The final histopathological diagnosis was of LGCCC. The tumor was completely resected. At 1 year post-resection, the patient exhibited no recurrence or distant metastasis. LGCCC is regarded as clinically indolent. However, there is little literature available to aid with prognosis prediction due to the rarity of LGCCC cases. Thus, greater experience and longer follow-up periods are necessary to find the optimal/curative treatment for patients with LGCCC and to clarify the pathophysiology. PMID:26622870

  7. Mediterranean diet and low-grade subclinical inflammation: the Moli-sani study.

    PubMed

    Bonaccio, Marialaura; Cerletti, Chiara; Iacoviello, Licia; de Gaetano, Giovanni

    2015-01-01

    Low-grade chronic inflammation is an underlying pathophysiological mechanism linking risk factors and/or metabolic disorders to increased risk of chronic degenerative disease. A meat-based pattern, as the Western type diet, is positively linked to higher levels of some important biomarkers of inflammation, such as C-reactive protein (CRP), interleukin-6 and fibrinogen. Conversely, a Mediterranean-like eating behavior is associated with lower degree of these biomarkers thus suggesting an anti-inflammatory action of its main food components. This chapter goes through the most important investigations addressing the relationship between dietary habits and subclinical inflammation. Attention was focussed on the findings from the Moli-sani study: this is a large prospective cohort study that recruited 24,325 men and women from the general population of the Molise Region, a Southern Italian area, with the aim of investigating genetic and environmental risk/protection factors for cardiovascular and tumor disease. For the first time, the Moli-sani study carefully investigated the Mediterranean diet as an environmental determinant of both platelet and white blood cell counts, starting from the hypothesis that a diet rich in healthy compounds could favorably influence the production and/or the clearance of these two cellular biomarkers of lowgrade inflammation. Additionally, evidence from this large Italian cohort showed that a Mediterranean-like diet was closely associated with relatively lower values of glucose, lipids, CRP, blood pressure and 10-year cardiovascular risk, while the consumption of healthy foods with high rather than low content in antioxidant vitamins and phytochemicals was associated with lower blood pressure and CRP plasma levels at least in men. PMID:25329200

  8. Proton Therapy in Pediatric Skull Base and Cervical Canal Low-Grade Bone Malignancies

    SciTech Connect

    Habrand, Jean-Louis Schneider, Ralf M.D.; Alapetite, Claire; Feuvret, Loic; Petras, Slavo; Datchary, Jean; Grill, Jacques; Noel, Georges; Helfre, Sylvie; Ferrand, Regis; Bolle, Stephanie; Sainte-Rose, Christian

    2008-07-01

    Purpose: To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. Patients and Methods: Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. Results: With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). Conclusions: High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.

  9. Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

    PubMed

    Goodarzi, Mahmoud; Correa, Arlene M; Ajani, Jaffer A; Swisher, Stephen G; Hofstetter, Wayne L; Guha, Sushovan; Deavers, Michael T; Rashid, Asif; Maru, Dipen M

    2009-12-01

    The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n=19), indefinite for dysplasia (n=11), low-grade dysplasia (n=27), high-grade dysplasia (n=19), or adenocarcinoma (n=12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylin-eosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann-Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (P<0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (P<0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P<0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus-low-grade dysplasia-high-grade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples. PMID:19734842

  10. Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

    ClinicalTrials.gov

    2015-12-14

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Value added products with popular low grade rice varieties of Andhra Pradesh.

    PubMed

    Anitha, G; Rajyalakshmi, P

    2014-12-01

    Eight Popular Low Grade Rice Varieties (PLRVs) MTU 3626, MTU 1001, MTU 1010, MTU 4870 and NLR 145, NLR 34242, NLR 30491, NLR 34449, (developed and released by ANGR agricultural University, Andhra Pradesh) having poor cooking quality were selected for the study. ANGRAU variety BPT 5204 popularly consumed as staple rice was used as check. Eight products of traditional/commercial importance were standardized incorporating PLRVs as a major ingredient in the form of rice flour (burfi, noodles and extruded snack product and vennaundalu (butter coated balls), palathalikalu (dough rolled into strips, steamed/cooked in milk); rice semolina (instant kheer mix and instant upma mix), and flaked rice (nutritious bar). The products were evaluated for nutritional, cooking quality characteristics, consumer acceptability and shelf-life. Consumer acceptability of the PLR products was carried out with 60 farm women based on 9 point hedonic scale. Shelf-life of the products (packed in both metalized PP and PE pouches) was evaluated monthly for chemical, microbiological and sensory parameters. Energy values of control and PLR products showed no significant difference. Upon cooking, PLR Noodles showed no significant difference with water absorption and volume but more (p?

  12. Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Ikuta, Soko; Komori, Takashi; Maebayashi, Katsuya; Iseki, Hiroshi; Tamura, Manabu; Saito, Taiichi; Okamoto, Saori; Chernov, Mikhail; Hayashi, Motohiro; Okada, Yoshikazu

    2015-01-01

    OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ? 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection. PMID:25599276

  13. AT-42FACTORS ASSOCIATED WITH MALIGNANT TRANSFORMATION OF LOW-GRADE GLIOMA

    PubMed Central

    Moriya, Keisuke; Nitta, Masayuki; Maruyama, Takashi; Saito, Taichi; Ikuta, Shoko; Okada, Yoshikazu; Iseki, Hiroshi; Muragaki, Yoshihiro

    2014-01-01

    BACKGROUND: There is no standard therapeutic regimen for low-grade glioma (LGG). We have suggested extent of resection (EOR) was strongly associated with prognosis of LGG. About half of LGG eventually show malignant transformation (MT), MT is an important factor in determining prognosis of LGG. Therefore, it is important to definite factors associated with MT. In this study, we investigated correlation between MT and genetic profile and adjuvant therapy in LGG. METHOD: 151 patients (Male: Female = 80:71) with LGG treated in our institute from 2000 to 2010 were retrospectively analyzed. Median follow-up period was 41months, follow-up ratio was 96, and the average age was 39.1 year-old (15-65). Diffuse astrocytoma (DA) accounted 47 patients (31), oligodendroglioma (O) was 55 patients (37), oligoastrocytoma (OA) was 44 patients (29). The median Mib-1 index was 4.8. IDH1 mutation and co-deletion of 1p19q locus were analyzed by immunohistochemistry and FISH method, respectively. RESULT: The average and median EOR of T2 high area was 85 and 95, respectively. ACNU based chemotherapy was performed in 35 patients and radiotherapy in 48 patients. IDH1 mutation and 1p19q co-deletion were 75 and 57%, respectively. 48 patients out of 151 recurred and 29 patients were MT. Patients without IDH1 mutation (P = 0.025) or 1p19q deletion (P = 0.001) showed significant higher rate of MT. In analysis of all patients, EOR strongly correlated with MT (P = 0.0002). EOR correlated with MT in DA (P = 0.0003) but not in oligodendroglial subtypes (P = 0.7). In IDH1 mutant group, chemotherapy reduced MT (P = 0.004), however, in IDH1 wild-type group, both radiotherapy (P = 0.004) and chemotherapy (P = 0.006) brought higher incidence of MT. CONCLUSION: EOR significantly prevented MT in DA. It was suggested that IDH1 was a predictive factor for MT following radiotherapy and chemotherapy in LGG. Extensive resection is required for IDH1 wild type DA.

  14. Chemical mobility during low-grade metamorphism of a Jurassic lava flow: Ro Grande Formation, Peru

    NASA Astrophysics Data System (ADS)

    Aguirre, L.

    Chemical and mineralogical changes produced by very low-grade metamorphism in a 40 meter thick, K-rich, calc-alkaline andesite flow of the marine Jurassic Ro Grande Formation of southern coastal Peru are discussed. This metamorphism (=spilitization) was non-deformational and generated spilitic domains at (and near) both vesicular margins of the flow, whereas the massive central zone remained relatively unaltered. The metadomains are characterized by mineral associations of the zeolite facies. Primary minerals are Ca-plagioclase, augitic pyroxene, iron-titanium oxides, and (pseudomorphs after) olivine. Metamorphic minerals are: albite (three generations), K-feldspar, pumpellyite, chlorite, interlayered chlorite-celadonite, celadonite, various mixed-layer Si- and Fe-rich phyllosilicates, "iddingsite," calcite, analcime, titanite, and white mica. The effect of the metamorphism on the rock chemistry is reflected in changes especially observed at the marginal zones of the flow which affect major, trace, and RE elements: 1) strong increase of the iron oxidation ratio (Fe 2O 3/FeO); 2) enrichment in Na 2O accompanied by a concomitant depletion of CaO in non-amygdaloidal domains; 3) depletion of SiO 2; 4) strong enrichment in H 2O and CO 2; 5) marked depletion of Sr and Rb; 6) enrichment in Cl and S; and 7) slight depletion in RE elements, notably in the top zone of the flow. Conversely, elements such as Ti, P, Nb, and Y were fairly immobile, whereas Zr and K were only slightly mobilized. The effect of the metamorphism on the mineral chemistry is expressed by the predominance of metastable equilibrium evidenced by the existence of wide compositional ranges in the phyllosilicates, the incomplete albitization of the Ca-plagioclase, and the Al-rich character of the pumpellyites. The metamorphism is considered to be of hydrothermal-burial type, which takes place at low temperature and pressure probably about 125-230C and less than 3 kb, and is produced mainly through permeability-controlled seawater/rock interaction.

  15. Dehydration Behavior of Metapelites and Metabasites at Very low to low Grade Metamorphic Conditions

    NASA Astrophysics Data System (ADS)

    Massonne, H.; Willner, A. P.

    2007-12-01

    Thermodynamic calculations have been undertaken in the system Na-Ca-K-Fe-Mg-Al-Si-Ti-H-O with the PERPLE_X software package (Connolly, 1990 and updates) for a better understanding of the dehydration behavior of metapelites and metabasites during prograde metamorphism. To obtain reasonable results for the temperature range 150-450 C at pressures up to 25 kbar, the subsequent solid solution models were introduced being compatible with the applied thermodynamic data set of Holland & Powell (1998 and updates): a three component model for Mg-Fe2+-Fe3+-pumpellyite, a two component model for Fe2+-Mg- stilpnomelane, a four component amphibole model (tremolite - Fe2+-tremolite - glaucophane - Mg- riebeckite), and a four component Na-pyroxene model (acmite - jadeite - diopside - hedenbergite). The water contents released by prograde metamorphism up to 450 C from MORB and psammopelitic compositions on top of oceanic crust, were obtained by calculating P-T pseudosections. Metabasite contains 6-7 wt% H2O bound to minerals at 150 C depending on the oxidation state. Along geotherms lower than 7 C/km typical for young subduction zones, no water is released up to 400 C. However, reduction of the rock causes release of small amounts of water. Metapsammopelitic rocks also store about 6 wt% H2O in minerals at 150 C. Considerable amounts of water are liberated by mineral reactions already in the temperature range 150-250 C also at the above mentioned low geotherms. This behavior determines the rheological characteristics of the upper oceanic crust during early subduction. If water is exclusively released in the sedimentary portion of the downgoing crust only this material gets weakened to be scraped off to form accretionary wedges. At geotherms of 15-20 C/km both lithologies show significant dehydration at very low metamorphic grade. For instance, in cold frontal paleoaccretionary prisms of the Chilean Coastal Cordillera metapelites by far dominate whereas in hotter basal accretionary prisms both low grade basic oceanic crust and continental sediments occur. We also hypothesize that accretionary wedge complexes with a clear dominance of sediments should not have formed in hot subduction zones typical for Precambrian Earth.

  16. LONG-TERM OUTCOME OF CENTRALLY LOCATED LOW-GRADE GLIOMA IN CHILDREN

    PubMed Central

    Terashima, Keita; Chow, Kevin; Jones, Jeremy; Ahern, Charlotte; Jo, Eunji; Ellezam, Benjamin; Paulino, Arnold C.; Okcu, M. Fatih; Su, Jack; Adesina, Adekunle; Mahajan, Anita; Dauser, Robert; Whitehead, William; Lau, Ching; Chintagumpala, Murali

    2014-01-01

    BACKGROUND: Optimal management of children with centrally located low-grade glioma (LGG) is unclear. A better understanding of the inherent risk factors along with the effects of interventions on long-term outcome can lead to reassessment of the current approaches to minimize long-term morbidity. Our goal was to reassess the current treatment strategies to gain a better understanding of the benefits and risks of different treatment approaches. A secondary goal was to determine whether BRAF-KIAA1549 (B-K) fusion is associated with a better PFS. METHODS: To reassess the current treatment strategies of centrally located LGG, we compared the long-term survival and morbidity of different treatment regimens. Medical records of patients primarily treated at Texas Children's Cancer and Hematology Center, Baylor College of Medicine between 1987 and 2008 were reviewed. Fluorescent in situ hybridization (FISH) for B-Kfusion/duplication was performed. RESULTS: Forty-seven patients with a median follow-up of 79 months were included in the analysis. The 5-year overall survival (OS) and progression-free survival (PFS) for all patients were 96% and 53%, respectively. The 5 year PFS for those treated initially with RT (12 patients, median age 11 years, range 3-15) and with chemotherapy (28 patients, median age 2 years, range 0-8) were 76% and 37%, respectively (log-rank test p = 0.02). Among children who progressed after chemotherapy, the 5-year PFS after salvage RT was 55%. Patients diagnosed at a younger age (<5yrs) were more likely to experience endocrine abnormalities (Fisher's Exact test, p < 0.00001). In 27 patients with qualified tissue sample, risk of progression is nearly 3 times higher with presence of B-K fusion/duplication compared to the absence of B-K fusion/duplication (HR 2.95, 95% CI: 0.83-10.51). CONCLUSIONS: Effective and durable tumor control was obtained with RT as initial treatment. In younger patients, chemotherapy can delay the use of RT; however, frequent progression and long-term morbidity are common. More effective and less toxic therapies are required in these patients, the majority of whom are long-term survivors. Our cohort confirmed the previous report of frequent B-K fusion in pilocytic astrocytoma, but did not find any significant association between this fusion and clinical outcomes. Molecular-targeting therapeutics for B-K fusion specifically or MAPK pathway are promising future treatment with potentially less toxic effect. SECONDARY CATEGORY: Clinical Neuro-Oncology.

  17. Molecular fingerprinting reflects different histotypes and brain region in low grade gliomas

    PubMed Central

    2013-01-01

    Background Paediatric low-grade gliomas (LGGs) encompass a heterogeneous set of tumours of different histologies, site of lesion, age and gender distribution, growth potential, morphological features, tendency to progression and clinical course. Among LGGs, Pilocytic astrocytomas (PAs) are the most common central nervous system (CNS) tumours in children. They are typically well-circumscribed, classified as grade I by the World Health Organization (WHO), but recurrence or progressive disease occurs in about 10-20% of cases. Despite radiological and neuropathological features deemed as classic are acknowledged, PA may present a bewildering variety of microscopic features. Indeed, tumours containing both neoplastic ganglion and astrocytic cells occur at a lower frequency. Methods Gene expression profiling on 40 primary LGGs including PAs and mixed glial-neuronal tumours comprising gangliogliomas (GG) and desmoplastic infantile gangliogliomas (DIG) using Affymetrix array platform was performed. A biologically validated machine learning workflow for the identification of microarray-based gene signatures was devised. The method is based on a sparsity inducing regularization algorithm l1l2 that selects relevant variables and takes into account their correlation. The most significant genetic signatures emerging from gene-chip analysis were confirmed and validated by qPCR. Results We identified an expression signature composed by a biologically validated list of 15 genes, able to distinguish infratentorial from supratentorial LGGs. In addition, a specific molecular fingerprinting distinguishes the supratentorial PAs from those originating in the posterior fossa. Lastly, within supratentorial tumours, we also identified a gene expression pattern composed by neurogenesis, cell motility and cell growth genes which dichotomize mixed glial-neuronal tumours versus PAs. Our results reinforce previous observations about aberrant activation of the mitogen-activated protein kinase (MAPK) pathway in LGGs, but still point to an active involvement of TGF-beta signaling pathway in the PA development and pick out some hitherto unreported genes worthy of further investigation for the mixed glial-neuronal tumours. Conclusions The identification of a brain region-specific gene signature suggests that LGGs, with similar pathological features but located at different sites, may be distinguishable on the basis of cancer genetics. Molecular fingerprinting seems to be able to better sub-classify such morphologically heterogeneous tumours and it is remarkable that mixed glial-neuronal tumours are strikingly separated from PAs. PMID:23947815

  18. Low-grade endometrial stromal sarcoma developing in a postmenopausal woman under toremifene treatment for breast cancer.

    PubMed

    Kashiyama, Tomoko; Oda, Katsutoshi; Kawana, Kei; Arimoto, Takahide; Kanetaka, Yukiko; Takazawa, Yutaka; Maeda, Daichi; Nakagawa, Shunsuke; Yano, Tetsu; Kozuma, Shiro

    2013-01-01

    Low-grade endometrial stromal sarcoma (ESS) is a rare neoplasm that is generally estrogen-receptor- and progesterone-receptor-positive and develops in premenopausal women. Although tamoxifen treatment is associated with an increased risk of ESS, the effect of other selective estrogen receptor modulators, including toremifene, on the risk of ESS is not clear. A 61-year-old postmenopausal woman was treated with toremifene as an adjuvant therapy for breast cancer. A cystic mass developed during the treatment, with gradual growth in the uterine myometrium. The patient was treated with hysterectomy and bilateral salpingo-oophorectomy, and the tumor was diagnosed as low-grade ESS (stage IA) with estrogen-receptor and progesterone-receptor. The patient discontinued toremifene and has been progression-free for 21 months. Our data suggest that toremifene might be associated with the development of ESS in certain patients through its estrogen-like effects in the uterus. PMID:22690656

  19. The use of dual growing rods to correct spinal deformity secondary to a low-grade spinal cord astrocytoma

    PubMed Central

    Kuhn, Elizabeth N.; Muthigi, Akhil; Frino, John; Powers, Alexander K.

    2015-01-01

    Pediatric intramedullary spinal cord astrocytomas are rare, and the majority are low grade, typically carrying a low risk of mortality, but a high risk of morbidity. Quality of life is, therefore, an important consideration in treating concomitant progressive kyphoscoliosis. Compared with fusion-based spinal stabilization, fusionless techniques may limit some complications related to early instrumentation of the developing spine. Another consideration is the timing of radiation therapy relative to both spinal maturity and spinal instrumentation. To date, there have been no reports of the use of a fusionless technique to treat spinal deformity secondary to an intramedullary spinal cord tumor. Herein, we report the use of fusionless spinal stabilization with dual growing rods in a boy with low-grade spinal cord astrocytoma after radiation therapy. PMID:26468485

  20. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity

    PubMed Central

    Cani, Patrice D.; Osto, Melania; Geurts, Lucie; Everard, Amandine

    2012-01-01

    Obesity is associated with metabolic alterations related to glucose homeostasis and cardiovascular risk factors. These metabolic alterations are associated with low-grade inflammation that contributes to the onset of these diseases. We and others have provided evidence that gut microbiota participates in whole-body metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders. Recently, we defined gut microbiota-derived lipopolysaccharide (LPS) (and metabolic endotoxemia) as a factor involved in the onset and progression of inflammation and metabolic diseases. In this review, we discuss mechanisms involved in the development of metabolic endotoxemia such as the gut permeability. We also discuss our latest discoveries demonstrating a link between the gut microbiota, endocannabinoid system tone, leptin resistance, gut peptides (glucagon-like peptide-1 and -2), and metabolic features. Finally, we will introduce the role of the gut microbiota in specific dietary treatments (prebiotics and probiotics) and surgical interventions (gastric bypass). PMID:22572877

  1. Incidental Diagnosis of an Asymptomatic Hydatid Cyst Through Low-Grade 18F-FDG Uptake in the Peripheral Rim.

    PubMed

    Kumar, Nandigam S; Barve, Ketaki; Joshi, Jyotsna; Basu, Sandip

    2015-12-01

    Here we present a case of an untreated, asymptomatic, pulmonary hydatid cyst incidentally diagnosed on the basis of atypically low-grade (18)F-FDG uptake in the peripheral rim and a minimal increase in uptake on dual-point (18)F-FDG PET/CT. The patient underwent (18)F-FDG PET/CT for characterization of a solitary lung lesion found on chest radiography and inconclusive findings on contrast-enhanced CT. Although the diagnosis was confirmed by a serum indirect hemagglutination assay positive for Echinococcus granulosus, the low-grade (18)F-FDG uptake in the context of the asymptomatic presentation was noteworthy, as it could be related to minimal active inflammation. Our case, together with similar previously published findings, leads to the hypothesis that inflammatory (18)F-FDG uptake may be an additional determinant of the cause of symptoms in these patients. PMID:26111709

  2. Studies on the production of ultra-clean coal by alkali-acid leaching of low-grade coals

    SciTech Connect

    Nabeel, A.; Khan, T.A.; Sharma, D.K.

    2009-07-01

    The use of low-grade coal in thermal power stations is leading to environmental pollution due to the generation of large amounts of fly ash, bottom ash, and CO{sub 2} besides other pollutants. It is therefore important to clean the coal before using it in thermal power stations, steel plants, or cement industries etc. Physical beneficiation of coal results in only limited cleaning of coal. The increasing environmental pollution problems from the use of coal have led to the development of clean coal technologies. In fact, the clean use of coal requires the cleaning of coal to ultra low ash contents, keeping environmental norms and problems in view and the ever-growing need to increase the efficiency of coal-based power generation. Therefore this requires the adaptation of chemical cleaning techniques for cleaning the coal to obtain ultra clean coal having ultra low ash contents. Presently the reaction conditions for chemical demineralization of low-grade coal using 20% aq NaOH treatment followed by 10% H{sub 2}SO{sub 4} leaching under reflux conditions have been optimized. In order to reduce the concentration of alkali and acid used in this process of chemical demineralization of low-grade coals, stepwise, i.e., three step process of chemical demineralization of coal using 1% or 5% aq NaOH treatment followed by 1% or 5% H{sub 2}SO{sub 4} leaching has been developed, which has shown good results in demineralization of low-grade coals. In order to conserve energy, the alkali-acid leaching of coal was also carried out at room temperature, which gave good results.

  3. Prospective Study of the Progression of Low-Grade Dysplasia in Ulcerative Colitis Using Current Cancer Surveillance Guidelines

    PubMed Central

    Zisman, Timothy L.; Bronner, Mary P.; Rulyak, Stephen; Kowdley, Kris V.; Saunders, Michael; Lee, Scott D.; Ko, Cynthia; Kimmey, Michael B.; Stevens, Allyn; Maurer, Josephine; Brentnall, Teresa A.

    2012-01-01

    Background The goal of this study was to assess the natural history of low-grade dysplasia and its risk of progression in ulcerative colitis (UC) patients by prospective endoscopic surveillance. Methods 42 UC patients with low-grade dysplasia (LGD) were followed prospectively using a uniform approach to surveillance colonoscopy with an average of 43 biopsies per exam. The interval between colonoscopies ranged from 312 months. Progression was defined as development of high-grade dysplasia (HGD) or cancer (CA) at subsequent colonoscopy or at colectomy. Univariate and multivariate analysis were performed to identify risk factors associated with progression. Results Patients were followed for an average of 3.9 years (range 113). Over that period 19% (8/42) of patients progressed to advanced neoplasia (2 cancers, 6 HGD) while 17% (7/42) had persistent LGD and 64% (27/42) had indefinite dysplasia or no dysplasia at the end of follow-up. Multivariate analysis demonstrated that the number of biopsies with low grade dysplasia at baseline was associated with an increased risk of progression to advanced neoplasia (RR-5.8, 95%CI (1.2926.04). Among the 15 patients who underwent colectomy, four were found to have higher grade neoplasia on their colectomy specimen that their pre-operative colonoscopy, and these patients were more likely to be nonadherent with recommendations for colectomy. Conclusions The majority (81%) of UC patients with LGD did not progress to higher grades of dysplasia during a 4 year follow-up. Patients with 3 or more biopsies demonstrating low grade dysplasia at a single colonoscopy were at increased risk for progression to advanced neoplasia. PMID:22508402

  4. Upgrading of consumer characteristics of granulated solid fuel from mixture of low-grade coal and biomass

    NASA Astrophysics Data System (ADS)

    Kuzmina, J. S.; Milovanov, O. Yu; Sinelshchikov, V. A.; Sytchev, G. A.; Zaichenko, V. M.

    2015-11-01

    Effect of torrefaction on consumer characteristics of fuel pellets made of low-grade and agricultural waste is shown. Data on the volatile content, ash content, calorific value and hygroscopicity for initial pellets and pellets, heat-treated at various temperatures are presented. The experimental study of the combustion process of initial and heat-treated pellets showed that torrefaction of pellets leads to a decreasing of the ignition temperature and an increasing of the efficiency of boiler plant.

  5. Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma.

    PubMed

    Duerinck, Johnny; Du Four, Stephanie; Sander, Wilhelm; Van Binst, Anne-Marie; Everaert, Hendrik; Michotte, Alex; Hau, Peter; Neyns, Bart

    2015-10-01

    Tyrosine kinase signaling through the vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor- ? (PDGFR-?) and KIT cell surface receptors mediates neo-angiogenesis and contributes to cancer cell survival in recurrent anaplastic and low-grade glioma. Thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma were treated with sunitinib malate, a small-molecule tyrosine kinase inhibitor of the VEGFR, PDGFR, and KIT receptors, in combination with lomustine. The most frequent grade 3 and 4 adverse events were fatigue, thrombocytopenia, neutropenia and lymphopenia. The best objective tumor response by Response Assessment in Neuro-Oncology (RANO) criteria was one complete response, one unconfirmed partial response and three cases of stable disease. The median progression-free survival was 1.8 months (95% confidence interval=1.0-2.7 months) with 6-month progression-free survival of 15% (95% confidence interval=0-35%). The median overall survival was 6.7 months (95% confidence interval=0.7-12 months). The investigated combination regimen of sunitinib and lomustine is well-tolerated but insufficiently active to warrant further investigation in an unselected population of patients with temozolomide-refractory recurrent anaplastic and low-grade glioma. PMID:26408725

  6. Separation and Extraction of Bismuth and Manganese from Roasted Low-Grade Bismuthinite and Pyrolusite: Thermodynamic Analysis and Sulfur Fixing

    NASA Astrophysics Data System (ADS)

    Zhan, Jing; Wang, Zhi-Jian; Zhang, Chuan-Fu; Hwang, Jiann-Yang; Xia, Chu-Ping

    2015-05-01

    A new environmentally friendly technology with higher recovery of bismuth is proposed to extract bismuth from low-grade bismuthinite and co-production MnSO4 from low-grade pyrolusite. The effects of simultaneous roasting process parameters on the sulfur-fixing rate and MnSO4 formation rate are investigated. Based on the Pourbaix diagram of metal-sulfur-oxygen system, the behavior of bismuth, manganese, and associated metal elements such ferrous, copper, lead, and sulfur in the bismuthinite and pyrolusite during roasting process is analyzed. The experimental results show that Bi in the ores can be converted into bismuth oxide or oxygen bismuth sulfate, and most of Mn in the ores can react with SO2 from bismuthinite to form MnSO4, which agree with thermodynamic analysis. A maximum of sulfur-fixing rate of 98.14% and MnSO4 formation rate of 70.2% are obtained under the conditions of 1.4 for the molar ratio of MnO2 to total sulfur in mixing ores of bismuthinite and pyrolusite ( n(MnO2)/ n(S)), 923 K for the roasting temperature, 2 h for roasting time, 140 L/h for air rate, and less than 74 ?m for particle size. The ultimate recovery rate of bismuth reaches 96.25% by selective leaching of the roasted product, purification of leaching solution, and hydrolysis, which is higher than the current applied technology for the low-grade bismuthinite.

  7. The use of proton therapy in the treatment of benign or low-grade pediatric brain tumors.

    PubMed

    Eaton, Bree R; Yock, Torunn

    2014-01-01

    Radiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade central nervous system tumors in children but is not without the risk of long-term treatment-related sequelae. Proton therapy (PRT) is an advanced RT modality with a unique dose-deposition pattern that allows for treatment of a target volume with reduced scatter dose delivered to normal tissues compared with conventional photon RT and is now increasingly utilized in children with the hope of mitigating radiation-induced late effects. This article reviews the current literature evaluating the use of PRT in benign and low-grade pediatric central nervous system tumors such as low-grade glioma, craniopharyngioma, and ependymoma. Multiple dosimetric studies support the use of PRT by demonstrating the ability of PRT to better spare critical structures important for cognitive development, endocrine function, and hearing preservation and to reduce the total body dose associated with second malignancy risk. Early clinical data demonstrate that PRT is well tolerated with rates of local tumor control comparable to conventional photon RT series, and long-term clinical data are awaited. PMID:25415686

  8. Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary.

    PubMed

    Bonome, Tomas; Lee, Ji-Young; Park, Dong-Choon; Radonovich, Mike; Pise-Masison, Cindy; Brady, John; Gardner, Ginger J; Hao, Ke; Wong, Wing H; Barrett, J Carl; Lu, Karen H; Sood, Anil K; Gershenson, David M; Mok, Samuel C; Birrer, Michael J

    2005-11-15

    Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype. PMID:16288054

  9. Effect of Modified Atmosphere Packaging and Vacuum Packaging on Quality Characteristics of Low Grade Beef during Cold Storage

    PubMed Central

    Hur, S. J.; Jin, S. K.; Park, J. H.; Jung, S. W.; Lyu, H. J.

    2013-01-01

    Many studies have been carried out with respect to packaging methods and temperature conditions of beef. However, the effects of packaging methods and temperature conditions on the quality characteristics have not been extensively studied in low-grade beef. Low-grade beef samples were divided into 3 groups (C: ziplock bag packaging, T1: vacuum packaging, and T2: modified atmosphere packaging (MAP), CO2/N2 = 3:7) and samples were stored at 4°C for 21 days. The water-holding capacity (WHC) was significantly lower in T1 than in the other samples up to 14 days of storage. The thiobarbituric acid reactive substances and volatile basic nitrogen values were significantly lower in T1 and T2 than in C after 7 to 14 days of storage. The total bacterial counts were significantly lower in T1 and T2 than in C after 14 days of storage. In a sensory evaluation, tenderness and overall acceptability were significantly higher in T1 and T2 than in C at the end of the storage period (21 days). We propose that the MAP method can improve beef quality characteristics of low-grade beef during cold storage. However, the beneficial effects did not outweigh the cost increase to implement MAP. PMID:25049769

  10. Innate lymphoid cells in inflammation and immunity.

    PubMed

    McKenzie, Andrew N J; Spits, Hergen; Eberl, Gerard

    2014-09-18

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles throughout the duration of immune responses, participating in the transition from innate to adaptive immunity and contributing to chronic inflammation. The proximity of ILCs to epithelial surfaces and their constitutive strategic positioning in other tissues throughout the body ensures that, in spite of their rarity, ILCs are able to regulate immune homeostasis effectively. Dysregulation of ILC function might result in chronic pathologies such as allergies, autoimmunity, and inflammation. A new role for ILCs in the maintenance of metabolic homeostasis has started to emerge, underlining their importance in fundamental physiological processes beyond infection and immunity. PMID:25238094

  11. Tertiary lymphoid structures in cancer and beyond.

    PubMed

    Dieu-Nosjean, Marie-Caroline; Goc, Jrmy; Giraldo, Nicolas A; Sauts-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. PMID:25443495

  12. Innate Lymphoid Cells in the Skin

    PubMed Central

    Kim, Brian S.

    2014-01-01

    Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis and pathologic inflammation. Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation. PMID:25339380

  13. The lymphoid follicle variant of dermatomyositis

    PubMed Central

    Pehl, Debora; Aronica, Eleonora; Schonenberg-Meinema, Dieneke; Schneider, Udo; Heppner, Frank L.; de Visser, Marianne; Goebel, Hans H.; Stenzel, Werner

    2014-01-01

    Objective: To investigate the clinical and morphologic spectrum of early adultonset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin. Methods: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed. Results: Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy. Conclusions: The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis. PMID:25340071

  14. The Role of Lymphoid Neogenesis in Allografts.

    PubMed

    Hsiao, H-M; Li, W; Gelman, A E; Krupnick, A S; Kreisel, D

    2016-04-01

    De novo induction of organized lymphoid aggregates at nonlymphoid sites has been observed in many chronic inflammatory conditions where foreign antigens such as infectious agents, autoantigens or alloantigens, persist. The prevailing opinion in the field of transplantation is that lymphoid neogenesis within allografts is detrimental to the establishment of immune tolerance. These structures, commonly referred to as tertiary lymphoid organs (TLOs), are thought to contribute to graft rejection by generating and propagating local alloimmune responses. However, recent studies have shown that TLOs rich in regulatory Foxp3(+) cells are present in long-term accepting allografts. The notion that TLOs can contribute to the local downregulation of immune responses has been corroborated in other chronic inflammation models. These findings suggest that contrary to previous suggestions that the induction of TLOs in allografts is necessarily harmful, the induction of "tolerogenic" TLOs may prove advantageous. In this review, we discuss our current understanding of how TLOs are induced and how they regulate immune responses with a particular focus on alloimmunity. PMID:26614734

  15. Advanced Energy and Water Recovery Technology from Low Grade Waste Heat

    SciTech Connect

    Dexin Wang

    2011-12-19

    The project has developed a nanoporous membrane based water vapor separation technology that can be used for recovering energy and water from low-temperature industrial waste gas streams with high moisture contents. This kind of exhaust stream is widely present in many industrial processes including the forest products and paper industry, food industry, chemical industry, cement industry, metal industry, and petroleum industry. The technology can recover not only the sensible heat but also high-purity water along with its considerable latent heat. Waste heats from such streams are considered very difficult to recover by conventional technology because of poor heat transfer performance of heat-exchanger type equipment at low temperature and moisture-related corrosion issues. During the one-year Concept Definition stage of the project, the goal was to prove the concept and technology in the laboratory and identify any issues that need to be addressed in future development of this technology. In this project, computational modeling and simulation have been conducted to investigate the performance of a nanoporous material based technology, transport membrane condenser (TMC), for waste heat and water recovery from low grade industrial flue gases. A series of theoretical and computational analyses have provided insight and support in advanced TMC design and experiments. Experimental study revealed condensation and convection through the porous membrane bundle was greatly improved over an impermeable tube bundle, because of the membrane capillary condensation mechanism and the continuous evacuation of the condensate film or droplets through the membrane pores. Convection Nusselt number in flue gas side for the porous membrane tube bundle is 50% to 80% higher than those for the impermeable stainless steel tube bundle. The condensation rates for the porous membrane tube bundle also increase 60% to 80%. Parametric study for the porous membrane tube bundle heat transfer performance was also done, which shows this heat transfer enhancement approach works well in a wide parameters range for typical flue gas conditions. Better understanding of condensing heat transfer mechanism for porous membrane heat transfer surfaces, shows higher condensation and heat transfer rates than non-permeable tubes, due to existence of the porous membrane walls. Laboratory testing has documented increased TMC performance with increased exhaust gas moisture content levels, which has exponentially increased potential markets for the product. The TMC technology can uniquely enhance waste heat recovery in tandem with water vapor recovery for many other industrial processes such as drying, wet and dry scrubber exhaust gases, dewatering, and water chilling. A new metallic substrate membrane tube development and molded TMC part fabrication method, provides an economical way to expand this technology for scaled up applications with less than 3 year payback expectation. A detailed market study shows a broad application area for this advanced waste heat and water recovery technology. A commercialization partner has been lined up to expand this technology to this big market. This research work led to new findings on the TMC working mechanism to improve its performance, better scale up design approaches, and economical part fabrication methods. Field evaluation work needs to be done to verify the TMC real world performance, and get acceptance from the industry, and pave the way for our commercial partner to put it into a much larger waste heat and waste water recovery market. This project is addressing the priority areas specified for DOE Industrial Technologies Program's (ITP's): Energy Intensive Processes (EIP) Portfolio - Waste Heat Minimization and Recovery platform.

  16. Fluid composition and mineral equilibria in low grade metamorphic rocks, Bündnerschiefer, Switzerland

    NASA Astrophysics Data System (ADS)

    Miron, G. D.; Wagner, T.; Wälle, M.; Heinrich, C. A.

    2012-04-01

    The composition of fluid inclusions (FI) hosted in quartz veins from low-grade metamorphic rocks of the Bündnerschiefer (two locations near Thusis and Schiers that represent subgreenschist and lower greenschist facies conditions, respectively), Swiss Alps, was determined by combination of microthermometry and LA-ICPMS microanalysis. Elongate-blocky quartz and euhedral quartz crystals were sampled form two sets of veins, which are foliation-parallel and open fissure veins that crosscut the main foliation. The host rocks are organic-rich metapelites, that in places contain relatively high amounts of carbonate. Several metamorphic temperature indicators were used to determine the temperature and pressure during metamorphism of the host rocks. These included the Kübler index (Kübler & Jaboyedoff 2000), Raman spectroscopy on carbonaceous material (Beyssac et al., 2002), Na-Mg and Li-Mg fluid solute geothermometry (Giggenbach, 1988; Kharaka & Mariner, 1989) and mineral assemblages. The geothermometers point to equilibrium temperatures around 320±20 °C (Thusis) and 250±20 °C (Schiers). The results of pseudosection modeling show very close agreement with the pressure-temperature conditions that were derived from conventional geothermobarometry. The FI bulk salinity and homogenization temperatures are 4±0.2 wt% eqv. NaCl and 122-140 °C for Thusis, and 2±0.2 wt% and 82-86 °C at Schiers. Most of the important rock-forming elements have been successfully determined in individual FI, with consistent concentrations obtained for well-constrained fluid inclusion assemblages. The FI contain measurable concentrations of Na, K, Rb, Cs, Li, Ca, Mg, Al, Mn, Sr, Ba, B, As, B, Zn, Pb, Cu and S. Typical concentrations are 30-40 ppm Al, 5-7 ppm Mg, 300-400 ppm Ca, 3-5 ppm Mn, and 300-350 ppm S for FI from Thusis. Concentrations for most elements are roughly half an order of magnitude lower for FI from Schiers. The total element concentrations are lower compared with data from similar metamorphic vein settings (Yardley et al., 1993; Yardley, 2005). This likely reflects the lower salinity of fluids in the Bündnerschiefer veins, which exerts a major control on those elements that are complexed by chloride. Combining fluid inclusion isochores with independent geothermometers results in pressure estimates of 2.8-3.8 kbars for Thusis, and around 3.4 kbars for Schiers. The geothermal gradient decreases from the southern location (27-22 °C/km: Thusis) to the northern location (19 °C/km: Schiers), in agreement with their position during metamorphism. The fluid composition data, in conjunction with metamorphic indicators and petrological modeling, demonstrate that fluid-rock equilibrium was attained during metamorphism and vein formation. Fluid composition and pressure-temperature conditions remained essentially unchanged during the evolution of the vein systems. The veins evolved as rock-buffered closed systems, due to the low permeability of the organic-rich metapelites.

  17. Ovarian serous tumors of low malignant potential with nodal low-grade serous carcinoma.

    PubMed

    Djordjevic, Bojana; Malpica, Anais

    2012-07-01

    Serous tumor of low malignant potential (SLMP) and low-grade serous carcinoma (LGSC) are part of one biological continuum, whereby SLMP can transform into LGSC. It has been suggested that some nodal SLMPs arise from nodal endosalpingiosis and evolve independently in lymph nodes (rather than being related to the ovarian primary). In this article, we present the clinicopathologic features of 5 cases of nodal LGSC presenting in association with ovarian SLMP. Clinical information was obtained from the patients' charts. Pathologic features of the nodal LGSC, including lymph node location, size of and extent of involvement of tumor, architectural pattern, degree of cytologic atypia, mitotic index, and presence of psammoma bodies, were recorded. Ovarian SLMPs were noted for laterality, size, presence of surface excrescences, microinvasion, and micropapillary/cribriform pattern and for presence of autoimplants, invasive, and noninvasive implants. The distribution of any lymph nodes with nodal endosalpingiosis or SLMPs was also recorded. Patients ranged in age from 28 to 68 years (median, 32 y). In 4 cases, the diagnosis of nodal LGSC occurred at a different time from that of the ovarian SLMPs, ranging from 7 months before to 5 months after the ovarian tumor diagnosis. Nodal LGSC was detected in supraclavicular (2 cases), cervical, intramammary, and periaortic lymph nodes (1 case each). The gross lymph node size ranged from 0.9 to 2.5 cm (median, 1.3 cm). The tumors either replaced the entire lymph node or were found diffusely involving subcapsular and medullary sinuses or lymph node cortices. Tumor cells showed typical cytologic features of LGSC and no mitotic activity. In 2 cases, however, focal pleomorphic cells and 1 mitosis per 10 HPF were noted. Psammoma bodies were identified in all cases. When immunohistochemical analysis was performed, all tumors exhibited a profile in keeping with Mllerian origin. All ovarian tumors were well sampled and ranged in size from 0.1 to 13 cm (median, 2.5 cm). No ovarian SLMP tumors showed the micropapillary/cribriform pattern, whereas only focal microinvasion was detected in 3 cases. Four tumors had surface excrescences. All cases had noninvasive implants, and a single case also had invasive implants. Lymph node dissection was performed in 2 cases, revealing extensive endosalpingiosis in pelvic and periaortic lymph nodes and SLMP in pelvic lymph nodes. In 1 additional case, a single lymph node was sampled, revealing a nodal SLMP. Clinical follow-up ranged from 2 to 14 years (median, 9 y). All patients received postoperative chemotherapy. None of the patients experienced recurrence in pelvic or abdominal soft tissue. Two patients are free of disease. However, 2 patients, one with cervical and another with supraclavicular nodal LGSC, had recurrences at these sites and subsequently succumbed to metastatic disease. Both of these patients had pelvic and periaortic nodal SLMP and extensive nodal endosalpingiosis. Another patient, originally with supraclavicular LGSC, developed pelvic and abdominal lymphadenopathy, and is currently alive with disease. For the first time, we present a case series of patients with ovarian SLMP who, despite any evidence of LGSC in the pelvis or any pelvic recurrences, developed extrapelvic/extra-abdominal nodal LGSC. These patients also had endosalpingiosis and SLMP in pelvic and periaortic lymph nodes, suggesting that SLMP/LGSC tumors in lymph nodes may arise independently of the ovarian primary, progress along their own timeline, and undergo metastatic spread. Therefore, in patients with ovarian SLMP and extensive pelvic/periaortic nodal endosalpingiosis and/or SLMP, examination and follow-up of extrapelvic lymph nodes are warranted, even if the ovarian tumor lacks high-risk features of recurrence. PMID:22613998

  18. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.

    PubMed

    Gasteiger, Georg; Fan, Xiying; Dikiy, Stanislav; Lee, Sue Y; Rudensky, Alexander Y

    2015-11-20

    Innate lymphoid cells (ILCs) contribute to barrier immunity, tissue homeostasis, and immune regulation at various anatomical sites throughout the body. How ILCs maintain their presence in lymphoid and peripheral tissues thus far has been unclear. We found that in the lymphoid and nonlymphoid organs of adult mice, ILCs are tissue-resident cells that were maintained and expanded locally under physiologic conditions, upon systemic perturbation of immune homeostasis and during acute helminth infection. However, at later time points after infection, cells from hematogenous sources helped to partially replenish the pool of resident ILCs. Thus, ILCs are maintained by self-renewal in broadly different microenvironments and physiological settings. Such an extreme "sedentary" lifestyle is consistent with the proposed roles of ILCs as sentinels and local keepers of tissue function. PMID:26472762

  19. Stroma cell priming in enteric lymphoid organ morphogenesis

    PubMed Central

    Ferreira, Manuela; Domingues, Rita G.; Veiga-Fernandes, Henrique

    2012-01-01

    The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs (SLO) occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional lymphoid tissue inducer (LTi) cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to SLO formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood. Recently, new findings revealed early phases of SLO development putting emphasis on mesenchymal and lymphoid tissue initiator cells. Herein we discuss the main tenets of enteric lymphoid organs genesis and focus in the most recent findings that open new perspectives to the understanding of the early phases of lymphoid morphogenesis. PMID:22837761

  20. Correlation of tumor-infiltrating lymphocytes with bladder cancer recurrence in patients with solitary low-grade urothelial carcinoma.

    PubMed

    Krpina, Kristian; Babarovi?, Emina; Jonji?, Nives

    2015-10-01

    The aim of the present study was to correlate tumor-infiltrating lymphocytes (TIL) with bladder cancer recurrence in patients with solitary low-grade non-muscle-invasive bladder cancer (NMIBC). We retrospectively identified from the institutional database 115 patients with solitary low-grade NMIBC after transurethral resection (TURBT) without adjuvant therapy and with complete follow-up, between 1996 and 2006. Tumor specimens were retrieved and tissue microarrays were constructed. Patients were divided in two groups: those who developed recurrent disease (n?=?69) and those without recurrence (n?=?46) during a follow-up period of a minimum of 5 years. Immunohistochemical staining for TIL with anti-CD3, CD4, CD8, CD20, CD56, CD68, and granzyme B (GrB) was performed. Student's t test, Mann-Whitney U test, as well as uni- and multivariate analyses were applied to compare the two patient groups. TIL were predominantly observed in cancer stroma. The number of CD3+ and CD8+ lymphocytes observed in the non-recurrent group of patients was lower than that in recurrent patients (p?=?0.0001, p?=?0.0002, respectively). Also, in uni- and multivariate analyses, levels of CD3+ TIL (OR?=?5.4035; p?=?0.0001 and OR?=?5.8280; p?=?0.0102) and CD8+ TIL (OR?=?3.2857; p?=?0.0036 and OR?=?5.3257; p?=?0.0092) showed prognostic value with regard to NMIBC recurrence. Our results suggest that CD3+ and CD8+ TIL are predictive of bladder cancer recurrence in patients with solitary low-grade NMIBC which might facilitate identification of patients with higher risk of recurrence. However, prospective validating studies have to confirm these results before immunohistochemical staining for CD3 and CD8 TIL can be included in the clinical workup of these patients. PMID:26215559

  1. Missed low-grade infection in suspected aseptic loosening has no consequences for the survival of total hip arthroplasty

    PubMed Central

    Boot, Willemijn; Moojen, Dirk Jan F; Visser, Els; Lehr, A Mechteld; De Windt, Tommy S; Van Hellemondt, Gijs; Geurts, Jan; Tulp, Niek J A; Schreurs, B Wim; Burger, Bart J; Dhert, Wouter J A; Gawlitta, Debby; Vogely, H Charles

    2015-01-01

    Background and purpose Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 413% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long-term implant survival was investigated. Patients and methods Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. Results 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. Interpretation Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival. PMID:26364842

  2. The development of adult innate lymphoid cells.

    PubMed

    Yang, Qi; Bhandoola, Avinash

    2016-04-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  3. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation)

    PubMed Central

    Nita, Ma?gorzata; Ascaso, Francisco J.; Huerva, Valentn

    2014-01-01

    The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation) process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH) and facilitates chronic inflammation mediated by C-reactive protein (CRP). Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2) and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages); however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages). PMID:25214719

  4. Subclinical-Dose Endotoxin Sustains Low-Grade Inflammation and Exacerbates Steatohepatitis in High-Fat Diet-Fed Mice.

    PubMed

    Guo, Honghui; Diao, Na; Yuan, Ruoxi; Chen, Keqiang; Geng, Shuo; Li, Mingsong; Li, Liwu

    2016-03-01

    Subclinical circulating bacterial endotoxin LPS has been implicated as an important cofactor in the development and progression of nonalcoholic steatohepatitis, but the underlying mechanisms remain unclear. In this study, we demonstrated that 4-wk injection with superlow-dose LPS significantly promoted neutrophil infiltration and accelerated nonalcoholic steatohepatitis progression, including exacerbated macrovesicular steatosis, inflammation, and hepatocyte ballooning in high-fat diet-fed apolipoprotein E knockout mice. This effect could sustain for a month after stoppage of LPS injection. LPS also significantly increased numbers of apoptotic nuclei in hepatocytes and expressions of proapoptotic regulators. Moreover, LPS sustained the low-grade activation of p38 MAPK and inhibited the expression of the upstream MAPK phosphatase 7. By applying selective inhibitors, we demonstrated that the activation of p38 MAPKs is required for neutrophil migration induced by superlow-dose LPS in vitro. Together, these data suggest that superlow-dose LPS may sustain the low-grade activation of p38 MAPKs and neutrophil infiltration, leading to the exacerbation of steatohepatitis. PMID:26810228

  5. Multiple low-grade sarcomas of fibroblastic type in the setting of HIV and acquired epidermodysplasia verruciformis.

    PubMed

    Dosal, Jacquelyn; Nelson, Ann M; Shelling, Michael; Romaguera, Rita; Poulos, Evangelos; Alonso-Llamazares, Javier

    2014-10-01

    A 46-year-old white male with a history of HIV (CD4 245), acquired epidermodysplasia verruciformis, anal carcinoma in situ, hepatitis B and C presented with 3 asymptomatic, nontender, firm pink/skin-colored nodules involving the arm, left lateral leg, and right third finger. One year later, he developed a similar lesion on his right medial lower leg. Excisional biopsy of one of the lesions showed an atypical spindle cell neoplasm of the dermis compatible with a low-grade sarcoma of fibroblastic origin. Testing for human herpes virus-8, 23 human papillomavirus types, Epstein-Barr virus, and FUS fusion protein were negative. The patient underwent diagnostic imaging with computed tomography scans of the chest, abdomen, and pelvis along with positron emission tomography scan to ensure that there was no other occult primary tumor, all of which were negative. The lesions were excised and have not recurred with 3 years of follow-up. The best histopathologic term for these lesions is multiple low-grade sarcomas of fibroblastic phenotype. They have been proven to be nonaggressive, with little or no metastatic potential. This is a neoplastic process that has not been well defined in the literature. To our knowledge, there are no previous reports of these lesions occurring in multiple sites or in an HIV-positive patient. PMID:23759878

  6. Effects of Sodium Citrate on the Ammonium Sulfate Recycled Leaching of Low-Grade Zinc Oxide Ores

    NASA Astrophysics Data System (ADS)

    Yang, Kun; Li, Shi-wei; Zhang, Li-bo; Peng, Jin-hui; Ma, Ai-yuan; Wang, Bao-bao

    2016-03-01

    The effects of sodium citrate on ammonium sulfate recycled leaching of low-grade zinc oxide ores were studied. By applying various kinds of detection and analysis techniques such as chemical composition analysis, chemical phase method, scanning electron microscopy and energy dispersive spectrum (SEM/EDS), X-ray diffraction (XRD) and Fourier-transforming infrared spectrum (FT-IR), zinc raw ore, its leaching slag and the functional mechanism of sodium citrate were investigated. Based on a comprehensive analysis, it can be concluded that in contrast to hemimorphite (Zn4Si2O7(OH)2 · H2O), amorphous smithsonite (ZnCO3) and zinc silicate (Zn2SiO4) prove to be refractory phases under ammonium sulfate leaching, while sodium citrate has a better chelating action with the refractory phases, resulting in a higher zinc leaching rate. Under conditions of [NH3]/[NH3]T molar ratio being 0.5, [NH3]T being 7.5 mol/L, [Na3C6H5O7] being 0.2 mol/L, S/L ratio being 1:5, temperature being 303 K, holding time being 1 h in each of the two stages, and stirring rate being 300 rpm, the leaching rate of zinc reached 93.4%. In this article, sulfate ammonium recycled technology also reveals its unique advantage in processing low-grade zinc oxide ores accompanied by high silicon and high alkaline gangue.

  7. Amyloid-rich low grade adenocarcinoma of the parotid: fine-needle aspiration cytology with histologic correlations.

    PubMed

    Yang, Grace C H; Kuhel, William I; Scognamiglio, Theresa

    2014-09-01

    Amyloid deposits are unexpected in salivary gland tumors. A 60-year-old woman presented with a 1.8 cm, slow-growing parotid mass. Both fine-needle aspiration and frozen section were misinterpreted as pleomorphic adenoma. The final pathology was amyloid-rich low grade adenocarcinoma of the parotid gland. The aspirates consisted of three components: mucin, amyloid, and tumor cells. The mucin was unusually thick, stringy, and metachromatic. The amyloid presented as innumerable concretions scattered solitarily or in small jigsaw puzzle-like aggregates, individually wrapped by tumor cells. The tumor cells had bland oval nuclei and scant-to-abundant cytoplasm, arranged in loosely cohesive small sheets. On histology, the tumor cells were arranged in interconnecting monolayered glands of a wide range of size with small patches of cellular regions composed of plump tumor cells. As the luminal mucin and amyloid deposits enlarged, the lining tumor cells became thin and flat. The glandular lumen molded amyloid concretions into different shapes and sizes. Atrophic or pyknotic tumor cells outlined the amyloid concretions with concentric laminations, reminiscent of corpora amylacea. Alcian blue positive luminal mucin, associated with newly formed amyloid, was present in mucinous regions of the tumor. This is the first description of cytologic features of amyloid-rich low grade adenocarcinoma of the parotid and the second case in the pathology literature. The literature of amyloid-rich tumors was reviewed and the implication of the presence of abundant amyloid on the death of tumor cells suggested. PMID:24550230

  8. Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling

    PubMed Central

    Dula, Stacey B.; Jecmenica, Mladen; Wu, Runpei; Jahanshahi, Pooya; Verrilli, Gretchen M.; Carter, Jeffrey D.; Brayman, Kenneth L.; Nunemaker, Craig S.

    2010-01-01

    Summary In obesity and the early stages of type 2 diabetes (T2D), pro-inflammatory cytokines are mildly elevated in the systemic circulation. This low-grade systemic inflammation exposes pancreatic islets to these circulating cytokines, but at levels ~1001000x lower than seen within the islet during insulitis, which have not been well described. We examined mouse islets treated overnight with a low-dose cytokine combination commonly associated with inflammation (TNF-alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using intracellular calcium ([Ca2+]i), a key component of insulin secretion and cytokine signaling. Cytokine-treated islets demonstrated several features that suggested dysfunction including excess [Ca2+]i in low physiological glucose (3mM), reduced responses to glucose stimulation, and disrupted [Ca2+]i oscillations. Interestingly, islets taken from young db/db mice showed similar disruptions in [Ca2+]i dynamics as cytokine-treated islets. Additional studies of control islets showed that the cytokine-induced elevation in basal [Ca2+]i was due to both greater calcium influx through L-type-calcium-channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these cytokine-induced disruptions could be reproduced by SERCA blockade. Our data suggest that chronic low-grade inflammation produces circulating cytokine levels that are sufficient to induce beta-cell dysfunction and may play a contributing role in beta-cell failure in early T2D. PMID:20800281

  9. Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling.

    PubMed

    Dula, Stacey B; Jecmenica, Mladen; Wu, Runpei; Jahanshahi, Pooya; Verrilli, Gretchen M; Carter, Jeffrey D; Brayman, Kenneth L; Nunemaker, Craig S

    2010-01-01

    In obesity and the early stages of type 2 diabetes (T2D), proinflammatory cytokines are mildly elevated in the systemic circulation. This low-grade systemic inflammation exposes pancreatic islets to these circulating cytokines at much lower levels than seen within the islet during insulitis. These low-dose effects have not been well described. We examined mouse islets treated overnight with a low-dose cytokine combination commonly associated with inflammation (TNF-alpha, IL-1 beta, and IFN-gamma). We then examined islet function primarily using intracellular calcium ([Ca(2+)](i)), a key component of insulin secretion and cytokine signaling. Cytokine-treated islets demonstrated several features that suggested dysfunction including excess [Ca(2+)](i) in low physiological glucose (3mM), reduced responses to glucose stimulation, and disrupted [Ca(2+)](i) oscillations. Interestingly, islets taken from young db/db mice showed similar disruptions in [Ca(2+)](i) dynamics as cytokine-treated islets. Additional studies of control islets showed that the cytokine-induced elevation in basal [Ca(2+)](i) was due to both greater calcium influx through L-type-calcium-channels and reduced endoplasmic reticulum (ER) calcium storage. Many of these cytokine-induced disruptions could be reproduced by SERCA blockade. Our data suggest that chronic low-grade inflammation produces circulating cytokine levels that are sufficient to induce beta-cell dysfunction and may play a contributing role in beta-cell failure in early T2D. PMID:20800281

  10. Cognitive function after radiotherapy for supratentorial low-grade glioma: A North Central Cancer Treatment Group prospective study

    SciTech Connect

    Laack, Nadia N.; Brown, Paul D. . E-mail: brown.paul@mayo.edu; Ivnik, Robert J.; Furth, Alfred F. M.S.; Ballman, Karla V.; Hammack, Julie E.; Arusell, Robert M.; Shaw, Edward G.; Buckner, Jan C.

    2005-11-15

    Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Methods and Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Results: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Conclusions: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

  11. Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom.

    PubMed

    Meguins, Lucas Crociati; Adry, Rodrigo Antnio Rocha da Cruz; Silva Jnior, Sebastio Carlos da; Pereira, Carlos Umberto; Oliveira, Jean Gonalves de; Morais, Dionei Freitas de; Arajo Filho, Gerardo Maria de; Marques, Lcia Helena Neves

    2015-11-01

    Objective To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome.Method A retrospective study was conducted with patients with temporal low-grade gliomas (LGG).Results Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 8.4 (9-68 years). The mean age at seizure onset was 25.7 9.2 (11-66 years). Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6%) were Engel I; seventeen (26.2%) Engel II; four (6.2%) Engel III and two (3.1%) Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6%) with total resection and in only 3 (33.3%) patients with partial resection.Conclusion Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom. PMID:26517215

  12. Crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder.

    PubMed

    Sethi, Sanjeev; Cuiffo, Barry P; Pinkus, Geraldine S; Rennke, Helmut G

    2002-01-01

    Intracellular crystal formation in histiocytes in multiple myeloma and other lymphoproliferative disorders is an uncommon presentation. In all cases, crystal formation is associated with accumulation of histiocytes containing light chain or immunoglobulin inclusions, and the disorder has been termed crystal-storing histiocytosis. We report a case of crystal-storing histiocytosis affecting the kidney with prominent infiltration of the mesangium by large mononuclear and multinuclear cells that contained eosinophilic crystalline material in the setting of a low-grade B-cell lymphoproliferative disorder. The interstitium did not contain similar crystal-containing histiocytes. On electron microscopy, the mononuclear and multinuclear cells in the mesangium were filled with rhomboid and needle-shaped crystals. Immunofluorescence studies showed the material to be positive for lambda light chains but negative for kappa light chains. To our knowledge, this is the first report of crystal-storing histiocytosis involving the kidney in a low-grade B-cell lymphoproliferative disorder with an immunophenotype of a marginal zone lymphoma and of exclusive expansion of the mesangium by infiltrating histiocytes containing needle-shaped and rhomboid crystals that were positive for lambda light chains. We report this case to illustrate an unusual finding of mesangial infiltration by crystal-storing histiocytes, and we review the literature of renal involvement by crystal-storing histiocytosis and crystal deposition in lymphoproliferative disorders. PMID:11774118

  13. Therapeutic Lymphoid Organogenesis in the Tumor Microenvironment.

    PubMed

    Weinstein, Aliyah M; Storkus, Walter J

    2015-01-01

    The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine- and cytokine-signaling pathways such as CCR7, CXCR5, lymphotoxin, and IL-36, which are involved in the generation of secondary lymphoid organs and effector immune responses, are now recognized as having value both as prognostic factors and as immunomodulatory therapeutics in the context of cancer. Furthermore, when produced in the TME, these mediators have been shown to promote the recruitment of immune cells, including T cells, B cells, dendritic cells (DCs), and other specialized immune cell subsets such as follicular DCs and T follicular helper cells, in association with the formation of "tertiary" lymphoid structures (TLSs) within or adjacent to sites of disease. Although TLSs are composed of a heterogeneous collection of immune cell types, whose composition differs based on cancer subtype, the qualitative presence of TLSs has been shown to represent a biomarker of good prognosis for cancer patients. A comprehensive understanding of the role each of these pathways plays within the TME may support the rational design of future immunotherapies to selectively promote/bolster TLS formation and function, leading to improved clinical outcomes across the vast range of solid cancer types. PMID:26216634

  14. Transcriptional regulation of innate lymphoid cell fate.

    PubMed

    Serafini, Nicolas; Vosshenrich, Christian A J; Di Santo, James P

    2015-07-01

    Innate lymphoid cells (ILCs) are a recently described family of lymphoid effector cells that have important roles in immune defence, inflammation and tissue remodelling. It has been proposed that ILCs represent 'innate' homologues of differentiated effector T cells, and they have been categorized into three groups namely, ILC1s, ILC2s and ILC3s on the basis of their expression of cytokines and transcription factors that are typically associated with T helper 1 (T(H)1)-, T(H)2- and T(H)17-type immune responses, respectively. Indeed, remarkable similarity is seen between the specific transcription factors required for the development and diversification of different ILC groups and those that drive effector T cell differentiation. The recent identification of dedicated ILC precursors has provided a view of the mechanisms that control this first essential stage of ILC development. Here, we discuss the transcriptional mechanisms that regulate ILC development and diversification into distinct effector subsets with key roles in immunity and tissue homeostasis. We further caution against the current distinction between 'helper' versus 'killer' subsets in the evolving area of ILC nomenclature. PMID:26065585

  15. Lymphoid Infiltrates in B Cell Non Hodgkins Lymphoma: Comparing Nuclear Characteristics between Lymph Node and Bone Marrow; and Evaluating Diagnostic Features of Bone Marrow Infiltrates in Paraffin Embedded Tissues

    PubMed Central

    Deverell, Mark H.; Best, Elizabeth; Salisbury, Jonathan R.

    1997-01-01

    Distinguishing non Hodgkins lymphoma from benign lymphoid aggregates in bone marrow is well recognised to be difficult. Our objective was to evaluate nuclear morphology, and to perform morphometry on benign and neoplastic lymphoid infiltrates, to establish if objective criteria were of value in the diagnosis of neoplasia. By comparing neoplastic infiltrates in bone marrow with infiltrates in lymph nodes, the validity of grading non Hodgkins lymphoma on the basis of bone marrow histology alone was assessed. 82 cases of B cell non Hodgkins lymphoma (44 low grade and 38 high grade), known to have both lymph node and bone marrow involvement at the time of presentation, were compared with bone marrow trephines containing reactive lymphoid infiltrates. The results suggest that in paraffin embedded tissue from bone marrow trephines, nuclear morphology, nuclear area and the nuclear contour index cannot, in most cases, be used to distinguish reactive from neoplastic lymphoid infiltrates although mean nuclear area supports a diagnosis of a neoplastic infiltrate if it can be shown that the nuclei are larger than would be expected in reactive infiltrates. Such differences are subtle and often not appreciable without the use of quantitative techniques. The frequent occurrence of discordant infiltrates in high grade lymphomas means grading of lymphoma on the basis of bone marrow appearances is often unrealistic. PMID:9283039

  16. Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

    SciTech Connect

    Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary S.; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

    2014-08-01

    Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy{sub RBE} (48.6-54 Gy{sub RBE}). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy{sub RBE} to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

  17. The optimisation of stope leaching: a laboratory investigation into the extraction of uranium from a low-grade ore

    NASA Astrophysics Data System (ADS)

    Penman, Kristina Mary

    Nuclear power continues to make an important contribution to energy production in many countries around the world. Uranium mining is the first step in the production cycle of nuclear power. In order to enable low-grade uranium ore bodies to be developed as economically viable resources, low input mining techniques, such as stope leaching, are gaining interest. This thesis presents the results of research undertaken into the optimisation of stope leaching from a low grade uranium ore. Stope leaching was simulated in the laboratory by submitting crushed ore samples to successive saturated (flooding) and unsaturated (rest period) cycles. Experiments were carried out over a 52 week period using seven different protocols. The effects of rest period and lixiviant composition on uranium extraction rates were investigated. Rest period was varied by flooding at weekly, twice weekly, 2 weekly and 4 weekly intervals.. Four different lixiviants were investigated, tap water, Fe(III) sulfate, a nutrient solution and recycled leachate. Maximum uranium extractions over 52 weeks were: 57.7% for Fe(III) sulfate lixiviant with a 2 week rest period and 57.4% for tap water with a 4 week rest period. The introduction (via the lixiviant) or development (via oxidation of accessory pyrite) of low pH and Fe(III) and sulfate-rich interstitial water is thought to have provided conditions conducive to uranium oxidation and dissolution. The 4 week rest period is considered to have provided sufficient time for microbially assisted pyrite oxidation to develop similar conditions in the interstitial water as were provided by the addition of a Fe(III) sulfate lixiviant. All other protocols lead to less than 35% uranium extraction. Shorter rest periods did not allow time for sufficient pyrite oxidation to occur and the addition of a nutrient solution buffered pH which did not favour uranium dissolution. These findings have significant implications for low-grade uranium recovery by demonstrating that extraction achieved through the use of costly oxidising agents can be attained, in the same time frame, by using tap water and decreasing the number of cycles..

  18. Feasibility of total body irradiation in chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphomas.

    PubMed

    Roncadin, M; Arcicasa, M; Bortolus, R; Trov, M G; Carbone, A; Tirelli, U; De Paoli, A; Franchin, G; Grigoletto, E

    1991-01-01

    Combined total body irradiation (TBI) and Prednimustine were prospectively evaluated in 30 patients affected either with chronic lymphocytic leukemia (CLL) or with low-grade non-Hodgkin's lymphoma (NHL) eleven patients were previously treated. Between January 1984 and May 1987, 20 evaluable patients with CLL, median age 66 years (range 43-82), classified according to Rai (4 in stage I, 10 in stage II, 4 in stage III, 2 in stage IV) and 10 evaluable patients with NHL low-grade malignancy according to the Working Formulation, Stages III and IV, median age 54 years (range 32-71) were treated using a 6 MeV Linear Accelerator, applying two opposite alternating fields including total body, with a fraction of 15 cGy, 2 fractions weekly (3-day interval) for a total dose of 150 cGy given over 5 weeks. Prednimustine (100 mg/m2, orally, for 5 consecutive days, every 3-4 weeks, for 6-9 courses) was administered 2 months after TBI treatment, as consolidation therapy. By May 1989, a total of 85% hematological responses (defined as normalization of the differential white cell count, of the total blood cell count and of bone marrow infiltration) were obtained after combined treatment in CLL patients; moreover 3 CR (according to the WHO criteria), 75% with splenomegaly reduction and 40% with lymphadenopathy reduction were seen. Ninety percent objective responses (5 CR and 4 PR) were observed in the NHL patients, with 50% having splenomegaly reduction and 67% lymphadenopathy reduction. The median response time in the two groups was, respectively, 14 and 23 months. The overall toxicity (WHO grades 1,2,3,4) after combined treatment was 65% and 70% in the two patient groups. WHO grade III toxicity, completely reversible, was verified in only 16.6% of the cases; all cases, except one, were previously treated. Additionally, 1 toxic death (grade IV thrombocytopenia and leukopenia) was observed in a heavily pretreated patient affected with CLL after TBI alone. Prednimustine regimen was generally well tolerated. The high response rate and acceptable toxicity, confirms the feasibility and the usefulness of TBI in the context of a combined treatment for CLL and low-grade NHL patients. However in order to further reduce the severe toxic side effects, observed in one patient, white blood cells and platelet count should be plotted and monitored carefully, particularly in pretreated patients. PMID:1884246

  19. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

  20. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

  1. Overall survival in adult patients with low-grade, supratentorial glioma: Ten years follow up at a single institution

    PubMed Central

    Kashi, Amir Shahram Yousefi; Rakhsha, Afshin; Houshyari, Mohammad

    2015-01-01

    Background: Low-grade gliomas (LGGs) are the second most prevalent type of primary brain tumors in adults. The prognosis for LGGs can differ according to the clinical-pathological prognostic factors determined during diagnosis and treatment. The purpose of this study was to identify 10-year, disease-free survival (DFS), 10-year overall survival (OS), and related clinical-pathological prognostic factors of adult patients with supratentorial, low-grade gliomas who were treated with or without surgery and radiation therapy. Methods: The study included 110 patients who were confirmed to have low-grade, supratentorial gliomas and who had received surgery and adjuvant radiation therapy or salvage radiotherapy as part of their treatment. These patients were followed by the radiation-oncology ward at Shohada-e-Tajrish Hospital in Tehran, Iran, between 2002 and 2012. The log-rank test (univariate) and the Cox proportional hazards model (multivariate) were used to examine the 10-year DFS and OS and to assess the strengths of various histo-clinical factors relative to 10-year DFS and OS. Results: The study included 110 patients for whom 10-year DFS and OS were found to be 23 and 28%, respectively. Favorable prognostic factors in the univariate analysis using the Kaplan-Meier 10-year OS analysis were the following: age below 40, karnofsky performance status (KPS) more than 70, the presence of oligodendroglioma, tumor size of < 5 cm, and gross-total resection (p=0.02, p=0.01, p=0.03, p=0.01, p=0.02, respectively). Good prognostic factors in multivariate analysis using the Cox regression model were as follows: age below 40, the presence of oligodendroglioma, tumor size< 5 cm, and gross total resection in10-year OS (p=0.01, p=0.03, p=0.00, p=0.02, respectively). Conclusions: Gross-total resection, tumor size < 5 cm, age below 40, and the presence of oligodendroglioma had better 10-year DFS and OS rates. We recommend that all patients with LGG tumors be referred to neuro-oncology centers that have sufficient experience to achieve the best results of treatment. PMID:26388977

  2. Innate lymphoid cells and the MHC.

    PubMed

    Robinette, M L; Colonna, M

    2016-01-01

    Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. PMID:26812060

  3. Group 2 innate lymphoid cells in disease.

    PubMed

    Halim, Timotheus Y F

    2016-01-01

    Group 2 innate lymphoid cells (ILC2) are now recognized as an important innate source of type-2 effector cytokines. Although initially associated with mucosal tissues, it is clear that ILC2 are present in diverse anatomical locations. The function of ILC2 at these sites is equally varied, and although ILC2 represent a relatively minor population, they are fundamentally important regulators of innate and adaptive immune processes. As such, there is much interest to understand the role of ILC2 in diseases with a type-2 inflammatory component. This review explores the known roles of ILC2 in disease, and the diseases that show associations or other strong evidence for the involvement of ILC2. PMID:26306498

  4. Thermal Energy Consumption in the Heat-Technology Production of Solid Composite Fuel From Low-Grade Raw Materials

    NASA Astrophysics Data System (ADS)

    Tabakaev, Roman; Astafev, Alexander; Kazakov, Alexander; Zavorin, Alexander

    2016-02-01

    An evaluation is made of the thermal energy consumed in the heat-technology production of solid composite fuel from low-grade organic raw materials. It is shown that the heat of decomposition of the organic mass and the combustion of the by-products of heat-technology may be sufficient to cover all the energy needs for processing peat, brown coal and wood chips. Producing solid composite fuel from sapropel requires external resources to compensate for part of the heat consumed. Calculations show that it is possible for the thermal processing of raw materials to proceed autothermally due to the heat of decomposition when the moisture content at the reactor inlet is limited: for peat it should be no more than 35%, 54% for brown coal, and 37% for wood chips. The low heat of decomposition of the sapropel organic mass means that its thermal processing cannot proceed autothermally.

  5. An inverse problem formulation for parameter estimation of a reaction-diffusion model of low grade gliomas.

    PubMed

    Gholami, Amir; Mang, Andreas; Biros, George

    2016-01-01

    We present a numerical scheme for solving a parameter estimation problem for a model of low-grade glioma growth. Our goal is to estimate the spatial distribution of tumor concentration, as well as the magnitude of anisotropic tumor diffusion. We use a constrained optimization formulation with a reaction-diffusion model that results in a system of nonlinear partial differential equations. In our formulation, we estimate the parameters using partially observed, noisy tumor concentration data at two different time instances, along with white matter fiber directions derived from diffusion tensor imaging. The optimization problem is solved with a Gauss-Newton reduced space algorithm. We present the formulation and outline the numerical algorithms for solving the resulting equations. We test the method using a synthetic dataset and compute the reconstruction error for different noise levels and detection thresholds for monofocal and multifocal test cases. PMID:25963601

  6. Fine-Needle Aspiration Cytology of Low-Grade Cribriform Cystadenocarcinoma with Many Psammoma Bodies of the Salivary Gland

    PubMed Central

    Jeong, Ji Yun; Ahn, Dongbin

    2013-01-01

    Low-grade cribriform cystadenocarcinoma (LGCCC) is a rare salivary gland tumor that was recently defined as a variant of cystadenocarcinoma by the 2005 World Health Orgazniation (WHO) classification system. We report cytologic findings of an unusual case of LGCCC with many psammoma bodies. A 90-year-old man presented a palpable mass on his left parotid gland. Fine-needle aspiration (FNA) cytology showed tumor cells that were arranged in clusters and dispersed individually. The tumor cells showed mild atypia and had clear or dense cytoplasm with some vacuoles. Numerous psammoma bodies were noted. After surgical resection, the histologic examination revealed a mixed solid and cystic mass showing intraductal growth with focal stromal invasion. The S-100 protein expressed in the tumor cells, but smooth muscle actin and p63 were positive only in myoepithelial cells. Although LGCCCs resemble other salivary gland tumors, differentiating LGCCC during preoperative FNA is important to avoid unnecessary overtreatment. PMID:24255638

  7. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

    SciTech Connect

    Jalali, Rakesh; Mallick, Indranil; Dutta, Debnarayan

    2010-07-15

    Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

  8. Long-Term Results of Brachytherapy With Temporary Iodine-125 Seeds in Children With Low-Grade Gliomas

    SciTech Connect

    Korinthenberg, Rudolf; Neuburger, Daniela; Trippel, Michael; Ostertag, Christoph; Nikkhah, Guido

    2011-03-15

    Purpose: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. Methods and Materials: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. Results: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. Conclusions: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

  9. Membrane-Based Osmotic Heat Engine with Organic Solvent for Enhanced Power Generation from Low-Grade Heat

    SciTech Connect

    Shaulsky, E; Boo, C; Lin, SH; Elimelech, M

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher ORE energy efficiency with the LiCl methanol draw solution compared to that with the LiCl water draw solution under practical operating conditions (i.e., heat recovery <90%). We discuss the implications of the results for converting low-grade heat to power.

  10. Membrane-based osmotic heat engine with organic solvent for enhanced power generation from low-grade heat.

    PubMed

    Shaulsky, Evyatar; Boo, Chanhee; Lin, Shihong; Elimelech, Menachem

    2015-05-01

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl-methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl-water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher OHE energy efficiency with the LiCl-methanol draw solution compared to that with the LiCl-water draw solution under practical operating conditions (i.e., heat recovery<90%). We discuss the implications of the results for converting low-grade heat to power. PMID:25839239

  11. Epicardial fat, cardiac dimensions, and low-grade inflammation in young adult monozygotic twins discordant for obesity.

    PubMed

    Granr, Marit; Seppl-Lindroos, Anneli; Rissanen, Aila; Hakkarainen, Antti; Lundbom, Nina; Kaprio, Jaakko; Nieminen, Markku S; Pietilinen, Kirsi H

    2012-05-01

    Epicardial fat with its close proximity to coronary arteries has been suggested to be a significant predictor of cardiovascular disease. We studied the relations among acquired obesity, low-grade inflammation, and genetic factors in the accumulation of epicardial fat. A rare sample (n = 15) of healthy monozygotic (MZ) twin pairs discordant for obesity (intrapair difference in body mass index ?3 kg/m(2)) and 9 concordant MZ pairs 23 to 33 years old were examined for cardiac structure, function, epicardial fat thickness (echocardiography), abdominal subcutaneous tissue, and visceral adipose tissue (VAT), liver fat (magnetic resonance imaging/spectroscopy), and serum high-sensitivity C-reactive protein. In the entire sample, MZ cotwins were remarkably similar in most echocardiographic measurements including epicardial fat (intraclass correlation 0.63, p = 0.0004). However, in the discordant pairs, the obese cotwins (16.5 kg, 23% heavier) had 26% more epicardial fat (p = 0.0029) than nonobese cotwins. They also had significantly larger atrial and left ventricular dimensions. Epicardial fat correlated with VAT (r = 0.49, p = 0.02) in individual twins and when using intrapair differences of measurements within pairs (r = 0.39, p = 0.06). In multiple regression analyses including abdominal subcutaneous tissue, VAT, and liver fat, high-sensitivity C-reactive protein was the only factor that remained significantly associated with epicardial fat in individual twins and within pairs. In conclusion, subjects who share the same genes seem to have similar cardiac dimensions. However, acquired obesity increases epicardial fat independent of genetic factors. The close relation between epicardial fat and low-grade inflammation is likely to contribute to the development of cardiovascular disease in obesity. PMID:22325087

  12. Impact of 14-day bed rest on serum adipokines and low-grade inflammation in younger and older adults.

    PubMed

    Jurdana, Mihaela; Jenko-Pražnikar, Zala; Mohorko, Nina; Petelin, Ana; Jakus, Tadeja; Šimunič, Boštjan; Pišot, Rado

    2015-12-01

    Ageing and inactivity both contribute to systemic inflammation, but the effects of inactivity on inflammation in healthy elderly individuals have not been elucidated. We hypothesised that 14-day bed rest could affect the pro- and anti-inflammatory markers in young subjects differently than in older adults. A short-term 14-day horizontal bed rest study (BR14) has been used as a model of inactivity in two groups of healthy male volunteers: 7 aged 18-30 years (young) and 16 aged 55-65 years (older adults). The effects of inactivity on inflammation were compared. Key low-grade inflammation mediators, tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), visfatin, resistin, and anti-inflammatory adiponectin were measured in fasting serum samples, collected at baseline (BDC) and post BR14. Young responded to BR14 by increasing serum visfatin and resistin while older adults responded to BR14 by increasing IL-6 and TNF-α. In addition, serum adiponectin increased in all participants. Data from correlation analysis demonstrated positive association between Δ serum visfatin and Δ IL-6 in both groups, while Δ serum adiponectin was negatively associated with Δ TNF-α in young and positively associated with Δ resistin in the older adults. As little as 14 days of complete physical inactivity (BR14) negatively affected markers of low-grade inflammation in both groups, but the inflammation after BR14 was more pronounced in older adults. The effect of BR14 on IL-6 and resistin differed between young and older adults. Inflammatory responses to BR14 in older adults differed from those reported in the literature for obese or subjects in pathological states, suggesting potentially different mechanisms between inactivity- and obesity-induced inflammations. PMID:26564239

  13. Long-term survival and functional status of patients with low-grade astrocytoma of spinal cord

    SciTech Connect

    Robinson, Clifford G.; Prayson, Richard A.; Hahn, Joseph F.; Kalfas, Iain H.; Whitfield, Melvin D.; Lee, S.-Y.; Suh, John H. . E-mail: suhj@ccf.org

    2005-09-01

    Purpose: To determine survival and changes in neurologic function and Karnofsky performance status (KPS) in a series of patients treated for low-grade astrocytoma of the spinal cord during the past two decades. Methods: This study consisted of 14 patients with pathologically confirmed low-grade astrocytoma of the spinal cord who were treated between 1980 and 2003. All patients underwent decompressive laminectomy followed by biopsy (n = 7), subtotal resection (n = 6), or gross total resection (n = 1). Ten patients underwent postoperative radiotherapy (median total dose 50 Gy in 28 fractions). The overall survival, progression-free survival, and changes in neurologic function and KPS were measured. Results: The overall survival rate at 5, 10, and 20 years was 100%, 75%, and 60%, respectively. The progression-free survival rate at 5, 10, and 20 years was 93%, 80%, and 60%, respectively. Neither overall survival nor progression-free survival was clearly correlated with any patient, tumor, or treatment factors. Neurologic function and KPS worsened after surgery in 8 (57%) of 14 and 9 (69%) of 13 patients, respectively. At a mean follow-up of 10.2 years, neurologic function had stabilized or improved in 8 (73%) of 11 remaining patients, but the KPS had worsened in 5 (50%) of 10. Most patients who were employed before surgery were working at last follow-up. Conclusion: Patients who undergo gross total resection of their tumor may be followed closely. Patients who undergo limited resection should continue to receive postoperative RT (50.4 Gy in 1.8-Gy fractions). The functional measures should be routinely evaluated to appreciate the treatment outcomes.

  14. Dynamics of HIV infection in lymphoid tissue network.

    PubMed

    Nakaoka, Shinji; Iwami, Shingo; Sato, Kei

    2016-03-01

    Human immunodeficiency virus (HIV) is a fast replicating ribonucleic acid virus, which can easily mutate in order to escape the effects of drug administration. Hence, understanding the basic mechanisms underlying HIV persistence in the body is essential in the development of new therapies that could eradicate HIV infection. Lymphoid tissues are the primary sites of HIV infection. Despite the recent progress in real-time monitoring technology, HIV infection dynamics in a whole body is unknown. Mathematical modeling and simulations provide speculations on global behavior of HIV infection in the lymphatic system. We propose a new mathematical model that describes the spread of HIV infection throughout the lymphoid tissue network. In order to represent the volume difference between lymphoid tissues, we propose the proportionality of several kinetic parameters to the lymphoid tissues' volume distribution. Under this assumption, we perform extensive numerical computations in order to simulate the spread of HIV infection in the lymphoid tissue network. Numerical computations simulate single drug treatments of an HIV infection. One of the important biological speculations derived from this study is a drug saturation effect generated by lymphoid network connection. This implies that a portion of reservoir lymphoid tissues to which drug is not sufficiently delivered would inhibit HIV eradication despite of extensive drug injection. PMID:26507442

  15. Benign Lymphoid Hyperplasia Presenting as Bilateral Scleral Nodules

    PubMed Central

    Cumba, Ricardo J.; Vazquez-Botet, Rene

    2015-01-01

    Purpose. To report a case of transient lymphoid hyperplasia presenting as bilateral nodular scleral mass in a young male patient. Design. Observational case report. Methods. Chart review. Causes of scleritis were considered and excluded based on detailed history, physical examination, and laboratory investigations. Results. Excisional biopsy of scleral lesions indicated lymphoid tissue. Immunohistochemical studies revealed a polyclonal population of T and B cells consistent with a benign reactive process. Conclusions. Chronic exposure of the ocular adnexa to many allergens and irritants may lead to activation of the inflammatory cascade. In severely allergic patients activation may be exponential and elicit an immune-mediated response resulting in a transient lymphoid reactive process. PMID:26421203

  16. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease

    PubMed Central

    2011-01-01

    Background The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. Results Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. Conclusions These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity. PMID:21219646

  17. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    PubMed

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7R?(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (?63%) and aryl hydrocarbon receptor and produced IL-17 (?63%), IL-22 (?36%), and TNF-? (?72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.-Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques. PMID:26283536

  18. Long-term treatment of residual or recurrent low-grade endometrial stromal sarcoma with aromatase inhibitors: A report of two cases and a review of the literature

    PubMed Central

    RYU, HYEWON; CHOI, YOON-SEOK; SONG, IK-CHAN; YUN, HWAN-JUNG; JO, DEOG-YEON; KIM, SAMYONG; LEE, HYO JIN

    2015-01-01

    Endometrial stromal sarcoma (ESS) occurs rarely and accounts for only 0.2% of all uterine malignancies. ESS usually expresses estrogen and progesterone receptors, and is regarded as hormone-sensitive. Due to the rarity of these tumors, there are only few case series on the use of aromatase inhibitors in the treatment of low-grade ESS. The present study reports the cases of two patients with residual or recurrent low-grade ESS who experienced long-term disease-free survival following treatment with letrozole. The study also reviews the literature with regard to the data on aromatase inhibitors used in patients with low-grade ESS. In total, 30 patients with recurrent or residual low-grade ESS who were treated with aromatase inhibitors were identified, including the present cases. Among the 30 patients, the overall response rate of advanced low-grade ESS to aromatase inhibitors was 77.4% (complete response, 25.8%; partial response, 51.6%) and the disease control rate was 90.3%. The response rate of first-line treatment was similar to that of second-line therapy or higher (84.6 vs. 72.2%; P=0.453). Duration of aromatase inhibitor treatment ranged from 1.5 to 168 months (median, 26.5 months). The aromatase inhibitors showed minimal adverse effects. In conclusion, aromatase inhibitors, particularly third-generation drugs, are a well-tolerated class of medications that are effective in the treatment of advanced low-grade ESS, with a favorable toxicity profile. PMID:26722331

  19. Secondary Lymphoid Organs: Responding to Genetic and Environmental Cues in Ontogeny and the Immune Response1

    PubMed Central

    Ruddle, Nancy H.; Akirav, Eitan M.

    2009-01-01

    Secondary lymphoid organs (SLOs) include lymph nodes (LNs), spleen, Peyer’s patches (PPs) and mucosal tissues- the nasal associated lymphoid tissue (NALT), adenoids, and tonsils. Less discretely anatomically defined cellular accumulations include the bronchus associated lymphoid tissue (BALT), cryptopatches, and isolated lymphoid follicles (ILFs). All SLOs serve to generate immune responses and tolerance. SLO development depends on the precisely regulated expression of cooperating lymphoid chemokines and cytokines LTα, LTβ, RANKL, TNF, IL-7, and perhaps IL-17. The relative importance of these factors varies between the individual lymphoid organs. Participating in the process are lymphoid tissue initiator (ltin), lymphoid tissue inducer (ltind), and lymphoid tissue organizer (lto) cells. These cells, and others that produce the crucial cytokines, maintain SLOs in the adult. Similar signals regulate the transition from inflammation to ectopic or tertiary lymphoid tissues (TLOs). PMID:19661265

  20. Organic Fluids and Passive Cooling in a Supercritical Rankine Cycle for Power Generation from Low Grade Heat Sources

    NASA Astrophysics Data System (ADS)

    Vidhi, Rachana

    Low grade heat sources have a large amount of thermal energy content. Due to low temperature, the conventional power generation technologies result in lower efficiency and hence cannot be used. In order to efficiently generate power, alternate methods need to be used. In this study, a supercritical organic Rankine cycle was used for heat source temperatures varying from 125C to 200C. Organic refrigerants with zero ozone depletion potential and their mixtures were selected as working fluid for this study while the cooling water temperature was changed from 10-25C. Operating pressure of the cycle has been optimized for each fluid at every heat source temperature to obtain the highest thermal efficiency. Energy and exergy efficiencies of the thermodynamic cycle have been obtained as a function of heat source temperature. Efficiency of a thermodynamic cycle depends significantly on the sink temperature. At areas where water cooling is not available and ambient air temperature is high, efficient power generation from low grade heat sources may be a challenge. Use of passive cooling systems coupled with the condenser was studied, so that lower sink temperatures could be obtained. Underground tunnels, buried at a depth of few meters, were used as earth-air-heat-exchanger (EAHE) through which hot ambient air was passed. It was observed that the air temperature could be lowered by 5-10C in the EAHE. Vertical pipes were used to lower the temperature of water by 5C by passing it underground. Nocturnal cooling of stored water has been studied that can be used to cool the working fluid in the thermodynamic cycle. It was observed that the water temperature can be lowered by 10-20C during the night when it is allowed to cool. The amount of water lost was calculated and was found to be approximately 0.1% over 10 days. The different passive cooling systems were studied separately and their effects on the efficiency of the thermodynamic cycle were investigated. They were then combined into a novel condenser design that uses passive cooling technology to cool the working fluid that was selected in the first part of the study. It was observed that the efficiency of the cycle improved by 2-2.5% when passive cooling system was used.

  1. Innate lymphoid cells, possible interaction with microbiota.

    PubMed

    Moro, Kazuyo; Koyasu, Shigeo

    2015-01-01

    Recent studies have identified novel lymphocyte subsets named innate lymphoid cells (ILCs) lacking antigen-specific receptors. ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells. ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively. ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers. Excessive activation of ILCs, however, leads to various inflammatory disease conditions. ILCs have thus attracted interests of many researchers in the fields of infectious immunity, inflammatory diseases, and allergic diseases. Because epithelial cells sense alterations in environmental cues, it is important to understand the functional interaction between epithelial cells, ILCs, and environmental factors such as commensal microbiota. We discuss in this review developmental pathways of ILCs, their functions, and contribution of commensal microbiota to the differentiation and function of ILCs. PMID:25502370

  2. Changes in Primary Lymphoid Organs With Aging

    PubMed Central

    Chinn, Ivan K.; Blackburn, Clare C.; Manley, Nancy R.; Sempowski, Gregory D.

    2012-01-01

    Aging is associated with decreased immune function that leads to increased morbidity and mortality in the elderly. Immune senescence is accompanied by age-related changes in two primary lymphoid organs, bone marrow and thymus, that result in decreased production and function of B and T lymphocytes. In bone marrow, hematopoietic stem cells exhibit reduced self-renewal potential, increased skewing toward myelopoiesis, and decreased production of lymphocytes with aging. These functional sequelae of aging are caused in part by increased oxidative stress, inflammation, adipocyte differentiation, and disruption of hypoxic osteoblastic niches. In thymus, aging is associated with tissue involution, exhibited by a disorganization of the thymic epithelial cell architecture and increased adiposity. This dysregulation correlates with a loss of stroma-thymocyte ‘cross-talk’, resulting in decreased export of naïve T cells. Mounting evidence argues that with aging, thymic inflammation, systemic stress, local Foxn1 and keratinocyte growth factor expression, and sex steroid levels play critical roles in actively driving thymic involution and overall adaptive immune senescence across the lifespan. With a better understanding of the complex mechanisms and pathways that mediate bone marrow and thymus involution with aging, potential increases for the development of safe and effective interventions to prevent or restore loss of immune function with aging. PMID:22559987

  3. Humanized hemato-lymphoid system mice

    PubMed Central

    Theocharides, Alexandre P.A.; Rongvaux, Anthony; Fritsch, Kristin; Flavell, Richard A.; Manz, Markus G.

    2016-01-01

    Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. PMID:26721800

  4. Humanized hemato-lymphoid system mice.

    PubMed

    Theocharides, Alexandre P A; Rongvaux, Anthony; Fritsch, Kristin; Flavell, Richard A; Manz, Markus G

    2016-01-01

    Over the last decades, incrementally improved xenograft mouse models, supporting the engraftment and development of a human hemato-lymphoid system, have been developed and now represent an important research tool in the field. The most significant contributions made by means of humanized mice are the identification of normal and leukemic hematopoietic stem cells, the characterization of the human hematopoietic hierarchy, and their use as preclinical therapy models for malignant hematopoietic disorders. Successful xenotransplantation depends on three major factors: tolerance by the mouse host, correct spatial location, and appropriately cross-reactive support and interaction factors such as cytokines and major histocompatibility complex molecules. Each of these can be modified. Experimental approaches include the genetic modification of mice to faithfully express human support factors as non-cross-reactive cytokines, to create free niche space, the co-transplantation of human mesenchymal stem cells, the implantation of humanized ossicles or other stroma, and the implantation of human thymic tissue. Besides the source of hematopoietic cells, the conditioning regimen and the route of transplantation also significantly affect human hematopoietic development in vivo. We review here the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. PMID:26721800

  5. Papillary Immature Metaplasia of the Anal Canal: A Low-grade Lesion That Can Mimic a High-grade Lesion.

    PubMed

    Roberts, Jennifer M; Cornall, Alyssa M; Ekman, Deborah; Law, Carmella; Poynten, I Mary; Jin, Fengyi; Hillman, Richard J; Templeton, David J; Tabrizi, Sepehr N; Garland, Suzanne M; Thurloe, Julia K; Grulich, Andrew E; Farnsworth, Annabelle

    2016-03-01

    In a natural history study of anal human papillomavirus (HPV) infection and HPV-related lesions among homosexual men in Sydney, Australia, we identified 15 examples of papillary immature metaplasia (PIM) in anal biopsy samples. PIM has previously been described in the cervix, but not in the anal canal. PIM is a form of exophytic low-grade squamous intraepithelial lesion (eLSIL) also known as condyloma. In contrast to the maturing keratinocytes and koilocytosis seen in conventional eLSIL, the slender papillary structures of PIM have a surface population of immature squamous cells. In our anal samples PIM was characterized by close proximity to conventional eLSIL, was negative for p16 (p16) expression, and revealed the presence of a single low-risk HPV genotype (either 6 or 11) in laser capture microdissected lesions. The clinical significance of recognizing PIM lies in preventing misdiagnosis as high-grade squamous intraepithelial lesion, (the presumed precursor to anal cancer), due to the morphologic immaturity of the cell population. In routine practice, awareness of anal canal PIM and p16 immunostaining will prevent this. Further study of the natural history of anal canal PIM is needed. PMID:26551619

  6. An Efficient Technology for Smelting Low Grade Bismuth-Lead Concentrate: Oxygen-Rich Side Blow Process

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Hao, Zhandong; Yang, Tianzu; Xiao, Hui; Liu, Weifeng; Zhang, Duchao; Bin, Shu; Bin, Wanda

    2015-09-01

    An efficient technology for low-grade bismuth-lead concentrate smelting is reported. In the process, two oxygen-rich side blow furnaces (OSBF) are used for oxidative smelting of the concentrate and reductive smelting of the oxidized slag from the upstream furnace, respectively. Slags are collected from the OSBFs by certain intervals during an operation period and analyzed by inductively coupled plasma-atomic emission spectrum, x-ray diffraction and scanning electron microscopy. Analysis for the oxidized slag revealed that spherical or oval metallic inclusions with sizes range from submicron to 40 ?m in diameter are randomly embedded in the glassy matrix. On the one hand, the metal content of the inclusions is close to that of the bottom metal alloy, indicating metal inclusions are physically entrained in the oxidized slag. On the other hand, metal inclusions are not identified in the reduced slag, disclosing the strong metal-slag separation ability of the OSBF. The bismuth content of the reduced slag is about 0.05 wt.%, which is 6-10 times lower than that of the traditional pyrometallurgical processes.

  7. Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications.

    PubMed

    Pérez-García, Víctor M; Bogdanska, Magdalena; Martínez-González, Alicia; Belmonte-Beitia, Juan; Schucht, Philippe; Pérez-Romasanta, Luis A

    2015-09-01

    Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment. PMID:24860116

  8. Cortical and Standard Trajectory Pedicle Screw Fixation Techniques in Stabilizing Multisegment Lumbar Spine with Low Grade Spondylolisthesis

    PubMed Central

    ?nceo?lu, Serkan

    2015-01-01

    Background Cortical screw (CS) fixation has been recently proposed as an alternative to the standard pedicle screw (PS) fixation technique. Biomechanical studies involving individual screw pullout and single level motion segment stabilization showed comparable performance of both techniques. However, whether this new fixation technique can be applied to the stabilization of multilevel lumbar segments with significant destabilization has been unclear. Purpose To compare stability of CS fixation to the traditional PS fixation in an unstable 3 level spondylolisthesis model. Study Design This is a biomechanical study comparing cortical trajectory pedicle screw fixation to traditional trajectory pedicle screw fixation in an unstable cadaveric model using nondestructive flexibility test. Methods Eight fresh frozen cadaveric lumbar spines (T12- S1) were obtained. After intact baseline testing, a 3-level lowgrade spondylolisthesis was simulated at the L1-4. Each specimen was instrumented with the PS and CS fixation systems. Standard nondestructive flexibility test was performed. Range of motion at each level was compared between the constructs during flexion-extension, lateral bending, and axial rotation. Results The destabilization model significantly increased the ROM in all planes (P<0.05). Both fixation techniques provided significant reduction in the ROM (P<0.05). There was no significant difference in ROM between the PS and CS groups in any of planes (P>0.05). Conclusions Cortical trajectory pedicle screw fixation provided stabilization to multilevel lumbar segment with low-grade spondylolisthesis comparable to the standard trajectory pedicle screw construct. PMID:26484009

  9. Low-grade quarry products, reclaimed aggregates and inert wastes -- their use in unbound mixtures for road pavements

    SciTech Connect

    Rockliff, D.

    1996-12-31

    The UK Specification for Highway Works appears to encourage the use of low-grade quarry products and a range of reclaimed aggregates and inert wastes in earthworks. However, in practice, materials used in earthworks are judged against requirements designed to assess the compatibility of soils. Compliance with compactibility criteria rather than fit for purpose criteria can lead to the use of higher quality aggregates than is strictly necessary. For many years UK clients have had supplies of good quality granular subbase material available at low cost. The use of such aggregates in non-structural fill layers presents few risks, but diverts the aggregate from more appropriate end uses, such as asphalts. Proponents of the greater use of wastes and reclaimed aggregates face the same dilemma. The development of European (CEN) Standards may influence the situation. These Standards are designed to ensure that barriers to trade are removed for products placed on the market. The new Standards aim to be blind to the source of the material and to reflect the wide range of national practices across Europe. The CEN work may give a status to a number of tests that are more appropriate to the control of unbound mixtures than those currently used in the UK.

  10. Volumes and growth rates of untreated adult low-grade gliomas indicate risk of early malignant transformation.

    PubMed

    Rees, Jeremy; Watt, Hilary; Jger, H Rolf; Benton, Chris; Tozer, Daniel; Tofts, Paul; Waldman, Adam

    2009-10-01

    Adult low-grade gliomas (LGG) grow slowly, but most eventually undergo malignant transformation. The relationship between tumour volume, growth rate and the likelihood of transformation is unknown. Twenty-seven patients with biopsy-proven, untreated LGG had at least three MRI studies at 6 monthly intervals. Tumour volumes and growth rates were calculated using semi-automated segmentation, and analysed in a hierarchical regression model. In a 3-year period, patients who showed clinical deterioration and/or new (or significantly increased) contrast enhancement were classified as transformers (T), whilst non-transformers (NT) remained stable clinically and by conventional radiological criteria. All LGG showed progressive growth. Volumes at study entry were smaller in 9NT (57 ml, 95% CI 35-80 ml) than in 18T (83 ml, 95% CI 70-96 ml) (p=0.03). Average annual growth rates were lower in NT (16% (95% CI 9-23%)) than in T (26% (95% CI 20-31%)) (p=0.046), until the penultimate study. Growth in T increased to 56% p.a. (95% CI 20-92%) in the 6 months prior to transformation. In T, tumour volume was the most significant predictor of transformation in the following 12 months. Sequential measurement of LGG volume allows accurate determination of growth rates and identification of patients whose tumours are at high risk of early transformation. PMID:18632238

  11. A Case of Metastatic Low-Grade Endometrial Stromal Sarcoma Treated with Letrozole after Ovarian Ablation by Radiotherapy.

    PubMed

    Yang, Kyung Ho; Shin, Jung A; Jung, Joo Hyuk; Jung, Hae Won; Lee, Hye Ran; Chang, Sunhee; Park, Ji Yeon; Yi, Seong Yoon

    2015-10-01

    A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient's levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy. PMID:25715770

  12. Pollution control and metal resource recovery for low grade automobile shredder residue: a mechanism, bioavailability and risk assessment.

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-04-01

    Automobile shredder residue (ASR) is considered as hazardous waste in Japan and European countries due to presence of heavy metals. This study was carried on the extraction characteristics of heavy metals (Mn, Fe, Ni, and Cr) from automobile shredder residue (ASR). The effects of pH, temperature, particle size, and liquid/solid ratio (L/S) on the extraction of heavy metals were investigated. The recovery rate of Mn, Fe, Ni, and Cr increased with increasing extraction temperature and L/S ratio. The lowest pH 2, the highest L/S ratio, and the smallest particle size showed the highest recovery of heavy metals from ASR. The highest recovery rates were in the following order: Mn > Ni > Cr > Fe. Reduction of mobility factor for the heavy metals was observed in all the size fractions after the recovery. The results of the kinetic analysis for various experimental conditions supported that the reaction rate of the recovery process followed a second order reaction model (R(2) ⩾ 0.95). The high availability of water-soluble fractions of Mn, Fe, Ni, and Cr from the low grade ASR could be potential hazards to the environment. Bioavailability and toxicity risk of heavy metals reduced significantly with pH 2 of distilled water. However, water is a cost-effective extracting agent for the recovery of heavy metals and it could be useful for reducing the toxicity of ASR. PMID:25690411

  13. Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy.

    PubMed

    Dodgshun, Andrew J; Maixner, Wirginia J; Heath, John A; Sullivan, Michael J; Hansford, Jordan R

    2016-01-15

    Pediatric low-grade gliomas (LGG) that are unresectable often require adjuvant chemotherapy such as carboplatin/vincristine. Small Phase II studies have suggested equivalent efficacy of single agent 4-weekly carboplatin. A single-institution retrospective review captured all patients aged 0 to 18 years diagnosed with LGG between 1996 and 2013 and treated with carboplatin monotherapy. The response and survival according to tumor site was compared to published results for multiagent chemotherapy. Of 268 children diagnosed with LGG diagnosed in this period, 117 received chemotherapy and 104 children received single agent carboplatin as first line chemotherapy. All patients received carboplatin at 560 mg/m(2) , four-weekly for a median of 12 courses. The mean age at diagnosis was 5.8 years (range 3m-16y) and 32% had neurofibromatosis type 1. With a mean followup of 54 months, 86% of patients achieved stabilisation or better (SD/PR/CR). 3-year progression free survival (PFS) 66% (95% CI 57-76%), and 5-year PFS was 51% (95% CI 41-63%). 5-year overall survival was 97%. Multivariate analysis showed poorer PFS for those with chiasmatic/hypothalamic tumors. In this retrospective analysis single agent carboplatin shows comparable efficacy to historical multiagent chemotherapy for the treatment of patients with unresectable LGG. Equivalent outcomes are achieved with less chemotherapy, reduced side effects and fewer hospital visits. Further research is required to establish the place of this simplified regimen in the up-front treatment of unresectable LGG. PMID:26235348

  14. Calorimetry of the PD-D{sub 2}O system: The drive towards high levels of low grade heat

    SciTech Connect

    Fleischmann, M.; Pons, S.

    1995-12-01

    We review some of the factors which prompted our search for anomalously fast nuclear reactions of D{sup +} electrochemically compressed into Pd (and Pd-alloy) host lattices using calorimetry as a principal means of investigation. The most surprising results are that the high levels of excess heat generated are riot accompanied by the expected levels of tritium and neutrons (low but significant levels of these {open_quotes}nuclear ashes{close_quotes} are detected). It has been found that excess heat generation is dependent on the protocol of the experiments mainly because of positive feedback. A rationale for such positive feedback is presented; this also leads to oscillation in the system properties which must be minimised so as to reach high levels of excess enthalpy generation at intermediate temperatures ({approximately}100{degrees}C i.e. low grade heat). We illustrate the progressive development by the achievement of specific rates of {approximately}20Wcm{sup -3}, {approximately}100Wcm{sup -3} and 4kWcm{sup -3} corresponding to those of gas cooled, pressurised water and fast breeder reactors. The highest levels require restrictions of the engineering of the systems which we will outline.

  15. EWSR1-CREB3L1 gene fusion: a novel alternative molecular aberration of low-grade fibromyxoid sarcoma.

    PubMed

    Lau, Patrick P L; Lui, Philip C W; Lau, Gene T C; Yau, Derek T W; Cheung, Elaine T Y; Chan, John K C

    2013-05-01

    Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon sarcoma with a deceptively bland-looking morphology that disguises its malignant clinical behavior. It shows distinctive chromosomal translocations resulting in fusion of FUS with the CREB3L2 gene in most cases and CREB3L1 in rare cases. Thus molecular studies are particularly helpful in the diagnosis of this bland-looking sarcoma. We report 2 cases of LGFMS serendipitously found to harbor a novel alternative EWSR1-CREB3L1 gene fusion, as confirmed by DNA sequencing of reverse transcriptase-polymerase chain reaction products and fluorescence in situ hybridization. One patient was a child who presented with a subcutaneous nodule on the lower leg, and the other was a middle-aged woman who had a mass lesion over the proximal thigh. Morphologically, one case showed a spindle cell tumor with hyalinization and giant rosettes, whereas the other showed classical histology of LGFMS with focal metaplastic bone formation. Immunostaining for MUC4 showed extensive positive staining. Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma. PMID:23588368

  16. Comparative analytical determination of thorium in medium and low-grade minerals and ores using Semimethylthymol Blue

    SciTech Connect

    Hafez, M.A.H.; Kenawy, I.M.M.; Ramadan, M.A.M.

    1994-05-01

    The composition, stability constants and molar absorption coefficient of the chelate of thorium ion with Semimethylthymol Blue, SMTB is determined spectrophotometrically in a medium of perchloric acid and sodium perchlorate solution (pH 2.0). In the thorium-SMTB system, a purple red Th(SMTB) chelate is formed with logarithmic overall stability constant of 20.76{+-}0.01 and molar absorption coefficient of 1.44{times}10{sup 4} (560 nm) dm{sup 3} mol{sup {minus}1} cm{sup {minus}1}. SMTB was proposed as a new reagent for the spectrophotometric determination of micro-molar amounts of thorium at {lambda}{sub max} 560 nm. The colour development depends on time, temperature, pH and buffer species. The interferences of different anions, cations and organic acids on thorium determination were also investigated. Beer`s law was obeyed for 11.6-104.4 {mu}g Th(IV)/25 ml(0.46-4.18 ppm). SMTB was used for the spectrophotometric determination of thorium in medium and low-grade minerals and ores and the results were reproducible and satisfactory. Comparative study including different statistical tests between the spectrophotometric and complexometric determinations of thorium in its minerals and ores using SMTB has been carried out.

  17. How Commonly Is the Diagnosis of Gastric Low Grade Dysplasia Upgraded following Endoscopic Resection? A Meta-Analysis.

    PubMed

    Zhao, Guangfeng; Xue, Meng; Hu, Yingying; Lai, Sanchuan; Chen, Shujie; Wang, Liangjing

    2015-01-01

    Gastric dysplasia is a well-known precancerous lesion. Though the diagnosis of gastric low grade dysplasia (LGD) is generally made from endoscopic forceps biopsy (EFB), the accuracy is doubtful after numerous EFB-proven gastric LGD were upgraded to gastric high grade dysplasia (HGD) or even carcinoma (CA) by further diagnostic test with the procedure of endoscopic resection (ER). We aimed to evaluate the upgraded diagnosis rate (UDR) and the risk factors by ER in EFB-proven gastric LGD lesions. Two investigators independently searched studies reporting the UDR by ER in EFB-proven gastric LGD lesions from databases and analyzed the overall UDR, HGD-UDR and CA-UDR. The pooled UDR by ER in EFB-proven gastric LGD lesions was 25.0% (95% CI, 20.2%-29.8%), made up of HGD-UDR and CA-UDR by rates of 16.7% (95% CI, 12.8%-20.6%) and 6.9% (95% CI, 4.2%-9.6%) respectively. Lesion size larger than 2 cm, surface with depression and nodularity under endoscopic examinations were the major risk factors associated with UDR. In conclusion, one quarter of EFB-proven gastric LGD lesions will be diagnosed as advanced lesions, including gastric HGD (16.7%) and gastric CA (6.9%) by ER. The diagnosis of those LGD lesions with an endoscopic diameter larger than 2cm, and depressed or nodular surface are more likely to be upgraded after ER. PMID:26182344

  18. How Commonly Is the Diagnosis of Gastric Low Grade Dysplasia Upgraded following Endoscopic Resection? A Meta-Analysis

    PubMed Central

    Zhao, Guangfeng; Xue, Meng; Hu, Yingying; Lai, Sanchuan; Chen, Shujie; Wang, Liangjing

    2015-01-01

    Gastric dysplasia is a well-known precancerous lesion. Though the diagnosis of gastric low grade dysplasia (LGD) is generally made from endoscopic forceps biopsy (EFB), the accuracy is doubtful after numerous EFB-proven gastric LGD were upgraded to gastric high grade dysplasia (HGD) or even carcinoma (CA) by further diagnostic test with the procedure of endoscopic resection (ER). We aimed to evaluate the upgraded diagnosis rate (UDR) and the risk factors by ER in EFB-proven gastric LGD lesions. Two investigators independently searched studies reporting the UDR by ER in EFB-proven gastric LGD lesions from databases and analyzed the overall UDR, HGD-UDR and CA-UDR. The pooled UDR by ER in EFB-proven gastric LGD lesions was 25.0% (95% CI, 20.2%-29.8%), made up of HGD-UDR and CA-UDR by rates of 16.7% (95% CI, 12.8%-20.6%) and 6.9% (95% CI, 4.2%-9.6%) respectively. Lesion size larger than 2 cm, surface with depression and nodularity under endoscopic examinations were the major risk factors associated with UDR. In conclusion, one quarter of EFB-proven gastric LGD lesions will be diagnosed as advanced lesions, including gastric HGD (16.7%) and gastric CA (6.9%) by ER. The diagnosis of those LGD lesions with an endoscopic diameter larger than 2cm, and depressed or nodular surface are more likely to be upgraded after ER. PMID:26182344

  19. Low-Grade Fibromyxoid Sarcoma: Incidence, Treatment Strategy of Metastases, and Clinical Significance of the FUS Gene.

    PubMed

    Maretty-Nielsen, Katja; Baerentzen, Steen; Keller, Johnny; Dyrop, Heidi Buvarp; Safwat, Akmal

    2013-01-01

    Aim. The aim of this study was to assess the incidence of low-grade fibromyxoid sarcoma (LGFMS), present treatment results of metastatic LGFMS, and investigate the clinical significance of the FUS gene rearrangement. Methods. This study included 14 consecutive LGFMS patients treated at the Aarhus Sarcoma Centre in 1979-2010. Fluorescent in situ hybridization (FISH) analysis for FUS break-apart was performed for all patients. Results. The incidence of LGFMS was 0.18 per million, representing 0.6% of all soft tissue sarcomas. Four patients needed multiple biopsies/resections before the correct diagnosis was made. Four patients experienced local recurrence, and three patients developed metastases. The treatment of metastatic LGFMS varied from multiagent chemotherapy to repeated, selective surgery of operable metastases. The best response to chemotherapy was short-term stabilization of disease progression, seen with Trabectedin. The prevalence of the FUS break-apart was 21.4%. We found no significant difference in clinical characteristics and outcomes in correlation with the FUS break-apart. Conclusion. LGFMS is a rare disease with multiple challenges. The FUS break-apart was not associated with local recurrence or metastases in our study. To date the only treatment resulting in disease-free periods is surgery; however further investigation into the management of metastatic LGFMS is necessary. PMID:23818812

  20. Cellular automata (CA) simulation of the interaction of vehicle flows and pedestrian crossings on urban low-grade uncontrolled roads

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Wang, Yan

    2015-08-01

    This paper discusses the interaction of vehicle flows and pedestrian crossings on uncontrolled low-grade roads or branch roads without separating barriers in cities where pedestrians may cross randomly from any location on both sides of the road. The rules governing pedestrian street crossings are analyzed, and a cellular automata (CA) model to simulate the interaction of vehicle flows and pedestrian crossings is proposed. The influence of the interaction of vehicle flows and pedestrian crossings on the volume and travel time of the vehicle flow and the average wait time for pedestrians to cross is investigated through simulations. The main results of the simulation are as follows: (1) The vehicle flow volume decreases because of interruption from pedestrian crossings, but a small number of pedestrian crossings do not cause a significant delay to vehicles. (2) If there are many pedestrian crossings, slow vehicles will have little chance to accelerate, causing travel time to increase and the vehicle flow volume to decrease. (3) The average wait time for pedestrians to cross generally decreases with a decrease in vehicle flow volume and also decreases with an increase in the number of pedestrian crossings. (4) Temporal and spatial characteristics of vehicle flows and pedestrian flows and some interesting phenomena such as "crossing belt" and "vehicle belt" are found through the simulations.

  1. Current Understanding of BRAF Alterations in Diagnosis, Prognosis, and Therapeutic Targeting in Pediatric Low-Grade Gliomas

    PubMed Central

    Penman, Catherine Louise; Faulkner, Claire; Lowis, Stephen P.; Kurian, Kathreena M.

    2015-01-01

    The mitogen-activated protein kinase (MAPK) pathway is known to play a key role in the initiation and maintenance of many tumors as well as normal development. This often occurs through mutation of the genes encoding RAS and RAF proteins which are involved in signal transduction in this pathway. BRAF is one of three RAF kinases which act as downstream effectors of growth factor signaling leading to cell cycle progression, proliferation, and survival. Initially reported as a point mutation (V600E) in the majority of metastatic melanomas, other alterations in the BRAF gene have now been reported in a variety of human cancers including papillary thyroid cancer, colon carcinomas, hairy cell leukemia, and more recently in gliomas. The identification of oncogenic mutations in the BRAF gene have led to a revolution in the treatment of metastatic melanoma using targeted molecular therapies that affect the MAPK pathway either directly through BRAF inhibition or downstream through inhibition of MEK. This review describes the molecular biology of BRAF in the context of pediatric low-grade gliomas, the role of BRAF as a diagnostic marker, the prognostic implications of BRAF, and evidence for therapeutic targeting of BRAF. PMID:25785246

  2. A Comparison of Brain Wave Patterns of High and Low Grade Point Average Students During Rest, Problem Solving, and Stress Situations.

    ERIC Educational Resources Information Center

    Montor, Karel

    The purpose of this study was to compare brain wave patterns produced by high and low grade point average students, while they were resting, solving problems, and subjected to stress situations. The study involved senior midshipmen at the United States Naval Academy. The high group was comprised of those whose cumulative grade point average was…

  3. Total lymphoid irradiation for multiple sclerosis

    SciTech Connect

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.

  4. Biology of germinal centers in lymphoid tissue.

    PubMed

    Thorbecke, G J; Amin, A R; Tsiagbe, V K

    1994-08-01

    Germinal centers in lymphoid tissue are the sites of generation of memory B cells undergoing isotype switching and somatic mutation in their Ig genes. Their formation cannot be induced by stimuli other than immunogenic ones. It seems likely that in the function and possibly also in the formation of germinal centers, one important factor is the localization of immune complexes with fixed complement on the surface of follicular dendritic cells. CD4+ T cells, located primarily in the "apical light zones" of the centers, are necessary for germinal center formation. However, their exact role in the process needs clarification, as both cell to cell contact and cytokine production could be involved at different stages of the germinal center generation. These T cells are usually specific for the antigen inducing the germinal center, but they may sometimes respond to other surface components on the B cell surface. In view of the possible stimulatory role of CD4+ T cells in follicular center-derived lymphomas, the functional significance of these T cells in germinal center proliferation is important to unravel. The B cells in germinal centers proliferate extremely rapidly, especially those located in the "dark zones." Many of them undergo apoptosis, particularly in the "basal light zones." The microenvironment of these centers is well suited to the task of expanding and selecting memory B cells of high affinity for the inducing antigen. The interactions of the proliferating B cells with dendritic cells and T cells, unevenly distributed in the various zones of the germinal center, are thought to determine which cells deserve rescue from apoptosis and induction to differentiation into small resting memory B cells. The memory B cells that emerge from the germinal center bear sIg, usually of "switched" isotype, and exhibit somatic mutations in the variable regions of their rearranged Ig genes. PMID:8070632

  5. Inhibition of autophagy overcomes glucocorticoid resistance in lymphoid malignant cells

    PubMed Central

    Jiang, Lei; Xu, Lingzhi; Xie, Jiajun; Li, Sisi; Guan, Yanchun; Zhang, Yan; Hou, Zhijie; Guo, Tao; Shu, Xin; Wang, Chang; Fan, Wenjun; Si, Yang; Yang, Ya; Kang, Zhijie; Fang, Meiyun; Liu, Quentin

    2015-01-01

    Glucocorticoid (GC) resistance remains a major obstacle to successful treatment of lymphoid malignancies. Till now, the precise mechanism of GC resistance remains unclear. In the present study, dexamethasone (Dex) inhibited cell proliferation, arrested cell cycle in G0/G1-phase, and induced apoptosis in Dex-sensitive acute lymphoblastic leukemia cells. However, Dex failed to cause cell death in Dex-resistant lymphoid malignant cells. Intriguingly, we found that autophagy was induced by Dex in resistant cells, as indicated by autophagosomes formation, LC3-I to LC3-II conversion, p62 degradation, and formation of acidic autophagic vacuoles. Moreover, the results showed that Dex reduced the activity of mTOR pathway, as determined by decreased phosphorylation levels of mTOR, Akt, P70S6K and 4E-BP1 in resistant cells. Inhibition of autophagy by either chloroquine (CQ) or 3-methyladenine (3-MA) overcame Dex-resistance in lymphoid malignant cells by increasing apoptotic cell death in vitro. Consistently, inhibition of autophagy by stably knockdown of Beclin1 sensitized Dex-resistant lymphoid malignant cells to induction of apoptosis in vivo. Thus, inhibition of autophagy has the potential to improve lymphoid malignancy treatment by overcoming GC resistance. PMID:25778879

  6. Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

    SciTech Connect

    Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

    2014-05-15

    Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

  7. Surface Papillary Epithelial Hyperplasia (Rough Mucosa) is a Helpful Clue for Identification of Polymorphous Low-Grade Adenocarcinoma.

    PubMed

    Chi, Angela C; Neville, Brad W

    2015-06-01

    The purpose of this study is to evaluate surface papillary epithelial hyperplasia, a microscopic finding that corresponds to the clinical finding of rough or stippled mucosa, as a predictor of polymorphous low-grade adenocarcinoma (PLGA). We conducted a retrospective review of minor salivary gland neoplasms submitted to our biopsy service from 1991 to 2013. Our review was limited to lesions involving the oral cavity/soft palate with the following diagnoses: PLGA, pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). A total of 202 minor salivary gland neoplasms were included in the study. Among cases in which surface epithelium was present for evaluation (n=112), surface papillary epithelial hyperplasia was evident in 30% of PLGA and 1% of non-PLGA (i.e., MEC, ACC, PA). The greater frequency of surface papillary epithelial hyperplasia in the PLGA versus non-PLGA cases and in the benign versus malignant cases was significant (p=.0001 and p=.041, respectively). The sensitivity and specificity of papillary epithelial hyperplasia for PLGA were 30% (95% confidence interval (CI) 11.97-54.27%) and 99% (95% CI 94-99.82%), respectively. The clinical presentation of PLGA appeared relatively nonspecific, with all analyzed tumor types exhibiting a predilection for females, middle-aged to older adults, palatal location, pink/tan/normal color, and firm consistency. In conclusion, papillary epithelial hyperplasia was evident in only a minority of PLGA. However, when present within the context of a palatal salivary gland neoplasm, it appears to indicate a high probability of PLGA. Accordingly, rough mucosa may be a useful clinical pearl for identification of PLGA. PMID:25322702

  8. Sephadex and sephadex ion-exchange filtration improves the quality and freezability of low-grade buffalo semen ejaculates.

    PubMed

    Ahmad, Z; Anzar, M; Shahab, M; Ahmad, N; Andrabi, S M H

    2003-03-01

    The effect of sephadex and sephadex ion-exchange filtration on the improvement in quality and freezability of low-grade buffalo semen ejaculates was assessed. Two types of filtration columns were used: one containing only sephadex G-10 (FS) and the other sephadex G-10 along with ion-exchangers (diethyl amino ethane-52 (DEAE-52) cellulose and carboxy methyl-52 (CM-52) cellulose; FS+IE). Unfiltered samples served as controls. Semen ejaculates extended in Tris-citric acid (1:4) (n=16; initial motility 40-50%) were filtered at the rate of 1.5 ml/min under negative pressure at room temperature (28-30 degrees C). The mean recovery rate (%) of motile spermatozoa in the FS (85.9+/-1.51) and FS+IE (77.10+/-2.28) filtrates did not differ significantly. Percentages of sperm motility, normal acrosomes, and intact plasma membranes were highest (P<0.05) in FS+IE, intermediate (P<0.05) in FS and lowest (P<0.05) in controls at the three stages of cryopreservation (postfiltration final dilution, after equilibration, and after freezing). Mean sperm abnormalities were lowest (P<0.05) in the filtrates of FS+IE, moderate (P<0.05) in FS and highest in controls at all stages of freezing. Compared to dilution and equilibration, freezing greatly reduced (P<0.05) the overall percent motility, normal acrosomes and intact plasma membranes. The spermatozoa eluted through FS+IE columns proved more resistant (P<0.05) in bearing dilution, equilibration, freezing and thawing stresses than the spermatozoa from FS and control samples. It is concluded that filtration systems containing an FS+IE column can effectively enhance the quality and freezability of extended, low quality buffalo semen. PMID:12527067

  9. Hydrometallurgical recovery of heavy metals from low grade automobile shredder residue (ASR): An application of advanced Fenton process (AFP).

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-09-15

    To investigate the leaching and recovery of heavy metals from low-grade automobile shredder residue (ASR), the effects of nitric acid (HNO3) and hydrogen peroxide (H2O2) concentrations, liquid/solid (L/S) ratio, leaching temperature and ASR particle size fractions on the heavy metal leaching rate were determined. The heavy metals were recovered by fractional precipitation and advanced Fenton process (AFP) at different pHs. The toxicity characteristic leaching procedure (TCLP) test was also performed in the residue remaining after heavy metal leaching to evaluate the potential toxicity of ASR. The heavy metal leaching efficiency was increased with increasing HNO3 and H2O2 concentrations, L/S ratio and temperature. The heavy metal leaching efficiencies were maximized in the lowest ASR size fraction at 303K and L/S ratio of 100mL/g. The kinetic study showed that the metal leaching was best represented by a second-order reaction model, with a value of R(2)>0.99 for all selected heavy metals. The determined activation energy (kJ/mol) was 21.61, 17.10, 12.15, 34.50, 13.07 and 11.45 for Zn, Fe, Ni, Pb, Cd and Cr, respectively. In the final residue, the concentrations of Cd, Cr and Pb were under their threshold limits in all ASR size fractions. Hydrometallurgical metal recovery was greatly increased by AFP up to 99.96% for Zn, 99.97% for Fe, 95.62% for Ni, 99.62% for Pb, 94.11% for Cd and 96.79% for Cr. AFP is highly recommended for the recovery of leached metals from solution even at low concentrations. PMID:26143080

  10. Resecting diffuse low-grade gliomas to the boundaries of brain functions: a new concept in surgical neuro-oncology.

    PubMed

    Duffau, H

    2015-12-01

    The traditional dilemma making surgery for diffuse low-grade gliomas (DLGGs) challenging is underlain by the need to optimize tumor resection in order to significantly increase survival versus the risk of permanent neurological morbidity. Development of neuroimaging led neurosurgeons to achieve tumorectomy according to the oncological limits provided by preoperative or intraoperative structural and metabolic imaging. However, this principle is not coherent, neither with the infiltrative nature of DLGGs nor with the limited resolution of current neuroimaging. Indeed, despite technical advances, MRI still underestimates the actual spatial extent of gliomas, since tumoral cells are present several millimeters to centimeters beyond the area of signal abnormalities. Furthermore, cortical and subcortical structures may be still crucial for brain functions despite their invasion by this diffuse tumoral disease. Finally, the lack of reliability of functional MRI has also been demonstrated. Therefore, to talk about "maximal safe resection" based upon neuroimaging is a non-sense, because oncological MRI does not show the tumor and functional MRI does not show critical neural pathways. This review proposes an original concept in neuro-oncological surgery, i.e. to resect DLGG to the boundaries of brain functions, thanks to intraoperative electrical mapping performed in awake patients. This paradigmatic shift from image-guided resection to functional mapping-guided resection, based upon an accurate study of brain connectomics and neuroplasticity in each patient throughout tumor removal has permitted to solve the classical dilemma, by increasing both survival and quality of life in DLGG patients. With this in mind, brain surgeons should also be neuroscientists. PMID:25907410

  11. p53 protein in low-grade astrocytomas: a study with long-term follow-up.

    PubMed Central

    Iuzzolino, P.; Ghimenton, C.; Nicolato, A.; Giorgiutti, F.; Fina, P.; Doglioni, C.; Barbareschi, M.

    1994-01-01

    The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive. Images Figure 1 PMID:8123492

  12. Reorganization of Language Areas in Patient with a Frontal Lobe Low Grade Glioma fMRI Case Study

    PubMed Central

    Ko?la, Katarzyna; Bryszewski, Bartosz; Jasklski, Dariusz; B?asiak-Ko?aci?ska, Nina; Stefa?czyk, Ludomir; Majos, Agata

    2015-01-01

    Summary Background Functional magnetic resonance (fMRI) studies results in case of an adult patient with low grade glioma (LGG) in dominant hemisphere suggest brain plasticity process with acquisition of language functions by the non-dominant hemisphere speech regions. Case Report A 36-years old right-handed woman was admitted to the Department of Neurosurgery for surgical treatment of brain tumor. An MRI examination revealed a pathological mass in the left frontal lobe, in close topographical relationship to the Brocas area. A left fronto-parietal craniotomy was performed, with an intraoperative awake language mapping procedure. A total resection of the pathological mass was achieved. The tumor was examined histologically as LGG. In the follow-up MRI exam 32 months after the operation a tumor recurrence was suggested. The fMRI exams performed preoperative and 3, 32 and 41 months after the operation showed changes in language regions activation patterns, with a progressive right-sided activation of Brocas and Wernickes areas. Pre- and postoperative cognitive evaluation by a neuropsychologist did not detect any language impairment. We present a running process of reorganization of language areas in a patient after brain tumor resection, from strong left-sided to symmetrical lateralization. Conclusions 1. FMRI results in comparison with the psychological status of the patient proved contribution of functional reorganization to the preservation of language performance. 2. A slow growing LGG as well as the recurrence of the tumor near the left Brocas area might be the factors leading to reorganization of language-related areas by recruiting the right hemisphe. PMID:26097525

  13. Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer

    PubMed Central

    POYET, CDRIC; HERMANNS, THOMAS; ZHONG, QING; DRESCHER, EVA; EBERLI, DANIEL; BURGER, MAXIMILIAN; HOFSTAEDTER, FERDINAND; HARTMANN, ARNDT; STHR, ROBERT; ZWARTHOFF, ELLEN C.; SULSER, TULLIO; WILD, PETER J.

    2015-01-01

    In addition to conventional clinicopathological parameters, molecular markers are also required in order to predict the course of disease in patients with urothelial bladder cancer (BC). Little is known about fibroblast growth factor receptor 3 (FGFR3) immunoreactivity and the clinical significance it may possess with regard to BC. The present study aimed to investigate the immunoreactivity of FGFR3 in primary urothelial bladder tumours, with regard to clinicopathological features and FGFR3 mutation status. Tissue microarrays were used to immunohistochemically analyse FGFR3 expression in 255 primary, unselected patients with BC. FGFR3 mutations were detected using SNaPshot analysis. Positive FGFR3 immunoreactivity was identified in 113/207 analysable cases (54.6%), and was significantly associated with FGFR3 mutation (P<0.001), low tumour stage (P<0.001), low histological grade (P<0.001) and a papillary growth pattern (P<0.001). Positive FGFR3 immunostaining (P=0.002) and FGFR3 mutation (P=0.002) were found to be significantly associated with increased disease-specific survival following univariate analysis, demonstrating a median follow-up period of 75 months. Using multivariate analyses, FGFR3 immunoreactivity was found not to be independent of classical pathological parameters. Immunohistochemical expression of FGFR3 is an early occurrence during the carcinogenesis of papillary non-invasive BC. The presence of FGFR3 immunoreactivity in non-invasive papillary urothelial carcinomas may be utilised as an indicator of tumours possessing low-grade features and good prognosis. PMID:26722237

  14. Hyperleptinemia is associated with parameters of low-grade systemic inflammation and metabolic dysfunction in obese human beings

    PubMed Central

    Leon-Cabrera, Sonia; Sols-Lozano, Lourdes; Surez-lvarez, Karina; Gonzlez-Chvez, Antonio; Bjar, Yadira L.; Robles-Daz, Guillermo; Escobedo, Galileo

    2013-01-01

    Leptin is an adipose tissue-derived hormone that has been involved in hypothalamic and systemic inflammation, altered food-intake patterns, and metabolic dysfunction in obese mice. However, it remains unclear whether leptin has a relationship with parameters of systemic inflammation and metabolic dysfunction in humans. We thus evaluated in a cross-sectional study the circulating levels of leptin in 40 non-obese and 41 obese Mexican individuals, examining their relationship with tumor necrosis factor alpha (TNF-?), interleukin (IL) 12, IL-10, central obesity, serum glucose and insulin levels, and serum triglyceride and cholesterol concentrations. Circulating levels of leptin, TNF-?, IL-12, IL-10, and insulin were measured by ELISA, while concentrations of glucose, triglyceride, and cholesterol were determined by enzymatic assays. As expected, serum levels of leptin exhibited a significant elevation in obese individuals as compared to non-obese subjects, showing a clear association with increased body mass index (r = 0.4173), central obesity (r = 0.4678), and body fat percentage (r = 0.3583). Furthermore, leptin also showed a strong relationship with serum TNF-? (r = 0.6989), IL-12 (r = 0.3093), and IL-10 (r = ?0.5691). Interestingly, leptin was also significantly related with high concentrations of fasting glucose (r = 0.5227) and insulin (r = 0.2229), as well as elevated levels of insulin resistance (r = 0.3611) and circulating triglyceride (r = 0.4135). These results suggest that hyperleptinemia is strongly associated with the occurrence of low-grade systemic inflammation and metabolic alteration in obese subjects. Further clinical research is still needed to determine whether hyperleptinemia may be a potential marker for recognizing the advent of obesity-related metabolic disorders in human beings. PMID:23986664

  15. Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

    PubMed Central

    Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

    2014-01-01

    Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a gold standard was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior. PMID:24784396

  16. KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma

    PubMed Central

    Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok

    2014-01-01

    BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCRSanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCRSanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645

  17. Low-Grade Dysplasia in Ulcerative Colitis: Risk Factors for Developing High-Grade Dysplasia or Colorectal Cancer

    PubMed Central

    Choi, Chang-ho Ryan; Ignjatovic-Wilson, Ana; Askari, Alan; Lee, Gui Han; Warusavitarne, Janindra; Moorghen, Morgan; Thomas-Gibson, Siwan; Saunders, Brian P; Rutter, Matthew D; Graham, Trevor A; Hart, Ailsa L

    2015-01-01

    OBJECTIVES: The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD). METHODS: Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark's Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC. RESULTS: A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 1587 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.024.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.313.4; P=0.02) dysplasia, dysplastic lesions ?1?cm in size (HR, 3.8; 95% CI, 1.513.4; P=0.01), and a previous history of indefinite for dysplasia (HR, 2.8; 95% CI, 1.26.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.97.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.67.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.522.1; P<0.001) showed only univariate correlation to development of HGD or CRC. CONCLUSIONS: Lesions that are non-polypoid or endoscopically invisible, large (?1?cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD. PMID:26416190

  18. Provenance of Paleozoic very low- to low-grade metasedimentary rocks of South Tisia (Slavonian Mountains, Radlovac Complex, Croatia)

    NASA Astrophysics Data System (ADS)

    Bievac, Vanja; Krenn, Erwin; Finger, Fritz; Luar-Oberiter, Borna; Balen, Draen

    2013-02-01

    Monazite age dating, detrital heavy mineral content and whole-rock geochemistry provided insight into the provenance, depositional history and paleogeological setting of the Radlovac Complex very low- to low-grade metasedimentary rocks (South Tisia, Slavonian Mountains, Croatia). Electron microprobe based Th-U-Pb dating of detrital monazite indicates a Variscan age of the protolith (330 10 Ma). The detrital heavy mineral assemblages of representative metasedimentary rocks are dominated by apatite, zircon, tourmaline and rutile accompanied by minor quantity of epidote/zoisite, monazite and titanite. Judging from the heavy mineral assemblage, felsic igneous rocks served as the source material. This is consistent with the major and trace element spectrum of studied metasedimentary rocks characterized by high concentration of Th, high L + MREEs and high ratios of La/Sc, Th/Sc, La/Co, Th/Co and Th/Cr. The occurrence of magmatic monazite, zircon and xenotime and the absence of metamorphic heavy minerals suggest that granitoids, migmatites and migmatitic gneisses served as one major source for the metapsammites. Such rock types are commonly exposed in the Papuk Complex of the older surrounding complexes, while the Psunj Complex also contains metamorphic rocks. This is in good correlation with the monazite ages presented here which fits better with ages of Papuk Complex representative rocks than with those of the Psunj Complex known from the literature. Overall, data show that the Radlovac Complex represents the detritus of the local Variscan crust characterized by granitoid bodies, migmatites and migmatitic gneisses typical for the Papuk Complex.

  19. Genetic and epigenetic characterization of low-grade gliomas reveals frequent methylation of the MLH3 gene.

    PubMed

    Lhotska, Halka; Zemanova, Zuzana; Cechova, Hana; Ransdorfova, Sarka; Lizcova, Libuse; Kramar, Filip; Krejcik, Zdenek; Svobodova, Karla; Bystricka, Dagmar; Hrabal, Petr; Dohnalova, Alena; Michalova, Kyra

    2015-11-01

    Diffuse astrocytomas and oligodendrogliomas (WHO grade II) are the most common histological subtypes of low-grade gliomas (LGGs). Several molecular and epigenetic markers have been identified that predict tumor progression. Our aim was in detail to investigate the genetic and epigenetic background of LGGs and to identify new markers that might play a role in tumor behavior. Twenty-three patients with oligodendroglioma or oligoastrocytoma (LGO) and 22 patients with diffuse astrocytoma (LGA) were investigated using several molecular-cytogenetic and molecular methods to assess their copy number variations, mutational status and level of promoter methylation. The most frequent findings were a 1p/19q codeletion in 83% of LGO and copy-neutral loss of heterozygosity (CN-LOH) of 17p in 72% of LGA. Somatic mutations in the isocitrate dehydrogenase 1 or 2 (IDH1/IDH2) genes were detected in 96% of LGO and 91% of LGA. The O-6-methylguanine-DNA-methyltransferase (MGMT) promoter was methylated in 83% of LGO and 59% of LGA. MutL homolog 3 (MLH3) promoter methylation was observed in 61% of LGO and 27% of LGA. Methylation of the MGMT promoter, 1p/19q codeletion, mutated IDH1, and CN-LOH of 17p were the most frequent genetic aberrations in LGGs. The findings were more diverse in LGA than in LGO. To the best of our knowledge, this is the first time description of methylation of the MLH3 gene promoter in LGGs. Further studies are required to determine the role of the methylated MLH3 promoter and the other aberrations detected. PMID:26303387

  20. Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions

    PubMed Central

    Brismar-Wendel, S; Froberg, M; Hjerpe, A; Andersson, S; Johansson, B

    2009-01-01

    Background: To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Materials and methods: 343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland). Results: High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P=0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend. Conclusions: After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination. PMID:19623178

  1. Design and Numerical Simulation of a Symbiotic Thermoelectric Power Generation System Fed by a Low-Grade Heat Source

    NASA Astrophysics Data System (ADS)

    Faraji, Amir Yadollah; Singh, Randeep; Mochizuki, Masataka; Akbarzadeh, Aliakbar

    2014-06-01

    All liquid heating systems, including solar thermal collectors and fossil-fueled heaters, are designed to convert low-temperature liquid to high-temperature liquid. In the presence of low- and high-temperature fluids, temperature differences can be created across thermoelectric devices to produce electricity so that the heat dissipated from the hot side of a thermoelectric device will be absorbed by the cold liquid and this preheated liquid enters the heating cycle and increases the efficiency of the heater. Consequently, because of the avoidance of waste heat on the thermoelectric hot side, the efficiency of heat-to-electricity conversion with this configuration is better than that of conventional thermoelectric power generation systems. This research aims to design and analyze a thermoelectric power generation system based on the concept described above and using a low-grade heat source. This system may be used to generate electricity either in direct conjunction with any renewable energy source which produces hot water (solar thermal collectors) or using waste hot water from industry. The concept of this system is designated "ELEGANT," an acronym from "Efficient Liquid-based Electricity Generation Apparatus iNside Thermoelectrics." The first design of ELEGANT comprised three rectangular aluminum channels, used to conduct warm and cold fluids over the surfaces of several commercially available thermoelectric generator (TEG) modules sandwiched between the channels. In this study, an ELEGANT with 24 TEG modules, referred to as ELEGANT-24, has been designed. Twenty-four modules was the best match to the specific geometry of the proposed ELEGANT. The thermoelectric modules in ELEGANT-24 were electrically connected in series, and the maximum output power was modeled. A numerical model has been developed, which provides steady-state forecasts of the electrical output of ELEGANT-24 for different inlet fluid temperatures.

  2. IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.

    PubMed

    Barone, Francesca; Nayar, Saba; Campos, Joana; Cloake, Thomas; Withers, David R; Toellner, Kai-Michael; Zhang, Yang; Fouser, Lynette; Fisher, Benjamin; Bowman, Simon; Rangel-Moreno, Javier; Garcia-Hernandez, Maria de la Luz; Randall, Troy D; Lucchesi, Davide; Bombardieri, Michele; Pitzalis, Costantino; Luther, Sanjiv A; Buckley, Christopher D

    2015-09-01

    The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions. PMID:26286991

  3. IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs

    PubMed Central

    Barone, Francesca; Nayar, Saba; Campos, Joana; Cloake, Thomas; Withers, David R.; Toellner, Kai-Michael; Zhang, Yang; Fouser, Lynette; Fisher, Benjamin; Bowman, Simon; Rangel-Moreno, Javier; Garcia-Hernandez, Maria de la Luz; Randall, Troy D.; Lucchesi, Davide; Bombardieri, Michele; Pitzalis, Costantino; Luther, Sanjiv A.; Buckley, Christopher D.

    2015-01-01

    The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22blocking agents in B-cellmediated autoimmune conditions. PMID:26286991

  4. Neoplastic diseases of the haematopoietic and lymphoid tissues*

    PubMed Central

    Jarrett, W. F. H.; Mackey, L. J.

    1974-01-01

    Systemic lymphosarcomas are common in all species of domestic mammal. A binomial classification of these tumours, based on both the anatomical form (i.e., distribution of lesions) and the type of cytology, is proposed. Mast cell tumours also are common, especially in the dog. The categories of lymphoid neoplasms described are: lymphosarcoma, lymphoid leukaemia, nodular lymphoid hyperplasia, tumours of the immunoglobulin-forming cells, and thymoma. The myeloid neoplasms described are: myeloid leukaemia, erythroleukaemia, acute erythraemia, polycythaemia vera, megakaryocytoid leukaemia, panmyelosis, myelosclerosis, and monocytoid leukaemia. Mast cell tumours are divided into mastocytoma and malignant mastocytosis. ImagesPLATE IIFig. 13Fig. 14PLATE IPLATE IIIFig. 9Fig. 10Fig. 11Fig. 12Fig. 5Fig. 6Fig. 7Fig. 8Fig. 1Fig. 2Fig. 3Fig. 4 PMID:4214049

  5. CCL21 Expression Pattern of Human Secondary Lymphoid Organ Stroma Is Conserved in Inflammatory Lesions with Lymphoid Neogenesis

    PubMed Central

    Manzo, Antonio; Bugatti, Serena; Caporali, Roberto; Prevo, Remko; Jackson, David G.; Uguccioni, Mariagrazia; Buckley, Christopher D.; Montecucco, Carlomaurizio; Pitzalis, Costantino

    2007-01-01

    CCL21 is a homeostatic lymphoid chemokine instrumental in the recruitment and organization of T cells and dendritic cells into lymphoid T areas. In human secondary lymphoid organs (SLOs), CCL21 is produced by cells distributed throughout the T zone, whereas high endothelial venules (HEVs) lack CCL21 mRNA. A critical question remains whether the development of ectopic lymphoid tissue (ELT) in chronic inflammation recapitulates the features of SLOs. Thus, we systematically investigated in situ the cellular sources of CCL21 in SLOs and ELTs in several human diseases characterized by lymphoid neogenesis. By in situ hybridization and the use of combinatorial cell markers, we show that CCL21-producing vessels in inflamed tissues systematically display typical markers of lymphatic vessels, whereas, as in SLOs, ectopic HEVs do not synthesize detectable levels of CCL21. We also provide first-time evidence that a common pattern of CCL21 expression by CD45-negative myofibroblast-like cells localized in extra-HEV position and organized in a fibroblastic reticular network similarly characterizes human SLOs and organized ELTs. Altogether, our results demonstrate that in humans the pattern of CCL21 production in SLOs is maintained during inflammation and that the phenotypic and functional properties of stromal cells, found in SLO T-cell areas, are reproduced at ectopic sites. PMID:17982129

  6. Association between low-grade albuminuria and hearing impairment in a non-diabetic Korean population: The Korea National Health and Nutrition Examination Survey (2011-2013).

    PubMed

    Kang, Seok Hui; Jung, Da Jung; Choi, Eun Woo; Park, Jong Won; Cho, Kyu Hyang; Yoon, Kyung Woo; Do, Jun Young

    2015-12-01

    Introduction The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. Materials and methods Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study if they were younger than 19 years old, or had urine albumin/creatinine ratio (UACR)???30?mg/g or diabetes mellitus. There were 10?608 participants included in this study. The participants were divided into three groups according to their UACR tertiles. Results There were 1560; 1561; and 1552 male and 1982; 1975; and 1978, female participants in the low, middle, and high tertile groups, respectively. The results indicated the association between low-grade albuminuria and the numbers of metabolic syndrome (MetS) components or Framingham risk score, and the presence of MetS or the proportions of participants at high cardiovascular risk. Univariate and multivariate linear regression analyses demonstrated an association between the UACR and average hearing threshold (AHT) that was observed in both sexes. Multivariate analyses showed that mean AHTs in the low, middle, and high tertile groups were, respectively, 16.127 dB, 17.139 dB, and 18.604 dB for men, and 14.842 dB, 15.100 dB, and 16.353 dB, respectively, for women. Low-frequency, mid-frequency, and high-frequency hearing thresholds according to UACR tertiles showed similar trends. In both sexes, multivariate logistic regression analyses revealed that participants in the low and middle tertile groups had a decreased risk for hearing loss compared to participants in the high tertile group. Conclusion Low-grade albuminuria was associated with hearing impairment in the non-diabetic participants of this study. Key messages Low-grade albuminuria is associated with MetS and cardiovascular risk in the non-diabetic population. Low-grade albuminuria is associated with hearing thresholds and hearing loss in the non-diabetic population. Participants with low-grade albuminuria may be closely monitored for hearing impairment. PMID:26542850

  7. [Meningeal tertiary lymphoid organs: Major actors in intrathecal autoimmunity].

    PubMed

    Bonnan, M

    2015-01-01

    Multiple sclerosis (MS) is characterized by an intrathecal synthesis of immunoglobulins synthesized by B-cell clones and by a brain infiltrate of clonal T-cells. The clonal maturation of these lymphocytes takes place in tertiary lymphoid organs (TLO) developed in the intrathecal compartment. TLO are acquired lymphoid organs able to develop in the vicinity of the inflammatory sites, where they mount a complete antigen-driven immune response. We here review TLO pathophysiology in animal models of MS and human MS. Several pieces of evidence suggest that intrathecal TLO may play a major role in the clinical impairment. Potential therapeutic applications are examined. PMID:25555848

  8. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    SciTech Connect

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-04-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here.

  9. Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage.

    PubMed

    Ishizuka, Isabel E; Chea, Sylvestre; Gudjonson, Herman; Constantinides, Michael G; Dinner, Aaron R; Bendelac, Albert; Golub, Rachel

    2016-03-01

    The precise lineage relationship between innate lymphoid cells (ILCs) and lymphoid tissue-inducer (LTi) cells is poorly understood. Using single-cell multiplex transcriptional analysis of 100 lymphoid genes and single-cell cultures of fetal liver precursor cells, we identified the common proximal precursor to these lineages and found that its bifurcation was marked by differential induction of the transcription factors PLZF and TCF1. Acquisition of individual effector programs specific to the ILC subsets ILC1, ILC2 and ILC3 was initiated later, at the common ILC precursor stage, by transient expression of mixed ILC1, ILC2 and ILC3 transcriptional patterns, whereas, in contrast, the development of LTi cells did not go through multilineage priming. Our findings provide insight into the divergent mechanisms of the differentiation of the ILC lineage and LTi cell lineage and establish a high-resolution 'blueprint' of their development. PMID:26779601

  10. The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

    PubMed Central

    Thomsen, Henrik H; Mller, Holger J; Trolle, Christian; Groth, Kristian A; Skakkebk, Anne; Bojesen, Anders; Hst, Christian; Gravholt, Claus H

    2013-01-01

    Soluble CD163 (sCD163) is a novel marker linked to states of low-grade inflammation such as diabetes, obesity, liver disease, and atherosclerosis, all prevalent in subjects with Turner syndrome (TS) and Klinefelter syndrome (KS). We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards to treatment with sex hormone therapy in males with and without KS and females with and without TS. Males with KS (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study. Females with TS (n=8) and healthy age-matched controls (n=8) participating in a randomized crossover trial. The intervention comprised of treatment with sex steroids. Males with KS had higher levels of sCD163 compared with controls (1.75 (0.476.90) and 1.36 (0.773.11) respectively, P<0.001) and the levels correlated to plasma testosterone (r=?0.31, P<0.01), BMI (r=0.42, P<0.001), and homeostasis model of assessment insulin resistance (r=0.46, P<0.001). Treatment with testosterone did not significantly lower sCD163. Females with TS not receiving hormone replacement therapy (HRT) had higher levels of sCD163 than those of their age-matched healthy controls (1.380.44 vs 0.910.40, P=0.04). HRT and oral contraceptive therapy decreased sCD163 in TS by 22% (1.070.30) and in controls by 39% (0.550.36), with significance in both groups (P=0.01 and P=0.04). We conclude that levels of sCD163 correlate with endogenous testosterone in KS and are higher in KS subjects compared with controls, but treatment did not significantly lower levels. Both endogenous and exogenous estradiol in TS was associated with lower levels of sCD163. PMID:24148221

  11. 40Ar/39Ar and K/Ar dating of low grade metamorphism: examples on metabasites from Central Chile

    NASA Astrophysics Data System (ADS)

    Aguirre, L.; Feraud, G.; Fuentes, F.; Delbar, M.; Morata, D.

    2003-04-01

    Dating low to very low-grade burial metamorphic assemblages is often difficult because of (1) few mineral phases compositionally suitable to apply the 40Ar/39Ar and K-Ar methods, and (2) small amount in which these phases are commonly found. K-feldspar adularia, sericitic mica, and celadonite are the best known K-bearing secondary minerals. We present some successful attempts to analyse two distinct secondary phases from a same volcanic formation that allow to test the validity of the measured ages. These ages have been also compared with the crystallisation age of the volcanic rocks in which the secondary phases were lately developed. Adularia and sericite were selected from basic lava flows from a 3 to 13 km thick Cretaceous sequence from the Coastal Range of central Chile, at two different locations: the Bustamante Hill (west from Santiago), and the Cordn de Chacana, c. 80 km further north. Adularia came from a low-variance assemblage with pumpellyite, chlorite and low-albite contained in amygdules whereas sericite was present in milky-white strongly sericitized plagioclase crystals. While small clusters of rare fresh plagioclase grains from lava flows from Bustamante and Chacana displayed concordant plateau ages 119.4 2.4 (2 sigma) and 118.7 0.6 Ma, respectively, the adularia from the same formations gave sensibly younger ages around 94 Ma (high temperature steps), and 96.8 0.2 Ma (plateau age) in Bustamante and Chacana, respectively. Sericite ages were measured in situ into single crystals of strongly transformed plagioclases. The relative proportion of sericite and plagioclase corresponding to each degasing step was monitored by measuring the Ca/K ratio (deduced from 37ArCa/39Ar_K). While intermediate ages were measured on some sericite of both sites (corresponding to a variable but permanent contribution of plagioclase on each step), a plateau age of 97.0 1.6 Ma (concordant with adularia) could be obtained on a strongly sericitized plagioclase from Chacana. Thus, an apparently reliable time interval of about 25 and 22 Ma between the volcanic and the metamorphic events could be obtained in Bustamante and Chacana respectively. K-Ar celadonite ages ranging from 101 3 to 108 4 Ma have been obtained for Jurassic lavas from the Andean Cordillera c. 200 km south from Santiago whereas celadonite in Oligocene lavas from the same region gave a K-Ar age of 19.1 0.8 Ma. These values suggest the existence of two metamorphic events of Cretaceous and Miocene age.

  12. Beneficial impact of high-field intraoperative magnetic resonance imaging on the efficacy of pediatric low-grade glioma surgery.

    PubMed

    Roder, Constantin; Breitkopf, Martin; Ms; Bisdas, Sotirios; Freitas, Rousinelle da Silva; Dimostheni, Artemisia; Ebinger, Martin; Wolff, Markus; Tatagiba, Marcos; Schuhmann, Martin U

    2016-03-01

    OBJECTIVE Intraoperative MRI (iMRI) is assumed to safely improve the extent of resection (EOR) in patients with gliomas. This study focuses on advantages of this imaging technology in elective low-grade glioma (LGG) surgery in pediatric patients. METHODS The surgical results of conventional and 1.5-T iMRI-guided elective LGG surgery in pediatric patients were retrospectively compared. Tumor volumes, general clinical data, EOR according to reference radiology assessment, and progression-free survival (PFS) were analyzed. RESULTS Sixty-five patients were included in the study, of whom 34 had undergone conventional surgery before the iMRI unit opened (pre-iMRI period) and 31 had undergone surgery with iMRI guidance (iMRI period). Perioperative data were comparable between the 2 cohorts, apart from larger preoperative tumor volumes in the pre-iMRI period, a difference without statistical significance, and (as expected) significantly longer surgeries in the iMRI group. According to 3-month postoperative MRI studies, an intended complete resection (CR) was achieved in 41% (12 of 29) of the patients in the pre-iMRI period and in 71% (17 of 24) of those in the iMRI period (p = 0.05). Of those cases in which the surgeon was postoperatively convinced that he had successfully achieved CR, this proved to be true in only 50% of cases in the pre-iMRI period but in 81% of cases in the iMRI period (p = 0.055). Residual tumor volumes on 3-month postoperative MRI were significantly smaller in the iMRI cohort (p < 0.03). By continuing the resection of residual tumor after the intraoperative scan (when the surgeon assumed that he had achieved CR), the rate of CR was increased from 30% at the time of the scan to 85% at the 3-month postoperative MRI. The mean follow-up for the entire study cohort was 36.9 months (3-79 months). Progression-free survival after surgery was noticeably better for the entire iMRI cohort and in iMRI patients with postoperatively assumed CR, but did not quite reach statistical significance. Moreover, PFS was highly significantly better in patients with CRs than in those with incomplete resections (p < 0.001). CONCLUSIONS Significantly better surgical results (CR) and PFS were achieved after using iMRI in patients in whom total resections were intended. Therefore, the use of high-field iMRI is strongly recommended for electively planned LGG resections in pediatric patients. PMID:26926053

  13. Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

    SciTech Connect

    Daniels, Thomas B.; Brown, Paul D.; Felten, Sara J.; Wu, Wenting; Buckner, Jan C.; Arusell, Robert M.; Curran, Walter J.; Abrams, Ross A.; Schiff, David; Shaw, Edward G.

    2011-09-01

    Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.

  14. Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

    PubMed Central

    Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

    2011-01-01

    Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this infection, as well as monitoring for at least 1 year according to the natural evolution of the disease. PMID:24765393

  15. Dietary xylooligosaccharide downregulates IFN-γ and the low-grade inflammatory cytokine IL-1β systemically in mice.

    PubMed

    Hansen, Camilla H F; Frøkiær, Hanne; Christensen, Annette G; Bergström, Anders; Licht, Tine R; Hansen, Axel K; Metzdorff, Stine B

    2013-04-01

    Dietary carbohydrates improve growth conditions for distinct populations of bacteria that may affect mucosal and systemic immunity. In this study, we fed in a parallel experiment a 10% xylooligosaccharide (XOS)-supplemented diet or a control diet to 2 groups of male C57BL/6NTac mice for 10 wk from weaning. We found that the XOS diet significantly increased Bifidobacterium throughout the intestine compared with control-fed mice, with the highest proportions found in the ileum after XOS feeding (P < 0.001). In the intestinal epithelium, most innate immune-related genes were unaffected by XOS feeding, whereas expression of interleukin 1β (Il1β) (P < 0.01) and interferon γ (Ifnγ) (P < 0.05) was significantly less in blood from XOS-fed mice than from control-fed mice. In vitro treatment of blood with propionate significantly decreased Il1β (P < 0.01), Ifnγ (P < 0.01), and interleukin 18 (Il18) (P < 0.001) expression, supporting our hypothesis that increased production of short-chain fatty acids (SCFAs) in the gut, which are transported across the intestine and into the systemic compartments, results in downregulation of low-grade inflammatory cytokines. The defensin regenerating islet-derived protein 3γ (RegIIIγ) was significantly more highly expressed in the small intestine (P < 0.01) in XOS-fed mice compared with control-fed mice, suggesting only minor contact between bifidobacteria and epithelial cells. In support of this, the SCFA-induced sodium/hydrogen exchanger isoform 3 expression tended to be greater in the XOS group than in the control group (P = 0.06), indicating an indirect SCFA-mediated antiinflammatory effect of XOS. In conclusion, XOS feeding decreases systemic inflammation, and this effect is most likely caused by higher SCFA concentrations as a result of an increased bifidobacterial saccharolytic fermentation in the entire gut and not only in the large intestine. PMID:23427328

  16. TEM/AEM characterization of fine-grained clay minerals in very-low-grade rocks: Evaluation of contamination by EMPA involving celadonite family minerals

    SciTech Connect

    Li, Gejing; Peacor, D.R.; Coombs, D.S.; Kawachi, Y.

    1996-12-31

    Recent advances in transmission electron microscopy (TEM) and analytical electron microscopy (AEM) have led to many new insights into the structural and chemical characteristics of very fine-grained, optically homogeneous mineral aggregates in sedimentary and very low-grade metamorphic rocks. Chemical compositions obtained by electron microprobe analysis (EMPA) on such materials have been shown by TEM/AEM to result from beam overlap on contaminant phases on a scale below resolution of EMPA, which in turn can lead to errors in interpretation and determination of formation conditions. Here we present an in-depth analysis of the relation between AEM and EMPA data, which leads also to the definition of new mineral phases, and demonstrate the resolution power of AEM relative to EMPA in investigations of very fine-grained mineral aggregates in sedimentary and very low-grade metamorphic rocks.

  17. Reductive leaching of manganese from low-grade pyrolusite ore in sulfuric acid using pyrolysis-pretreated sawdust as a reductant

    NASA Astrophysics Data System (ADS)

    Feng, Ya-li; Zhang, Shi-yuan; Li, Hao-ran

    2016-03-01

    Manganese (Mn) leaching and recovery from low-grade pyrolusite ore were studied using sulfuric acid (H2SO4) as a leachant and pyrolysis-pretreated sawdust as a reductant. The effects of the dosage of pyrolysis-pretreated sawdust to pyrolusite ore, the concentration of sulfuric acid, the liquid/solid ratio, the leaching temperature, and the leaching time on manganese and iron leaching efficiencies were investigated. Analysis of manganese and iron leaching efficiencies revealed that a high manganese leaching efficiency was achieved with low iron extraction. The optimal leaching efficiency was determined to be 20wt% pyrolysis-pretreated sawdust and 3.0 mol/L H2SO4 using a liquid/ solid ratio of 6.0 mL/g for 90 min at 90°C. Other low-grade pyrolusite ores were tested, and the results showed that they responded well with manganese leaching efficiencies greater than 98%.

  18. Peripheral ameloblastoma with histologically low-grade malignant features of the buccal mucosa: a case report with immunohistochemical study and genetic analysis.

    PubMed

    Goda, Hiroyuki; Nakashiro, Kohichi; Ogawa, Ikuko; Takata, Takashi; Hamakawa, Hiroyuki

    2015-01-01

    Peripheral ameloblastoma (PA), a rare and unusual variant of odontogenic tumors, comprises about 1% of all ameloblastomas. PA is an exophytic growth localized to the soft tissues overlying the tooth-bearing areas of the jaws, and the initial diagnosis is often fibrous epulis. PA with histologically low-grade malignant features is extremely rare. We report a case of peripheral ameloblastoma with histologically low-grade malignant features in a 69-year-old woman that presented with a hemorrhage from a tumor on the right buccal mucosa. The tumor was surgically removed by blunt dissection, with no evidence of recurrence after two years and six months. After the case presentation, microscopic and genetic findings are discussed. PMID:25973109

  19. Peripheral ameloblastoma with histologically low-grade malignant features of the buccal mucosa: a case report with immunohistochemical study and genetic analysis

    PubMed Central

    Goda, Hiroyuki; Nakashiro, Kohichi; Ogawa, Ikuko; Takata, Takashi; Hamakawa, Hiroyuki

    2015-01-01

    Peripheral ameloblastoma (PA), a rare and unusual variant of odontogenic tumors, comprises about 1% of all ameloblastomas. PA is an exophytic growth localized to the soft tissues overlying the tooth-bearing areas of the jaws, and the initial diagnosis is often fibrous epulis. PA with histologically low-grade malignant features is extremely rare. We report a case of peripheral ameloblastoma with histologically low-grade malignant features in a 69-year-old woman that presented with a hemorrhage from a tumor on the right buccal mucosa. The tumor was surgically removed by blunt dissection, with no evidence of recurrence after two years and six months. After the case presentation, microscopic and genetic findings are discussed. PMID:25973109

  20. Two-peaked 5-ALA-induced PpIX fluorescence emission spectrum distinguishes glioblastomas from low grade gliomas and infiltrative component of glioblastomas

    PubMed Central

    Montcel, Bruno; Mahieu-Williame, Laurent; Armoiry, Xavier; Meyronet, David; Guyotat, Jacques

    2013-01-01

    5-ALA-induced protoporphyrin IX (PpIX) fluorescence enables to guiding in intra-operative surgical glioma resection. However at present, it has yet to be shown that this method is able to identify infiltrative component of glioma. In extracted tumor tissues we measured a two-peaked emission in low grade gliomas and in the infiltrative component of glioblastomas due to multiple photochemical states of PpIX. The second emission peak appearing at 620 nm (shifted by 14 nm from the main peak at 634 nm) limits the sensibility of current methods to measured PpIX concentration. We propose new measured parameters, by taking into consideration the two-peaked emission, to overcome these limitations in sensitivity. These parameters clearly distinguish the solid component of glioblastomas from low grade gliomas and infiltrative component of glioblastomas. PMID:23577290

  1. Fine needle aspiration cytology of histiocytic sarcoma with dendritic cell differentiation: a case of transdifferentiation from low-grade follicular lymphoma.

    PubMed

    Mehrotra, Sanjana; Pan, Zenggang

    2015-08-01

    Histiocytic sarcoma (HS) is a rare malignant tumor, and in extraordinary circumstances it can be transdifferentiated from a low-grade B-cell lymphoma. In our report, a 62-year-old female was initially diagnosed with a low-grade follicular lymphoma, and 2 years later she presented with bilateral lung masses and lymphadenopathy. Fine needle aspiration (FNA) of the lung masses revealed solid nests of large pleomorphic epithelioid cells. By immunohistochemical studies, the tumor cells were positive for histiocytic markers (CD68 and CD163) and S100, supporting a diagnosis of HS with dendritic cell differentiation. Further fluorescence in situ hybridization (FISH) analyses detected IGH@/BCL2 rearrangement in both the previous follicular lymphoma and the current HS, which was highly suggestive of the clonal relationship between these two tumors. To the best of our knowledge, this is the first case of transformation of follicular lymphoma into HS diagnosed by FNA of lung masses. PMID:25993973

  2. [Cervical myelopathy after low grade distortion of the cervical spine. Possible association with pre-existing spondylosis of the cervical spine].

    PubMed

    Aurich, M; Hofmann, G O; Gras, F M

    2015-04-01

    A patient with spondylosis deformans of the cervical spine with no neurological deficits developed rapidly progressive tetraparesis 1 day after a whiplash injury due to a car accident (rear end collision), although initially there were no clinical symptoms. Surgical decompression and spondylodesis led to relief of the neurological deficits. This case demonstrates that even a low grade whiplash injury (grade 1) can cause severe neurological symptoms later and that a degenerative disease of the spine is a predisposing factor. PMID:25336350

  3. Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection.

    PubMed

    Fend, F; Quintanilla-Martinez, L; Kumar, S; Beaty, M W; Blum, L; Sorbara, L; Jaffe, E S; Raffeld, M

    1999-06-01

    Low grade B-cell lymphomas comprise several well defined, clinically and immunophenotypically distinct disease entities. Composite lymphomas showing phenotypic characteristics of more than one of these tumor subtypes in the same site are rare, and both common and separate clonal origins of the two tumor parts have been reported for cases studied by molecular methods. We describe the detailed immunohistochemical and molecular findings in three cases with features of composite low grade B-cell non-Hodgkin's lymphoma (B-NHL). All three neoplasms contained morphologically distinct but interwoven compartments of different cell types, which exhibited discordant expression of several markers, including CD5, CD10, CD43, and cyclin D1. According to their morphology and phenotypes, they were classified as mantle cell lymphoma and follicular lymphoma (Case 1), follicular lymphoma and small lymphocytic lymphoma (Case 2), and mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (Case 3). PCR analysis of DNA obtained from whole tissue sections failed to reveal evidence for biclonality in any of the cases. We therefore isolated cell populations with different antigen expression patterns by laser capture microdissection and analyzed them by polymerase chain reaction amplification and sequencing of clonal immunoglobulin heavy chain gene rearrangements and oncogene rearrangements. Sequence analysis revealed unrelated clonal rearrangements in each of the two tumor parts in all three cases, suggesting distinct clonal origins. In addition, Case 1 showed a bcl-2 rearrangement present only in the follicular lymphoma part. Our findings suggest that low grade B-NHL with two distinct morphological and immunophenotypic patterns in the same anatomical site are frequently biclonal. This is in keeping with current classification schemes, which recognize subtypes of low grade B-NHL as separate disease entities. Furthermore, our analysis demonstrates the power of laser capture microdissection in revealing molecular microheterogeneity in complex neoplasms. PMID:10362812

  4. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    PubMed

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system. PMID:20544418

  5. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo... lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine... preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell...

  6. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Detection of avian lymphoid leukosis. 113.31 Section 113.31 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Standard Procedures §...

  7. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo... lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine... preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell...

  8. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo... lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine... preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell...

  9. Mechanisms and clinical applications of chromosomal instability in lymphoid malignancy.

    PubMed

    Krem, Maxwell M; Press, Oliver W; Horwitz, Marshall S; Tidwell, Timothy

    2015-10-01

    Lymphocytes are unique among cells in that they undergo programmed DNA breaks and translocations, but that special property predisposes them to chromosomal instability (CIN), a cardinal feature of neoplastic lymphoid cells that manifests as whole chromosome- or translocation-based aneuploidy. In several lymphoid malignancies translocations may be the defining or diagnostic markers of the diseases. CIN is a cornerstone of the mutational architecture supporting lymphoid neoplasia, though it is perhaps one of the least understood components of malignant transformation in terms of its molecular mechanisms. CIN is associated with prognosis and response to treatment, making it a key area for impacting treatment outcomes and predicting prognoses. Here we will review the types and mechanisms of CIN found in Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma and the lymphoid leukaemias, with emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair; telomere function; and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the means by which chromosome-level genetic aberrations may give rise to multiple pathogenic mutations required for carcinogenesis and conclude with a discussion of the clinical applications of CIN and aneuploidy to diagnosis, prognosis and therapy. PMID:26018193

  10. Direct effects of hepatitis C virus on the lymphoid cells.

    PubMed

    Kondo, Yasuteru; Shimosegawa, Tooru

    2013-11-28

    It has been reported that the direct binding of hepatitis C virus (HCV) and/or the replication of HCV in the extrahepatic organs and, especially, lymphoid cells, might affect the pathogenesis of extrahepatic diseases with HCV infection. More than one decade ago, several reports described the existence of HCV-RNA in peripheral blood mononuclear cells. Moreover, many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published. In addition to B lymphocytes, it was reported that HCV replication could be detected in T lymphocytes and T cell lines. Among the extrahepatic diseases with HCV infection, mixed cryoglobulinemia-related diseases and autoimmune-related diseases are important for understanding the immunopathogensis of HCV persistent infection. Moreover, HCV persistent infection can cause malignant lymphoma. The biological significance of lymphotropic HCV has not yet become clear. However, several candidates have been considered for a long time. One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficult-to-treat disease status. The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses. Therefore, the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells. In this article, we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV. PMID:24307783

  11. Direct effects of hepatitis C virus on the lymphoid cells

    PubMed Central

    Kondo, Yasuteru; Shimosegawa, Tooru

    2013-01-01

    It has been reported that the direct binding of hepatitis C virus (HCV) and/or the replication of HCV in the extrahepatic organs and, especially, lymphoid cells, might affect the pathogenesis of extrahepatic diseases with HCV infection. More than one decade ago, several reports described the existence of HCV-RNA in peripheral blood mononuclear cells. Moreover, many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published. In addition to B lymphocytes, it was reported that HCV replication could be detected in T lymphocytes and T cell lines. Among the extrahepatic diseases with HCV infection, mixed cryoglobulinemia-related diseases and autoimmune-related diseases are important for understanding the immunopathogensis of HCV persistent infection. Moreover, HCV persistent infection can cause malignant lymphoma. The biological significance of lymphotropic HCV has not yet become clear. However, several candidates have been considered for a long time. One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficult-to-treat disease status. The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses. Therefore, the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells. In this article, we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV. PMID:24307783

  12. IDing Innate and Innate-like Lymphoid Cells

    PubMed Central

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  13. 'Managing' the immune system with total lymphoid irradiation

    SciTech Connect

    Strober, S.

    1981-06-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis.

  14. 9 CFR 113.31 - Detection of avian lymphoid leukosis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., shall be done in chick embryo cell cultures. (1) Each vaccine virus, cytopathic to chick embryo... lymphoid leukosis virus can be propagated on cell culture during the 21-day growth period. If a vaccine... preparation of such questionable vaccine. (2) When cell cultures are tested, 5 ml of the final cell...

  15. Avian dendritic cells: Phenotype and ontogeny in lymphoid organs.

    PubMed

    Nagy, Nándor; Bódi, Ildikó; Oláh, Imre

    2016-05-01

    Dendritic cells (DC) are critically important accessory cells in the innate and adaptive immune systems. Avian DCs were originally identified in primary and secondary lymphoid organs by their typical morphology, displaying long cell processes with cytoplasmic granules. Several subtypes are known. Bursal secretory dendritic cells (BSDC) are elongated cells which express vimentin intermediate filaments, MHC II molecules, macrophage colony-stimulating factor 1 receptor (CSF1R), and produce 74.3+ secretory granules. Avian follicular dendritic cells (FDC) highly resemble BSDC, express the CD83, 74.3 and CSF1R molecules, and present antigen in germinal centers. Thymic dendritic cells (TDC), which express 74.3 and CD83, are concentrated in thymic medulla while interdigitating DC are found in T cell-rich areas of secondary lymphoid organs. Avian Langerhans cells are a specialized 74.3-/MHC II+ cell population found in stratified squamous epithelium and are capable of differentiating into 74.3+ migratory DCs. During organogenesis hematopoietic precursors of DC colonize the developing lymphoid organ primordia prior to immigration of lymphoid precursor cells. This review summarizes our current understanding of the ontogeny, cytoarchitecture, and immunophenotype of avian DC, and offers an antibody panel for the in vitro and in vivo identification of these heterogeneous cell types. PMID:26751596

  16. Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion.

    PubMed

    van Galen, Peter; Kreso, Antonija; Wienholds, Erno; Laurenti, Elisa; Eppert, Kolja; Lechman, Eric R; Mbong, Nathan; Hermans, Karin; Dobson, Stephanie; April, Craig; Fan, Jian-Bing; Dick, John E

    2014-01-01

    The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs. We found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation. Conversely, reducing ID2 expression levels increases lymphoid potential. Mechanistically, ID2 inhibits the transcription factor E47 to attenuate B-lymphoid priming in HSCs and progenitors. Strikingly, ID2 overexpression also results in a 10-fold expansion of HSCs in serial limiting dilution assays, indicating that early lymphoid transcription factors antagonize human HSC self-renewal. The relationship between lineage priming and self-renewal can be exploited to increase expansion of transplantable human HSCs and points to broader implications for other stem cell populations. PMID:24388174

  17. Ovine lentivirus lymphoid interstitial pneumonia. Rapid induction in neonatal lambs.

    PubMed Central

    Lairmore, M. D.; Rosadio, R. H.; DeMartini, J. C.

    1986-01-01

    For examination of the characteristics of lentivirus-induced pulmonary disease in an animal model, neonatal lambs were given intratracheal injections of high-and low-passage ovine lentivirus (OvLV) isolates. In 6 of 6 lambs inoculated with low-passage OvLV or OvLV from lung lavage fluid, lesions of lymphoid interstitial pneumonia (LIP) developed. In none of 7 lambs inoculated with a high-passage OvLV or 4 control lambs inoculated with medium alone or ultrafiltered lung fluid did lung lesions develop. Systemic distribution of lentivirus was greater and development of lentivirus antibody was more rapid in lambs inoculated with low-passage OvLV, compared with lambs inoculated with high passage OvLV. The number of lymphocytes in bronchoalveolar lavage samples was increased in lambs with lymphoid interstitial pneumonia. The development of lymphoid interstitial pneumonia was markedly accelerated, in comparison with previous reports of experimentally induced lentivirus pneumonia in sheep. In lentivirus-inoculated lambs pulmonary lesions developed comparable to lymphoid interstitial pneumonia associated with the acquired immunodeficiency syndrome and other human benign lymphoid disorders of the lung. Similarities between the disease manifestations and virologic properties of OvLV and human T-cell lymphotropic virus III argue for the relevance of OvLV-induced disease as a model for human retrovirus diseases. The ability of OvLV to cause accelerated pulmonary disease in neonates may be due to age-related susceptibility factors that enhance the pathogenicity of lentiviruses. Images Figure 1 Figure 2 Figure 3 PMID:3022591

  18. An appraisal of the bo method in very-low grade metamorphic studies; the s. mayo caledonides, w. ireland

    NASA Astrophysics Data System (ADS)

    Rice, A. H. N.; Williams, D. M.

    2003-04-01

    Two XRD methods are used to asses very-low grade metamorphic conditions in pelitic rocks; illite crystallinity (IC; D2q) and bo (). The former is a proxy for the temperature and the latter for the baric type (P/T gradient) during metamorphism. Although both methods are equally important in obtaining a view of the P-T conditions, the analytical approaches are very different. For IC, the <2 fraction is carefully separated, saturated, repeatedly washed and accurately transferred to slides. Whilst not `high-tech, the process is very time consuming. In contrast, the bo method is `bucket chemistry; the rock-powder is simply pressed sideways into powder mounts. The reason for the care with IC is that detrital micas could affect the result. The crudity of the bo method is because separating enough <2 material for a powder holder is impractical. But if detrital micas affect IC data, why do they not affect bo data? bo measurement from the IC slides has been regarded as unreliable, due to the low intensity of the (060) illite peak determined from the IC preparates. Elaborate determination of the errors in bo-wr analysis (sample, locality, preparation and deconvolution errors, but not machine error) gives a combined percentage error of 0.06995%. This seems very small, but note bo is quoted to 3 decimal places; it reflects an overall standard deviation of ~0.0063 . Samples from Palaeozoic sediments in the 10 or more terranes in the Caledonian S. Mayo Trough of W. Ireland, display bo-wr (whole-rock) values from 8.965 to 9.045 - almost the whole bo range. S. Mayo bo-wr data sets have standard deviations comparable to published data from other areas and appear to be geologically reasonable. The (060) peak on the IC preparates (bo-<2) was also measured, very slowly, and normal computer techniques used to deconvolute the low-intensity (060) peak. In a few cases, the illite content was too low for a peak to be determined. Surprisingly, the two methods (bo-wr &bo-<2) gave very similar results. Comparison of sample values from the two methods gives a correlation of R2= 0.93; correlation of data set means gives R2=0.96. The maximum difference between the two methods is 0.006 - ie no significant difference within error. This suggests that the detrital component had little effect on the results, but where the data sets differ, the (bo-<2) data is preferred. Thus there is no necessity to make separate preparations for the bo method, if pelitic rocks are used. R2 values for bo-wr versus (001 IC range between 0.00 and 0.93; higher R2 values (>0.7) all come from very small data sets (N<5). There seems to be no consistent, significant relationship between the two parameters.

  19. The cellular protein expression of Foxp3 in lymphoid and non-lymphoid organs of Nile tilapia.

    PubMed

    Jia, Cunxin; Zhou, Yujie; Huang, Xiaohuan; Peng, Xi; Liu, Linyan; Zhou, Linyan; Jin, Li; Shi, Hongjuan; Wei, Jing; Wang, Deshou

    2015-08-01

    In the present study, an antibody highly specific to the Nile tilapia (Oreochromis niloticus) Foxp3 was produced and characterized. Immunohistochemistry analysis indicates that Foxp3 was expressed in peripheral blood mononuclear cells (PBMC) and certain packed lymphocytes in particular, what's more, the percentage of Foxp3(+) cells among PBMC was 5.7 2.0% (n = 5) in healthy adults and could be significantly up-regulated after phytohemagglutinin (50 ?g/ml) stimulation in vitro at 6, 12 and 24 h, respectively. In the lymphoid tissues, such as the thymus, spleen and head kidney, Foxp3 expression was observed mainly in lymphocyte-like cells. Surprisingly, in the non-lymphoid organ stomach, Foxp3 was detected in epithelial-like cells within the mucosa. Our study demonstrates for the first time that Foxp3 protein expression occurs not only in hematopoietic cells of lymphoid organ systems but also non-hematopoietic cells of non-lymphoid organ in lower vertebrates such as the fish tilapia. The conserved expression pattern of Foxp3 at the protein and cellular levels implies that it might have conserved functions from fish to mammals. PMID:25804488

  20. Long term follow-up in patients with initially diagnosed low grade Ta non-muscle invasive bladder tumors: tumor recurrence and worsening progression

    PubMed Central

    2014-01-01

    Background We evaluated the clinical outcome of low grade Ta bladder cancer followed-up for a long period using the 2004 WHO grading system. Methods We retrospectively reviewed 190 patients with primary, low grade Ta bladder cancer. We defined worsening progression (WP) as confirmed high grade Ta, all T1 or Tis/concomitant CIS of bladder recurrence, upper urinary tract recurrence (UTR), or progression to equal to or more than T2. The associations between clinicopathological factors and tumor recurrence as well as WP pattern were analyzed. We also evaluated the late recurrence of 76 patients who were tumor-free for more than 5 years. Results Tumor recurrence and WP occurred in 82 (43.2%) and 21 (11.1%) patients during follow-up (median follow-up: 101.5months), respectively. WP to high grade Ta, all T1 or Tis/concomitant CIS was seen in 17 patients, and UTR and progression to equal to or more than T2 were seen in 2 and 2 patients, respectively. Multivariate analyses demonstrated that multiple tumor (p?low grade Ta bladder cancer is needed up to 10 years from the initial diagnosis. PMID:24400640

  1. GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival.

    PubMed

    Singhi, Aatur D; Davison, Jon M; Choudry, Haroon A; Pingpank, James F; Ahrendt, Steven A; Holtzman, Matthew P; Zureikat, Amer H; Zeh, Herbert J; Ramalingam, Lekshmi; Mantha, Geeta; Nikiforova, Marina; Bartlett, David L; Pai, Reetesh K

    2014-08-01

    We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis (P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms. PMID:24925222

  2. Use of a human-like low-grade bacteremia model of experimental endocarditis to study the role of Staphylococcus aureus adhesins and platelet aggregation in early endocarditis.

    PubMed

    Veloso, Tiago Rafael; Chaouch, Aziz; Roger, Thierry; Giddey, Marlyse; Vouillamoz, Jacques; Majcherczyk, Paul; Que, Yok-Ai; Rousson, Valentin; Moreillon, Philippe; Entenza, Jos Manuel

    2013-03-01

    Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles of Staphylococcus aureus surface adhesins and platelet aggregation in the infection process. In humans, however, S. aureus IE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions of S. aureus virulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 10(6) CFU of Lactococcus lactis pIL253 or a recombinant L. lactis strain expressing an individual S. aureus surface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1? (IL-1?), IL-1?, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred on L. lactis (ClfA strain) (52%; P = 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%; P < 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1? and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation of S. aureus IE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE. PMID:23250949

  3. Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis

    PubMed Central

    Veloso, Tiago Rafael; Chaouch, Aziz; Roger, Thierry; Giddey, Marlyse; Vouillamoz, Jacques; Majcherczyk, Paul; Que, Yok-Ai; Rousson, Valentin; Moreillon, Philippe

    2013-01-01

    Animal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles of Staphylococcus aureus surface adhesins and platelet aggregation in the infection process. In humans, however, S. aureus IE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions of S. aureus virulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 106 CFU of Lactococcus lactis pIL253 or a recombinant L. lactis strain expressing an individual S. aureus surface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1? (IL-1?), IL-1?, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred on L. lactis (ClfA strain) (52%; P = 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%; P < 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1? and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation of S. aureus IE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE. PMID:23250949

  4. Neutralizing Anti-IL20 Antibody Treatment Significantly Modulates Low Grade Inflammation without Affecting HbA1c in Type 2 Diabetic db/db Mice

    PubMed Central

    Mayer, Christopher; Bergholdt, Regine; Cucak, Helena; Rolin, Bidda Charlotte; Sams, Anette; Rosendahl, Alexander

    2015-01-01

    Low grade inflammation is present in pre-clinical and human type 2 diabetes. In this process, several cytokines like IL-1? and inflammatory cells like macrophages are activated and demonstrated to participate to the disease initiation and progression. IL-20 is a cytokine known to play non-redundant roles in progression of several inflammatory diseases. To address the therapeutic effect of inhibiting the IL-20 pathway in diabetes, diabetic db/db mice were treated with neutralizing anti-IL20 antibodies in vivo and both metabolic and inflammatory parameters were followed. Diabetic islets expressed the IL-20 cytokine and all IL-20 receptor components in elevated levels compared to resting non-diabetic islets. Islets were responsive to ex vivo IL-20 stimulation measured as SOCS induction and KC and IL-6 production. Neutralizing anti-IL20 treatment in vivo had no effect on HbA1c or weight although the slope of blood glucose increase was lowered. In contrast, anti-IL20 treatment significantly reduced the systemic low-grade inflammation and modulated the local pancreatic immunity. Significant reduction of the systemic IL-1? and MCP-1 was demonstrated upon anti-IL20 treatment which was orchestrated with a reduced RANTES, IL-16 and IL-2 but increased TIMP-1, MCP-1 and IL-6 protein expression locally in the pancreas. Interestingly, anti-IL20 treatment induced an expansion of the myeloid suppressor CD11bGr1int macrophage while reducing the number of CD8 T cells. Taken together, anti-IL20 treatment showed moderate effects on metabolic parameters, but significantly altered the low grade local and systemic inflammation. Hence, future combination therapies with anti-IL20 may provide beneficial therapeutic effects in type 2 diabetes through a reduction of inflammation. PMID:26162095

  5. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    SciTech Connect

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years.

  6. Inflammation-induced formation of fat-associated lymphoid clusters

    PubMed Central

    Bnzech, Ccile; Kruglov, Andrei A.; Loo, Yunhua; Nakamura, Kyoko; Zhang, Yang; Nayar, Saba; Jones, Lucy H.; Flores-Langarica, Adriana; McIntosh, Alistair; Marshall, Jennifer; Barone, Francesca; Besra, Gurdyal; Miles, Katherine; Allen, Judith E.; Gray, Mohini; Kollias, George; Cunningham, Adam F.; Withers, David R.; Toellner, Kai Michael; Jones, Nick D.; Veldhoen, Marc; Nedospasov, Sergei A.; McKenzie, Andrew N.J.; Caamao, Jorge H.

    2015-01-01

    Fat-associated lymphoid clusters (FALCs) are a recently discovered type of lymphoid tissue associated with visceral fat. Here we show that distribution of FALCs was heterogeneous with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 B cells in the peritoneal cavity through high expression of the chemokine CXCL13 and supported B cell proliferation and germinal center differentiation during peritoneal immune challenges. FALC formation was induced by inflammation, which triggered recruitment of myeloid cells that express tumor necrosis factor (TNF) necessary for TNF receptor-signaling in stromal cells. CD1d-restricted Natural killer T (NKT) cells were likewise required for inducible formation of FALCs. Thus, FALCs support and coordinate innate B and T cell activation during serosal immune responses. PMID:26147686

  7. Coexistent orbital dermatofibrosarcoma protuberans and bilateral lymphoid hyperplasia.

    PubMed

    Gonnering, R S; Sonneland, P R

    1987-01-01

    A 72-year-old man had secondary orbital involvement with dermatofibrosarcoma protuberans 36 years after removal of the initial tumor on his forehead. In addition, multiple bilateral inferior orbital masses were present, which on pathologic examination proved to be reactive lymphoid hyperplasia. Serum immunoelectrophoresis revealed polyclonal elevations of IgG and IgA. Dermatofibrosarcoma protuberans is part of the spectrum of fibrohistiocytic tumors that also includes atypical fibroxanthoma and benign and malignant fibrous histiocytoma. The exact cell of origin of dermatofibrosarcoma protuberans is controversial, though immunohistochemical study of our specimen supports the fibroblast. The coexistence of this rare orbital tumor with noncontiguous reactive lymphoid hyperplasia is unique, and points out the fact that multiple orbital masses may indicate more than one underlying disease process. PMID:3154572

  8. Beyond NK cells: the expanding universe of innate lymphoid cells.

    PubMed

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658

  9. Immunosuppression and organ transplantation tolerance using total lymphoid irradiation

    SciTech Connect

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1980-01-01

    Total lymphoid irradiation (TLI) is a method which delivers irradiation daily in fractionated doses (200 rads) to lymphoid organs while shielding bones, lungs, and the majority of the gastrointestinal tract. TLI is lymphocytopenic in mice, rats, dogs, and humans, and both T cells and B cells are eliminated from the circulation. TLI permits establishment of specific and long-lasting tolerance to alloantigens. Permanent acceptance of allogeneic bone marrow cells without graft-versus-host disease was achieved in rats and dogs across major histocompatibility barriers. Recipients were tolerant to allografts of skin, hearts, and kidney from animals syngeneic to marrow donors or to organs from the marrow donor. This approach may be suitable for pancreas transplantation in diabetes.

  10. Treatment of intractable rheumatoid arthritis with lymphoid irradiation

    SciTech Connect

    Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.

    1981-01-01

    Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

  11. Pseudolymphoma (reactive lymphoid hyperplasia) of the liver: A clinical challenge

    PubMed Central

    Kwon, Yong Kyong; Jha, Reena C; Etesami, Kambiz; Fishbein, Thomas M; Ozdemirli, Metin; Desai, Chirag S

    2015-01-01

    Reactive lymphoid hyperplasia (RLH), also known as pseudolymphoma or nodular lymphoid lesion of the liver is an extremely rare condition, and only 51 hepatic RLH cases have been described in the literature since the first case was described in 1981. The majority of these cases were asymptomatic and incidentally found through radiological imaging. The precise etiology of hepatic RLH is still unknown, but relative high prevalence of autoimmune disorder in these cases suggests an immune-based liver disorder. Imaging features of hepatic RLH often suggest malignant lesions such as hepatocellular carcinoma and cholangiocarcinoma. In this report, we discuss two cases of hepatic RLH in patients with autoimmune hepatitis. We also present pathologic and magnetic resonance imaging findings, including one case utilizing a hepatocellular contrast agent, Eovist. Definitive diagnosis of hepatic RLH often requires surgical excision. PMID:26609347

  12. Beyond NK Cells: The Expanding Universe of Innate Lymphoid Cells

    PubMed Central

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658

  13. Total lymphoid irradiation in refractory systemic lupus erythematosus

    SciTech Connect

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-07-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

  14. Gammadelta T cells and the lymphoid stress-surveillance response.

    PubMed

    Hayday, Adrian C

    2009-08-21

    The investigation of gammadelta T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downstream, adaptive immunity. Recent studies have identified striking mechanisms by which gammadelta cells meet the requirements of stress surveillance. For example, high response frequencies can reflect a unique nature of antigen engagement by the T cell receptor (TCR), developmental focusing of the repertoire by selection events, or the use of nonclonotypic receptors to initiate responses. Likewise, rapid functional deployment can be facilitated by the preprogramming of gammadelta cells during development. Additionally, gammadelta cells can directly influence adaptive immunity by functioning as antigen-presenting cells. With lymphoid stress surveillance likely to underpin numerous aspects of inflammation, tumor immunology, infectious disease, and autoimmunity, this perspective considers its properties and its emerging potential for clinical manipulation. PMID:19699170

  15. Treatment of refractory chronic demyelinating polyneuropathy with lymphoid irradiation

    SciTech Connect

    Rosenberg, N.L.; Lacy, J.R.; Kennaugh, R.C.; Holers, V.M.; Neville, H.E.; Kotzin, B.L.

    1985-03-01

    Four patients with refractory or poorly responsive chronic progressive demyelinating polyneuropathy (CPDP) were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study. All patients had previously failed conventional therapy for CPDP, as well as other unconventional treatments. During a follow-up period of 7 to 12 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 to Leu-3 T cells in the blood. Three of the four patients demonstrated improvement in distal muscle strength, and this was associated with increased functional capabilities in two patients. In contrast, no clinical improvement in sensation was noted in any patient. Nerve conduction studies showed patchy improvement in three patients. The results of this preliminary uncontrolled study indicate that radiotherapy deserves further study in the treatment of CPDP.

  16. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    SciTech Connect

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-05-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.

  17. Cellular mechanisms of tolerance after total lymphoid irradiation (TLI)

    SciTech Connect

    Strober, S.; King, D.P.; Gottlieb, M.S.; Hoppe, R.T.; Kaplan, H.S.

    1981-03-01

    In this review article on the cellular mechanisms of tolerance after total lymphoid irradiation (TLI), the effect of radiation dose and time of bone marrow infusion in mice are studied. TLI is compared to whole body irradiation with respect to the development of graft-host reaction and the number of stable chimeras obtained. The relationship between nonspecific suppressor cells and the development of tolerance after TLI is discussed. (KRM)

  18. Evidence that somatostatin is localized and synthesized in lymphoid organs

    SciTech Connect

    Aguila, M.C.; McCann, S.M. ); Dees, W.L.; Haensly, W.E. )

    1991-12-15

    Because several peptides originally found in the pituitary as within the central nervous system have been localized in lymphoid tissues and because somatostatin (somatotropin-release-inhibiting hormone, SRIH) can act on cells of the immune system, the authors searched for this peptide in lymphoid organs. The authors demonstrated that SRIH mRNA exists in lymphoid tissue, albeit in smaller levels that in the periventricular region of the hypothalamus, the brain region that contains the highest level of this mRNA. SRIH mRNA was found in the spleen and thymus of male rats and in the spleen, thymus, and bursa of Fabricius of the chicken. Its localization in the Bursa indicates that the peptide must be present in B lymphocytes since this is the site of origin of B lymphocytes in birds. The SRIH concentration in these lymphoid organs as determined by radioimmunoassay was greater in the thymus than in the spleen of the rat. Fluorescence immunocytochemistry revealed the presence of SRIH-positive cells in clusters inside the white pulp and more dispersed within the red pulp of the spleen of both the rat and the chicken. The thymus from these species also contained SRIH-positive cells within the medulla and around the corticomedullary junction. In the chicken, there were large cluster of SRIH-positive cells in the medullary portion of each nodule of the bursa of Fabricius. The results indicate that SRIH is synthesized and stored in cells of the immune system. SRIH may be secreted from these cells to exert paracrine actions that alter the function of immune cells in spleen and thymus.

  19. Identification of a novel lymphoid population in the murine epidermis

    PubMed Central

    Almeida, Francisca F.; Tenno, Mari; Brzostek, Joanna; Li, Jackson LiangYao; Allies, Gabriele; Hoeffel, Guillaume; See, Peter; Ng, Lai Guan; Fehling, Hans Jrg; Gascoigne, Nicholas R. J.; Taniuchi, Ichiro; Ginhoux, Florent

    2015-01-01

    T cell progenitors are known to arise from the foetal liver in embryos and the bone marrow in adults; however different studies have shown that a pool of T cell progenitors may also exist in the periphery. Here, we identified a lymphoid population resembling peripheral T cell progenitors which transiently seed the epidermis during late embryogenesis in both wild-type and T cell-deficient mice. We named these cells ELCs (Epidermal Lymphoid Cells). ELCs expressed Thy1 and CD2, but lacked CD3 and TCR??/?? at their surface, reminiscent of the phenotype of extra- or intra- thymic T cell progenitors. Similarly to Dendritic Epidermal T Cells (DETCs), ELCs were radioresistant and capable of self-renewal. However, despite their progenitor-like phenotype and expression of T cell lineage markers within the population, ELCs did not differentiate into conventional T cells or DETCs in in vitro, ex vivo or in vivo differentiation assays. Finally, we show that ELC expressed NK markers and secreted IFN-? upon stimulation. Therefore we report the discovery of a unique population of lymphoid cells within the murine epidermis that appears related to NK cells with as-yet-unidentified functions. PMID:26223192

  20. Treatment of intractable lupus nephritis with total lymphoid irradiation

    SciTech Connect

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-04-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.

  1. [Interstitial lymphoid pneumonia associated with common variable immunodeficiency].

    PubMed

    Peralta, Gonzalo; Villagomez, Renzo; Bosio, Martin; Quadrelli, Silvia; Chertcoff, Julio; Vigovich, Flix

    2011-01-01

    The interstitial lymphoid pneumonia (LIP) is an uncommon disorder, described as non-neoplastic lung lymphoid tissue hyperplasia and classified as an interstitial lung disease. It has been described in association with HIV infection, autoimmune disorders, policlonal hypergammaglobulinemia and less frequently, with hypogammaglobulinemia. We report the case of a 66 year old female patient with a history of diabetes, Sjogren syndrome and hypertension. She was referred to our hospital due to a dry cough and dyspnea (FC II-III). The physical examination showed bilateral dry crackles and splenomegaly. Laboratory studies showed thrombocytopenia (50 000/ mm3) and hypogammaglobulinemia. A computed tomography thoracic scan showed interstitial bilateral basal lung infiltrates with small peribroncovascular nodules. A lung biopsy was made by thoracoscopy and reported LIP. Initial treatment consisted of oral methilprednisone, 40 mg daily, and once a month intravenous gammaglobulin 500 mg/kg, with good clinical and radiological response. A splenectomy was done due to persistent thrombocytopenia associated with hypersplenism, with good response of the platelets counts. No lymphoid clonal or other associated disease was detected. PMID:22057175

  2. Spiradenocarcinoma with low-grade basal cell adenocarcinoma pattern: report of a case with varied morphology and wild type TP53.

    PubMed

    Petersson, Fredrik; Nga, Min En

    2012-03-01

    We present a patient with a 2-cm spiradenocarcinoma of the left arm resembling low-grade salivary gland basal cell adenocarcinoma. In addition to showing attributes of conventional spiradenoma, the benign component showed prominent areas of cystic change with focal apocrine differentiation, glands with and without mucinous differentiation, clear cell change and focal adenoid cystic carcinoma-like areas. The malignant component was composed of nodules of basaloid cells arranged in sheets with variable tendency to luminal differentiation. The nuclear atypia was low-grade, and the mitotic index was high in the malignant component (to 8/10 high power fields). Immunohistochemically, there was diffuse but variable positivity for cytokeratin 7 in both the benign and malignant components. Epithelial membrane antigen was focally positive, highlighting cells with ductal (luminal) differentiation. Expression of p63 was observed in 50 and 80% of the cells in the benign and malignant components, respectively. Calponin was negative. The proliferative index (MIB-1/Ki-67) was <3% in the benign component and up to 10% in the malignant component. Although the malignant component displayed patchy areas with nuclear p53 immunoreactivity with variable intensity, no mutation in the TP53 gene was identified. PMID:22077486

  3. Expression of E6, p53 and p21 proteins and physical state of HPV16 in cervical cytologies with and without low grade lesions

    PubMed Central

    Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar del Moral; Romero, Luz del Carmen Alarcón

    2014-01-01

    The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker. PMID:24482706

  4. Serum IL-12 Is Increased in Mexican Obese Subjects and Associated with Low-Grade Inflammation and Obesity-Related Parameters

    PubMed Central

    Surez-lvarez, K.; Sols-Lozano, L.; Leon-Cabrera, S.; Gonzlez-Chvez, A.; Gmez-Hernndez, G.; Quiones-lvarez, M. S.; Serralde-Ziga, A. E.; Hernndez-Ruiz, J.; Ramrez-Velsquez, J.; Galindo-Gonzlez, F. J.; Zavala-Castillo, J. C.; De Len-Nava, M. A.; Robles-Daz, G.; Escobedo, G.

    2013-01-01

    Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF-?), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF-? (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans. PMID:23533314

  5. Detection of numerical and structural alterations and fusion of chromosomes 16 and 1 in low-grade papillary breast carcinoma by fluorescence in situ hybridization.

    PubMed Central

    Tsuda, H.; Takarabe, T.; Susumu, N.; Inazawa, J.; Okada, S.; Hirohashi, S.

    1997-01-01

    Intracystic papillary breast tumors, including intraductal papilloma and low-grade intracystic papillary carcinoma, constitute a group for which differential diagnosis is frequently difficult. We examined the status of chromosomes 16 and 1 by multicolor fluorescence in situ hybridization (FISH) analyses and the DNA ploidy patterns by flow cytometry in 26 intracystic papillary tumors. Alterations of chromosomes 16 and 1 were detected by FISH in 93 and 85%, respectively, of 14 low-grade papillary carcinomas, and the latter alterations always concurred with the former. Two-color FISH using probes for the D1Z1 (1q12) and D16Z2 (16cen) loci or the D1Z1 and D16Z3 (16q11) loci showed that fusion of chromosomes 16 and 1, mostly with breakpoints distal to 16q11.2 and proximal to 1q12, occurred in 77% of the papillary carcinomas. DNA aneuploidy was detected in 6% of these carcinomas. No papilloma showed these chromosome alterations or DNA aneuploidy. Chromosome 16 and 1 fusions appeared to occur frequently in diploid breast carcinomas and to be involved in the acquisition of a malignant phenotype by duct epithelial cells. We suggest that two-color FISH methods for detecting 1;16 fusions might be applicable as supportive methods for the differential diagnosis of intracystic papillary breast tumors. Images Figure 1 Figure 2 PMID:9327736

  6. Transthoracic fine-needle aspiration cytology of non-invasive, low-grade urothelial carcinoma with lung metastasis: A case report with review of the literature

    PubMed Central

    Vural, i?dem; Yildiz, Krsat; abuk, Devrim; Akgl, Asli

    2015-01-01

    Radiological analyses in a 61-year-old patient being followed since 2005 for low-grade, non-invasive urothelial carcinoma (UC) (Ta) revealed a 5-cm pleural-based mass in the lower lobe of the right lung for which a subsequent transthoracic fine-needle aspiration cytology was performed. Upon observing the carcinoma cells consistent with UC metastasis, systemic chemotherapy was commenced. The patient underwent a metastatectomy based on the thoracic computerized tomography scan performed on the 4th month of treatment, which revealed notable regression. The resected tumor was morphologically similar to cells seen in the transthoracic fine-needle aspiration and was immunohistochemically positive for p63, uroplakin, thrombomodulin, CK7 and CK20 at varying degrees but was negative for TTF-1. We report a case of metastatic UC of the lung in a patient who had had a low-grade superficial UC of the urinary bladder and we discuss the cytopathological features of this rare entity in light of the literature. PMID:26229254

  7. Cell cycle and apoptosis regulatory proteins, proliferative markers, cell signaling molecules, CD209, and decorin immunoreactivity in low-grade myxofibrosarcoma and myxoma.

    PubMed

    Cates, Justin M M; Memoli, Vincent A; Gonzalez, Raul S

    2015-08-01

    The histologic differential diagnosis between intramuscular myxoma and low-grade myxofibrosarcoma can be quite difficult in some cases. To identify a diagnostic immunohistochemical marker, we compared the staining profiles of 19 different antigens, including cell cycle proteins, apoptosis proteins, and proliferative markers, and selected other signaling and structural proteins in these two tumors. Ten cases each of intramuscular myxoma and low-grade myxofibrosarcoma were stained with antibodies directed against apoptosis regulatory proteins (Bcl2, activated caspase-3, phospho-H2A.X, and cleaved PARP), cell cycle regulatory proteins (Rb1, Cyclin-A, CDKN1B, and Cdt1), proliferative markers (KI67, MCM2, phospho-histone H3, and geminin), cell signalling molecules (c-Myc, EGF, EGFR, PLA2G4A, and HSP90), a dendritic cell marker (CD209), and the extracellular matrix proteoglycan decorin. Staining patterns of myxoma and myxofibrosarcoma were compared using Fisher's exact test and the Mann-Whitney test. For each potential diagnostic marker studied, the proportions of cases scored as positive on both dichotomous or ordinal scales were not significantly different between myxoma and myxofibrosarcoma. Myxoma and myxofibrosarcoma share a common immunophenotype for each of the markers studied. Distinction between these tumors is still predominantly based on morphologic criteria. PMID:25940995

  8. Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: evidence for intergenerational effects of low grade inflammation

    PubMed Central

    Kuzawa, Christopher W.; Tallman, Paula S.; Adair, Linda S.; Lee, Nanette; McDade, Thomas W.

    2012-01-01

    Background Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. Aim Evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Subjects and methods Data come from 234 parous Filipino females (21.5 0.3 yr) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1?), tumor necrosis factor alpha (TNF?), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. Results BW in female offspring was lower only among women with high IL-1?. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p<0.104) gave birth to the largest males. Conclusion Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential intergenerational effects of chronic low-grade inflammation. PMID:22690728

  9. Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

    PubMed Central

    Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Menendez, Javier A.; Vazquez-Martin, Alejandro; Sirvent, Juan J.; Martín-Paredero, Vicente; Corbí, Angel L.; Sierra-Filardi, Elena; Aragonès, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge

    2013-01-01

    Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study. PMID:24453432

  10. [A case of stump MALT lymphoma after partial gastrectomy].

    PubMed

    Choi, Sun Young; Lee, Joung Il; Noh, Tae June; Jang, Jae Young; Nam, Ki Deuk; Kim, Nam Hoon; Lee, Sang Kil; Joo, Kwang Ro; Dong, Seok Ho; Kim, Hyo Jong; Kim, Byung Ho; Chang, Young Woon; Chang, Rin

    2006-05-01

    Gastrectomy is known to be a risk factor for adenocarcinoma in remnant stomach. It is suggested that reflux of bile juice or duodenal secretion to remnant stomach induces atrophic gastritis, intestinal metaplasia, and gastric adenocarcinoma. Malignant lymphoma in remnant stomach after gastrectomy is very rare. Only about thirty cases are reported in the world, and there is no case report in Korea. Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is associated with Helicobacter pylori infection but the mechanism of lymphoma development in remnant stomach is still unknown. We report a case of low grade gastric MALT lymphoma of gastric stump after 10 years from partial gastrectomy. PMID:16714883

  11. Primary B-cell malignant lymphoma of the lung.

    PubMed

    Canver, C C

    1993-10-01

    A 52-year-old asymptomatic man was evaluated for two right lung lesions discovered on a chest roentgenogram during a routine physical examination. A computed tomographic scan revealed the absence of mediastinal nodal involvement. Guided-needle aspiration cytology was inconclusive. A subsequent right thoracotomy was necessary to perform biopsy of these masses, which proved to be B-cell malignant lymphomas of the lung. This case represents a rare example of a primary low-grade B-cell pulmonary lymphoma of mucosa-associated lymphoid tissue, with its distinct clinicopathologic features. PMID:8215676

  12. Ectopic lymphoid follicles: inducible centres for generating antigen-specific immune responses within tissues.

    PubMed

    Jones, Gareth W; Jones, Simon A

    2016-02-01

    Lymphoid neogenesis is traditionally viewed as a pre-programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen-specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto-immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease. PMID:26551738

  13. Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

    SciTech Connect

    Jalali, Rakesh . E-mail: rjalali@medscape.com; Goswami, Savita; Sarin, Rajiv; More, Niteen; Siddha, Manish; Kamble, Rashmi

    2006-11-15

    Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in patients >16 years old was 23 at baseline and had improved to 17 and 14 at the 6-month and 24-month follow-up assessments, respectively. Conclusion: Our data demonstrated neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT, however, did not result in any additional worsening. These encouraging results need to be validated in a study with a larger number of patients and longer follow-up.

  14. Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma

    PubMed Central

    Sie, Mariska; den Dunnen, Wilfred F. A.; Lourens, Harm Jan; Meeuwsen-de Boer, Tiny G. J.; Scherpen, Frank J. G.; Zomerman, Walderik W.; Kampen, Kim R.; Hoving, Eelco W.; de Bont, Eveline S. J. M.

    2015-01-01

    Up to now, several clinical studies have been started investigating the relevance of receptor tyrosine kinase (RTK) inhibitors upon progression free survival in various pediatric brain tumors. However, single targeted kinase inhibition failed, possibly due to tumor resistance mechanisms. The present study will extend our previous observations that vascular endothelial growth factor receptor (VEGFR)-2, platelet derived growth factor receptor (PDGFR)β, Src, the epidermal growth factor receptor (ErbB) family, and hepatocyte growth factor receptor (HGFR/cMet) are potentially drugable targets in pediatric low grade astrocytoma and ependymoma with investigations concerning growth-factor-driven rescue. This was investigated in pediatric low grade astrocytoma and ependymoma cell lines treated with receptor tyrosine kinase (RTK) inhibitors e.g. sorafenib, dasatinib, canertinib and crizotinib. Flow cytometry analyses showed high percentage of cells expressing VEGFR-1, fibroblast growth factor receptor (FGFR)-1, ErbB1/EGFR, HGFR and recepteur d’origine nantais (RON) (respectively 52-77%, 34-51%, 63-90%, 83-98%, 65-95%). Their respective inhibitors induced decrease of cell viability, measured with WST-1 cell viability assays. At least this was partially due to increased apoptotic levels measured by Annexin V/Propidium Iodide apoptosis assays. EGF, HGF and FGF, which are normally expressed in brain (tumor) tissue, showed to be effective rescue inducing growth factors resulting in increased cell survival especially during treatment with dasatinib (complete rescue) or sorafenib (partial rescue). Growth-factor-driven rescue was less prominent when canertinib or crizotinib were used. Rescue was underscored by significantly activating downstream Akt and/or Erk phosphorylation and increased tumor cell migration. Combination treatment showed to be able to overcome the growth-factor-driven rescue. In conclusion, our study highlights the extensive importance of environmentally present growth factors in developing tumor escape towards RTK inhibitors in pediatric low grade astrocytoma and ependymoma. It is of great interest to anticipate upon these results for the design of new therapeutic trials with RTK inhibitors in these pediatric brain tumors. PMID:25799134

  15. Skin-associated lymphoid tissues (SALT): origins and functions

    SciTech Connect

    Streilein, J.W.

    1983-06-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT.

  16. Gallium scanning in lymphoid interstitial pneumonitis of children with AIDS

    SciTech Connect

    Schiff, R.G.; Kabat, L.; Kamani, N.

    1987-12-01

    Lymphoid interstitial pneumonitis (LIP) is a frequent pulmonary complication in the child with the acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. We report the gallium scan findings in two children with AIDS and LIP. Gallium scintigraphy in both children demonstrated increased radionuclide concentration throughout the lungs, a pattern indistinguishable scintigraphically from that of Pneumocystis carinii pneumonia (PCP). This should alert nuclear medicine practitioners and referring physicians to another cause of diffusely increased gallium uptake in the lungs of patients with AIDS.

  17. Women in a region with high incidence of cervical cancer warrant immediate colposcopy for low-grade squamous intraepithelial lesion on cervical cytology.

    PubMed

    Phongnarisorn, C; Srisomboon, J; Siriaungkul, S; Khunamornpong, S; Suprasert, P; Charoenkwan, K; Cheewakriangkrai, C; Siriaree, S; Saphan, K

    2006-01-01

    The objective of this study was to determine the prevalence of high-grade histologic diagnoses in women who had low-grade squamous intraepithelial lesion (LSIL) on Pap smear in an area with high incidence of cervical cancer. We conducted a retrospective study of 220 women with LSIL cytology undergoing colposcopic examination in Chiang Mai University Hospital between January 1999 and July 2004. The histologic diagnoses, obtained from colposcopically directed biopsy or electrical loop excision after initial colposcopy, showed that 80 (36.4%) women had histologically confirmed high-grade lesions and 11 (5%) women had microinvasive (9) and frankly invasive (2) carcinomas. Overall, 41.5% of women with LSIL on Pap smear had significant underlying lesions, requiring appropriate treatment. In conclusion, in the region with high incidence of cervical cancer, women with LSIL cytology are at increased risk of having underlying high-grade lesions and invasive cancer. Immediate referral for colposcopy is warranted. PMID:16884366

  18. 40Ar/39Ar Data for White Mica, Biotite, and K-Feldspar Samples from Low-Grade Metamorphic Rocks in the Westminster Terrane and Adjacent Rocks, Maryland

    USGS Publications Warehouse

    Kunk, Michael J.; McAleer, Ryan

    2008-01-01

    This report contains reduced 40Ar/39Ar data of white mica and K-feldspar mineral separates and matrix of a whole rock phyllite, all from low-grade metamorphic rocks of the Westminster terrane and adjacent strata in central Maryland. This report presents these data in a preliminary form, but in more detail than can be accommodated in todays professional journals. Also included in this report is information on the location of the samples and a brief description of the samples. The data contained herein are not interpreted in a geological context, and care should be taken by readers unfamiliar with argon isotopic data in the use of these results; many of the individual apparent ages are not geologically meaningful. This report is primarily a detailed source document for subsequent publications that will integrate these data into a geological context.

  19. Low Grade Micropapillary Urothelial Carcinoma, Does It Exist? - Analysis of Management and Outcomes from the Surveillance, Epidemiology and End Results (SEER) Database

    PubMed Central

    Vourganti, Srinivas; Harbin, Andrew; Singer, Eric A.; Shuch, Brian; Metwalli, Adam R.; Agarwal, Piyush K.

    2013-01-01

    Objective: To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology. Methods: All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes. Results: From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%). Conclusion: Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases. PMID:23678370

  20. Comparison between Instrumented Mini-TLIF and Instrumented Circumferential Fusion in Adult Low-Grade Lytic Spondylolisthesis : Can Mini-TLIF with PPF Replace Circumferential Fusion?

    PubMed Central

    Kim, Dong-Hyun; Lee, Sang-Ho

    2009-01-01

    Objective To evaluate clinical and radiological results of two different fusion techniques in adult low-grade isthmic spondylolisthesis. Methods Between November 2003 and December 2004, 46 consecutive patients underwent instrumented mini-transforaminal lumbar interbody fusion (mini-TLIF) (group I) at Wooridul Spine Hospital, Seoul, Korea. Between February 2003 and October 2006, 32 consecutive patients underwent instrumented circumferential fusion (group II) at Leon Wiltse Memorial Hospital, Suwon, Korea. The mean follow-up periods were 29.7 and 26.1 months, respectively. Results Mean visual analog scale (VAS) scores for back and leg pain decreased, respectively, from 6.98 and 6.33 to 2.3 and 2.2 in group I and from 7.38 and 6.00 to 1.7 and 1.0 in group II. Mean Oswestry disability index (ODI) improved from 51.85% to 14.4% in group I and from 60% to 9.1% in group II. In both groups, VAS and ODI scores significantly changed from pre- to postoperatively (p<0.001), but postoperative outcome between groups was statistically not significant. Radiologic evidence of fusion was noted in 95.7% and 100% of the patients in group I and II, respectively. In both groups, changes in disc height, segmental lordosis, degree of listhesis, and whole lumbar lordosis between the pre- and postoperative periods were significant except whole lumbar lordosis in both groups. Conclusion Clinical and functional outcomes demonstrate no significant differences between groups in treating back and leg pain of adult patients with low-grade isthmic spondylolisthesis. However, in terms of operative data (i.e. operation time and hospital stay), instrumented mini-TLIF demonstrated better results. PMID:19274115

  1. Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse

    PubMed Central

    Gao, Helen G. L.; Fisher, Paul W.; Lambi, Alex G.; Wade, Christine K.; Barr-Gillespie, Ann E.; Popoff, Steven N.; Barbe, Mary F.

    2013-01-01

    We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed. PMID:24015193

  2. Low grade radiographic sacroiliitis as prognostic factor in patients with undifferentiated spondyloarthritis fulfilling diagnostic criteria for ankylosing spondylitis throughout follow up

    PubMed Central

    Huerta?Sil, G; Casasola?Vargas, J C; Londoo, J D; Rivas?Ruz, R; Chvez, J; Pacheco?Tena, C; Cardiel, M H; Vargas?Alarcn, G; Burgos?Vargas, R

    2006-01-01

    Objective To determine the rate and factors associated with ankylosing spondylitis in a cohort of patients with undifferentiated spondyloarthritides (SpA). Methods 62 consecutive patients with undifferentiated SpA seen between 1998 and 1999 underwent clinical and imaging evaluations throughout follow up. The main outcome measure was a diagnosis of ankylosing spondylitis. Results 50 patients with peripheral arthritis (n?=?35) and inflammatory back pain (n?=?24) (26 male; mean (SD) age at onset, 20.4 (8.8) years; disease duration 5.4 (5.7) years) were followed up for 35 years. At baseline, >90% of patients had axial and peripheral disease, while 38% had radiographic sacroiliitis below the cut off level for a diagnosis of ankylosing spondylitis (BASDAI 3.9, BASFI 2.9). At the most recent evaluation, 21 patients (42%) had ankylosing spondylitis. Two factors were associated with a diagnosis of ankylosing spondylitis in multivariate analysis: radiographic sacroiliitis grade <2 bilateral, or grade <3 unilateral (odds ratio (OR)?=?11.18 (95% confidence interval, 2.59 to 48.16), p?=?0.001), particularly grade 1 bilateral (OR?=?12.58 (1.33 to 119.09), p?=?0.027), and previous uveitis (OR?=?19.25 (1.72 to 214.39), p?=?0.001). Acute phase reactant levels, juvenile onset, and HLA?B27 showed a trend to linkage with ankylosing spondylitis (NS). Conclusions Low grade radiographic sacroiliitis is a prognostic factor for ankylosing spondylitis in patients originally classified as having undifferentiated SpA. Low grade radiographic sacroiliitis should be regarded as indicative of early ankylosing spondylitis in patients with undifferentiated SpA. PMID:16219705

  3. Association between Low-Grade Albuminuria and Cardiovascular Risk in Korean Adults: The 20112012 Korea National Health and Nutrition Examination Survey

    PubMed Central

    Hong, Jae Won; Ku, Cheol Ryong; Noh, Jung Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Dong-Jun

    2015-01-01

    Background Recent studies have indicated that low UACR levels (<30 ?g/mg) previously considered to be in the normal range (low-grade albuminuria) are associated with cardiovascular morbidity and mortality in the general population. Methods We studied 9,736 participants with albuminuria in the normal range from the 20112012 Korea National Health and Nutrition Examination Survey (KNHANES). Results The weighted prevalences of metabolic syndrome (MS) and the 10-year risk for coronary heart disease measured using the Framingham risk score (FRS) ? 20% (high risk) were 22.5 0.7% and 14.5 0.7%, respectively, in males and 23.3 0.8% and 8.5 0.4%, respectively in females. Weighted comparisons among the tertiles of UACR revealed that the prevalences of MS and high-risk FRS increa