High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway

PubMed Central

Wu, Hao; Liu, Yunyun; Wang, Hongkun; Xu, Xianming

2015-01-01

Objective: To explore the changes in pancreas islet function of pregnant rats after consumption of high-fat diet and the underlying mechanism. Methods: Thirty pregnant Wistar rats were randomly divided into two groups: high-fat diet group and normal control group. Twenty days after gestation, fasting blood glucose concentration (FBG) and fasting serum insulin concentration (FINS) were measured. Then, oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed. Finally, all the rats were sacrificed and pancreas were harvested. Insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues. Results: The body weight was significantly increased in the high-fat diet group compared with that of normal control rats (P<0.05). The fasting plasma glucose of rats in high-fat diet group was significantly increased compared with that of normal control rats (6.62 mmol/L vs. 4.96 mmol/L, P<0.05), however there was no significant difference in fasting serum insulin concentration between the two groups. OGTT and IRT were abnormal in the high-fat diet group. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and glucose transporter 2 (Glut2) were decreased significantly compared with those of normal control group. Conclusion: High-fat diet feeding during pregnancy may induce insulin resistance in maternal rats by inhibiting pancreatic Pax6 and its target genes expression. PMID:26191217

Sequential and combinatorial roles of maf family genes define proper lens development.

PubMed

Reza, Hasan Mahmud; Urano, Atsuyo; Shimada, Naoko; Yasuda, Kunio

2007-01-16

Maf proteins have been shown to play pivotal roles in lens development in vertebrates. The developing chick lens expresses at least three large Maf proteins. However, the transcriptional relationship among the three large maf genes and their various roles in transactivating the downstream genes largely remain to be elucidated. Chick embryos were electroporated with wild-type L-maf, c-maf, and mafB by in ovo electroporation, and their effects on gene expression were determined by in situ hybridization using specific probes or by immunostaining. Endogenous gene expression was determined using nonelectroporated samples. A regulation mechanism exists among the members of maf family gene. An early-expressed member of this gene family typically stimulates the expression of later-expressed members. We also examined the regulation of various lens-expressing genes with a focus on the interaction between different Maf proteins. We found that the transcriptional ability of Maf proteins varies, even when the target is the same, in parallel with their discrete functions. L-Maf and c-Maf have no effect on E-cadherin expression, whereas MafB enhances its expression and thereby impedes lens vesicle formation. This study also revealed that Maf proteins can regulate the expression of gap junction genes, connexins, and their interacting partner, major intrinsic protein (MIP), during lens development. Misexpression of L-Maf and c-Maf induces ectopic expression of Cx43 and MIP; in contrast, MafB appears to have no effect on Cx43, but induces MIP significantly as evidenced from our gain-of-function experiments. Our results indicate that large Maf function is indispensable for chick lens initiation and development. In addition, L-Maf positively regulates most of the essential genes in this program and directs a series of molecular events leading to proper formation of the lens.

Fibrosarcoma of the nose and the paranasal sinuses.

PubMed

Olekszyk, J; Siliunas, V; Mauer, T; Biondi, R

1989-07-01

We report a case of fibrosarcoma of the nose and paranasal sinuses and give a brief review of the literature. Fibrosarcoma of the nose and paranasal sinuses is uncommon, and few cases have been reported to date. Previously these tumors may have been overdiagnosed secondary to inadequate diagnostic procedures. Because histologic diagnosis is difficult, these tumors have been confused with other lesions of the head and neck. Thus, the improvement in diagnostic procedures has significantly reduced the reported incidence of fibrosarcoma. Because histologic diagnosis is difficult, this tumor has often been confused with other lesions of the head and neck. To ensure proper handling of the tissue, the pathologist should be informed if fibrosarcoma is suspected. It may be necessary to use electron microscopy or staining techniques such as immunoperoxidase stains to distinguish fibrosarcoma from other lesions. Unfortunately, the early signs and symptoms of the tumor are vague and sometimes misleading. Thus, at the patient's initial visit, it is important that the physician consider the possibility of fibrosarcoma.

Clinical experience of integrative cancer immunotherapy with GcMAF.

PubMed

Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Hori, Hitoshi; Sakamoto, Norihiro

2013-07-01

Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

Intra Oral Fibrosarcoma with Various Histopathological Patterns: A Rare Case Report

PubMed Central

Reddy, A. Vikram Simha; Prakash, A. Ravi; Ram, V. Sai; Thorati, Rukmini Swathi

2015-01-01

Fibrosarcoma has been defined as a malignant mesenchymal tumour, the cells of which recapitulate the appearance of the normal fibroblast, with variable collagen production. Fibrosarcoma is a very uncommon tumour in the head and neck regions constituting only 0.05% of all the fibrosarcomas presenting in humans. They cause no characteristic symptoms and pose difficulty in clinical diagnosis. They have been classified histologically based on their distinct features into myxoid fibrosarcoma, low grade fibromyxoid fibrosarcoma and sclerosing epitheloid sarcoma. Here we present a rare case report of a 45-year-old male patient presenting with a maxillary fibrosarcoma, which histologically presented with different patterns. PMID:26393135

A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Xun; Guanga, Gerald P; Wan, Cheng

2012-11-13

MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic β-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA–DNA complex. MafA forms base-specific hydrogen bonds with the flanking G –5C –4 andmore » central C 0/G 0 bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse–chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.« less

Alpinia officinarum Stimulates Osteoblast Mineralization and Inhibits Osteoclast Differentiation.

PubMed

Shim, Ki-Shuk; Lee, Chung-Jo; Yim, Nam-Hui; Gu, Min Jung; Ma, Jin Yeul

2016-01-01

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton's tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

The recombinant expression and activity detection of MAF-1 fusion protein.

PubMed

Fu, Ping; Wu, Jianwei; Gao, Song; Guo, Guo; Zhang, Yong; Liu, Jian

2015-10-01

This study establishes the recombinant expression system of MAF-1 (Musca domestica antifungal peptide-1) and demonstrates the antifungal activity of the expression product and shows the relationship between biological activity and structure. The gene segments on mature peptide part of MAF-1 were cloned, based on the primers designed according to the cDNA sequence of MAF-1. We constructed the recombinant prokaryotic expression plasmid using prokaryotic expression vector (pET-28a(+)) and converted it to the competent cell of BL21(DE3) to gain recombinant MAF-1 fusion protein with His tag sequence through purifying affinity chromatographic column of Ni-NTA. To conduct the Western Blotting test, recombinant MAF-1 fusion protein was used to produce the polyclonal antibody of rat. The antifungal activity of the expression product was detected using Candida albicans (ATCC10231) as the indicator. The MAF-1 recombinant fusion protein was purified to exhibit obvious antifungal activity, which lays the foundation for the further study of MAF-1 biological activity, the relationship between structure and function, as well as control of gene expression.

Primary intraosseous fibrosarcoma in a cat.

PubMed

Fox, S M; Cooke, M M; Beban, H J

1995-10-01

A case of primary intraosseous fibrosarcoma of the left femur in a cat was diagnosed at necropsy following 9 months of managing a fracture of the same bone. Case features were those of probable pathological fracture, fracture repair and ultimate lysis of all but a fragment of the distal femoral epiphysis. Histology revealed closely packed whorls of fibroblasts typical of fibrosarcoma. This neoplasm is rare in the cat.

The MafA Transcription Factor Becomes Essential to Islet β-Cells Soon After Birth

PubMed Central

Hang, Yan; Yamamoto, Tsunehiko; Benninger, Richard K.P.; Brissova, Marcela; Guo, Min; Bush, Will; Piston, David W.; Powers, Alvin C.; Magnuson, Mark; Thurmond, Debbie C.; Stein, Roland

2014-01-01

The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial–temporal patterns in rodent islet cells. Analysis of Mafa−/− and pancreas-specific Mafa∆panc deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in MafaΔpanc mice and compromised earlier in MafaΔpanc;Mafb+/− mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB. PMID:24520122

Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis.

PubMed

Inui, Toshio; Katsuura, Goro; Kubo, Kentaro; Kuchiike, Daisuke; Chenery, Leslye; Uto, Yoshihiro; Nishikata, Takahito; Mette, Martin

2016-07-01

Gc protein-derived macrophage-activating factor (GcMAF) has various functions as an immune modulator, such as macrophage activation, anti-angiogenic activity and anti-tumor activity. Clinical trials of second-generation GcMAF demonstrated remarkable clinical effects in several types of cancers. Thus, GcMAF-based immunotherapy has a wide application for use in the treatment of many diseases via macrophage activation that can be used as a supportive therapy. Multiple sclerosis (MS) is considered to be an autoimmune disorder that affects the myelinated axons in the central nervous system (CNS). This study was undertaken to examine the effects of second-generation GcMAF in a patient with MS. This case study demonstrated that treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction. GcMAF shows therapeutic potency in the treatment of MS. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

PubMed

Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

2014-01-01

Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

MafA is required for postnatal proliferation of pancreatic β-cells.

PubMed

Eto, Koki; Nishimura, Wataru; Oishi, Hisashi; Udagawa, Haruhide; Kawaguchi, Miho; Hiramoto, Masaki; Fujiwara, Toshiyoshi; Takahashi, Satoru; Yasuda, Kazuki

2014-01-01

The postnatal proliferation and maturation of insulin-secreting pancreatic β-cells are critical for glucose metabolism and disease development in adults. Elucidation of the molecular mechanisms underlying these events will be beneficial to direct the differentiation of stem cells into functional β-cells. Maturation of β-cells is accompanied by increased expression of MafA, an insulin gene transcription factor. Transcriptome analysis of MafA knockout islets revealed MafA is required for the expression of several molecules critical for β-cell function, including Glut2, ZnT8, Granuphilin, Vdr, Pcsk1 and Urocortin 3, as well as Prolactin receptor (Prlr) and its downstream target Cyclin D2 (Ccnd2). Inhibition of MafA expression in mouse islets or β-cell lines resulted in reduced expression of Prlr and Ccnd2, and MafA transactivated the Prlr promoter. Stimulation of β-cells by prolactin resulted in the phosphorylation and translocation of Stat5B and an increased nuclear pool of Ccnd2 via Prlr and Jak2. Consistent with these results, the loss of MafA resulted in impaired proliferation of β-cells at 4 weeks of age. These results suggest that MafA regulates the postnatal proliferation of β-cells via prolactin signaling.

The LSST Metrics Analysis Framework (MAF)

NASA Astrophysics Data System (ADS)

Jones, R. Lynne; Yoachim, Peter; Chandrasekharan, Srinivasan; Connolly, Andrew J.; Cook, Kem H.; Ivezic, Zeljko; Krughoff, K. Simon; Petry, Catherine E.; Ridgway, Stephen T.

2015-01-01

Studying potential observing strategies or cadences for the Large Synoptic Survey Telescope (LSST) is a complicated but important problem. To address this, LSST has created an Operations Simulator (OpSim) to create simulated surveys, including realistic weather and sky conditions. Analyzing the results of these simulated surveys for the wide variety of science cases to be considered for LSST is, however, difficult. We have created a Metric Analysis Framework (MAF), an open-source python framework, to be a user-friendly, customizable and easily extensible tool to help analyze the outputs of the OpSim.MAF reads the pointing history of the LSST generated by the OpSim, then enables the subdivision of these pointings based on position on the sky (RA/Dec, etc.) or the characteristics of the observations (e.g. airmass or sky brightness) and a calculation of how well these observations meet a specified science objective (or metric). An example simple metric could be the mean single visit limiting magnitude for each position in the sky; a more complex metric might be the expected astrometric precision. The output of these metrics can be generated for a full survey, for specified time intervals, or for regions of the sky, and can be easily visualized using a web interface.An important goal for MAF is to facilitate analysis of the OpSim outputs for a wide variety of science cases. A user can often write a new metric to evaluate OpSim for new science goals in less than a day once they are familiar with the framework. Some of these new metrics are illustrated in the accompanying poster, "Analyzing Simulated LSST Survey Performance With MAF".While MAF has been developed primarily for application to OpSim outputs, it can be applied to any dataset. The most obvious examples are examining pointing histories of other survey projects or telescopes, such as CFHT.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF.

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-07-01

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.

Ameloblastic fibrosarcoma. Report of a case in a Nigerian.

PubMed

Adekeye, E O; Edwards, M B; Goubran, G F

1978-08-01

Ameloblastic fibrosarcoma is very rare and has not previously been reported from Nigeria. The case described here had typical clinical features, but the microscopic findings were unusual and difficult to interpret. The pathogenetic relationship between ameloblastic fibroma and fibrosarcoma is discussed.

Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

PubMed

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

2003-01-01

Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF1

PubMed Central

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki

2008-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years. PMID:18633461

Mitogen-activated protein kinase pathway mediates DBP-maf-induced apoptosis in RAW 264.7 macrophages.

PubMed

Gumireddy, Kiranmai; Reddy, C Damodar; Swamy, Narasimha

2003-09-01

Vitamin D-binding protein-macrophage-activating factor (DBP-maf) is derived from serum vitamin D binding protein (DBP) by selective deglycosylation during inflammation. In the present study, we investigated the effect of DBP-maf on RAW 264.7 macrophages and the underlying intracellular signal transduction pathways. DBP-maf increased proapoptotic caspase-3, -8, and -9 activities and induced apoptosis in RAW 264.7 cells. However, DBP, the precursor to DBP-maf did not induce apoptosis in these cells. Cell cycle analysis of DBP-maf-treated RAW 264.7 cells revealed growth arrest with accumulation of cells in sub-G(0)/G(1) phase. We also investigated the role of mitogen-activated protein kinase (MAPK) pathways in the DBP-maf-induced apoptosis of RAW264.7 cells. DBP-maf increased the phosphorylation of p38 and JNK1/2, while it decreased the ERK1/2 phosphorylation. Treatment with the p38 MAPK inhibitor, SB202190, attenuated DBP-maf-induced apoptosis. PD98059, a MEK specific inhibitor, did not show a significant inhibition of apoptosis induced by DBP-maf. Taken together, these results suggest that the p38 MAPK pathway plays a crucial role in DBP-maf-mediated apoptosis of macrophages. Our studies indicate that, during inflammation DBP-maf may function positively by causing death of the macrophages when activated macrophages are no longer needed at the site of inflammation. In summary, we report for the first time that DBP-maf induces apoptosis in macrophages via p38 and JNK1/2 pathway. Copyright 2003 Wiley-Liss, Inc.

Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.

PubMed

Xu, Jian; Du, Yue; Liu, Wen-Juan; Li, Liang; Li, Yi; Wang, Xiao-Fei; Yi, Hong-Fei; Shan, Chuan-Kun; Xia, Gui-Min; Liu, Xiu-Jun; Zhen, Yong-Su

2018-11-01

Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.

PubMed

Bonhoure, Nicolas; Byrnes, Ashlee; Moir, Robyn D; Hodroj, Wassim; Preitner, Frédéric; Praz, Viviane; Marcelin, Genevieve; Chua, Streamson C; Martinez-Lopez, Nuria; Singh, Rajat; Moullan, Norman; Auwerx, Johan; Willemin, Gilles; Shah, Hardik; Hartil, Kirsten; Vaitheesvaran, Bhavapriya; Kurland, Irwin; Hernandez, Nouria; Willis, Ian M

2015-05-01

MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences. © 2015 Bonhoure et al.; Published by Cold Spring Harbor Laboratory Press.

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance

PubMed Central

Bonhoure, Nicolas; Byrnes, Ashlee; Moir, Robyn D.; Hodroj, Wassim; Preitner, Frédéric; Praz, Viviane; Marcelin, Genevieve; Chua, Streamson C.; Martinez-Lopez, Nuria; Singh, Rajat; Moullan, Norman; Auwerx, Johan; Willemin, Gilles; Shah, Hardik; Hartil, Kirsten; Vaitheesvaran, Bhavapriya; Kurland, Irwin

2015-01-01

MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1−/− mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1−/− mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD+, and is associated with obesity resistance. Consistent with this, NAD+ levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences. PMID:25934505

Destructive Fibrosarcoma of the Maxillary Sinus.

PubMed

Ekinci, Adnan; Karataş, Duran; Yetiş, Abdurrahman; Erenler, Behice Hande; Ozcan, Muge

2018-05-01

Paranasal fibrosarcoma of nasal cavity and paranasal sinuses is a very rare malignant tumor. It is usually presented with nasal obstruction and epistaxis. In this clinical report, clinical symptoms, pathogenesis, and treatment principles of a paranasal fibrosarcoma originating from the right maxillary sinus and obstructing the right nasal passage are discussed.A 55-year-old male patient was admitted to the authors clinic with complaints of nasal obstruction and epistaxis lasting for 2 years. Anterior rhinoscopy revealed a mass lesion which obstructed the right nasal passage and caused frequent epistaxis. An opacity consistent with soft tissue lesion which was originated from the right maxillary sinus and filled the right nasal passage was observed in paranasal tomography. Magnetic resonance imaging revealed that the mass lesion was contrasted. Tumor was seen to erode orbital floor, and lateral and anterior walls of the maxillary sinus. Biopsy result was reported as papilloma. The patient was treated with Denker approach as anterior wall of the maxillary sinus was eroded by the tumor lesion and the mass lesion was excised. The patient received postoperative radiotherapy as pathological diagnosis was reported as paranasal fibrosarcoma.

Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis.

PubMed

Kanda, Shigeru; Mochizuki, Yasushi; Miyata, Yasuyoshi; Kanetake, Hiroshi; Yamamoto, Nobuto

2002-09-04

The vitamin D(3)-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) activates tumoricidal macrophages against a variety of cancers indiscriminately. We investigated whether GcMAF also acts as an antiangiogenic factor on endothelial cells. The effects of GcMAF on angiogenic growth factor-induced cell proliferation, chemotaxis, and tube formation were examined in vitro by using cultured endothelial cells (murine IBE cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs]) and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1, which is also a possible receptor for GcMAF, were used to investigate the mechanism of GcMAF action. GcMAF inhibited the endothelial cell proliferation, chemotaxis, and tube formation that were all stimulated by fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation of endothelial cell chemotaxis. In addition to its ability to activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on endothelial cells independent of tissue origin. The antiangiogenic effects of GcMAF may be mediated through the CD36 receptor.

Nasal cavity ossifying fibrosarcoma: an unusual fibro-osseous neoplasm.

PubMed

Alameda, Yadiel A; Perez-Mitchell, Carlos; Busquets, José M

2010-11-01

We describe the case of a 65-year-old woman who presented with left nasal obstruction. Clinical and radiographic examinations revealed the presence of a soft-tissue mass that had obliterated the left nasal cavity. The mass was completely excised via an endoscopic approach. Histopathologic examination identified the tumor as an ossifying fibrosarcoma. The patient recovered uneventfully and remained free of disease at the 2-year postoperative follow-up. To the best of our knowledge, no case of an ossifying fibrosarcoma of the nasal cavity has been previously reported in the English-language literature. We discuss the features of this case and the clinical presentation, diagnosis, and management of fibrosarcomas of the nasal cavity and paranasal sinuses.

Isolation and Functional Characterization of a Floral Repressor, BcMAF1, From Pak-choi (Brassica rapa ssp. Chinensis).

PubMed

Huang, Feiyi; Liu, Tongkun; Hou, Xilin

2018-01-01

MADS-box genes form a large gene family in plants and are involved in multiple biological processes, such as flowering. However, the regulation mechanism of MADS-box genes in flowering remains unresolved, especially under short-term cold conditions. In the present study, we isolated BcMAF1 , a Pak-choi ( Brassica rapa ssp. Chinensis ) MADS AFFECTING FLOWERING ( MAF ), as a floral repressor and functionally characterized BcMAF1 in Arabidopsis and Pak-choi. Subcellular localization and sequence analysis indicated that BcMAF1 was a nuclear protein and contained a conserved MADS-box domain. Expression analysis revealed that BcMAF1 had higher expression levels in leaves, stems, and petals, and could be induced by short-term cold conditions in Pak-choi. Overexpressing BcMAF1 in Arabidopsis showed that BcMAF1 had a negative function in regulating flowering, which was further confirmed by silencing endogenous BcMAF1 in Pak-choi. In addition, qPCR results showed that AtAP3 expression was reduced and AtMAF2 expression was induced in BcMAF1 -overexpressing Arabidopsis . Meanwhile, BcAP3 transcript was up-regulated and BcMAF2 transcript was down-regulated in BcMAF1 -silencing Pak-choi. Yeast one-hybrid and dual luciferase transient assays showed that BcMAF1 could bind to the promoters of BcAP3 and BcMAF2 . These results indicated that BcAP3 and BcMAF2 might be the targets of BcMAF1. Taken together, our results suggested that BcMAF1 could negatively regulate flowering by directly activating BcMAF2 and repressing BcAP3 .

A rare sinonasal neoplasm: fibrosarcoma.

PubMed

Bercin, Sami; Muderris, Togay; Kırıs, Muzaffer; Kanmaz, Alper; Kandemir, Olcay

2011-05-01

Sinonasal fibrosarcoma is an infrequently occurring malignant neoplasm. It usually presents with nasal obstruction and epistaxis, as do other sarcomas in this region. The final diagnosis is based on the histopathologic and immunohistochemical examination. We report a case involving a 47-year-old woman with a 2-year history of left nasal obstruction and proptosis, as well as diplopia for the 2 months preceding her visit. Computed tomography and magnetic resonance imaging showed a neoplasm occupying the left nasal cavity, ethmoid sinuses, and bilateral frontal sinuses. The neoplasm also was eroding the medial wall of the maxillary sinus, the lamina papyracea, the cribriform plate, and the anterior wall of the frontal sinus. Complete removal of the tumor was achieved both endoscopically and through a Lynch incision. Sinonasal fibrosarcoma was found on histopathologic examination.

Feline fibrosarcoma: perioperative management.

PubMed

Davis, Kechia M; Hardie, Elizabeth M; Lascelles, B Duncan X; Hansen, Bernie

2007-12-01

Aggressive and complete surgical excision is the treatment of choice for fibrosarcomas in cats. Thorough preoperative planning and meticulous surgical technique are necessary for optimal cosmetic, functional, and oncologic outcome. Perioperative pain management with an emphasis on preemptive analgesia and multimodal analgesia is essential to minimize patient morbidity.

Crystal Structure and Regulation of the Citrus Pol III Repressor MAF1 by Auxin and Phosphorylation.

PubMed

Soprano, Adriana Santos; Giuseppe, Priscila Oliveira de; Shimo, Hugo Massayoshi; Lima, Tatiani Brenelli; Batista, Fernanda Aparecida Heleno; Righetto, Germanna Lima; Pereira, José Geraldo de Carvalho; Granato, Daniela Campos; Nascimento, Andrey Fabricio Ziem; Gozzo, Fabio Cesar; de Oliveira, Paulo Sérgio Lopes; Figueira, Ana Carolina Migliorini; Smetana, Juliana Helena Costa; Paes Leme, Adriana Franco; Murakami, Mario Tyago; Benedetti, Celso Eduardo

2017-09-05

MAF1 is the main RNA polymerase (Pol) III repressor that controls cell growth in eukaryotes. The Citrus ortholog, CsMAF1, was shown to restrict cell growth in citrus canker disease but its role in plant development and disease is still unclear. We solved the crystal structure of the globular core of CsMAF1, which reveals additional structural elements compared with the previously available structure of hMAF1, and explored the dynamics of its flexible regions not present in the structure. CsMAF1 accumulated in the nucleolus upon leaf excision, and this translocation was inhibited by auxin and by mutation of the PKA phosphorylation site, S45, to aspartate. Additionally, mTOR phosphorylated recombinant CsMAF1 and the mTOR inhibitor AZD8055 blocked canker formation in normal but not CsMAF1-silenced plants. These results indicate that the role of TOR on cell growth induced by Xanthomonas citri depends on CsMAF1 and that auxin controls CsMAF1 interaction with Pol III in citrus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of fibrosarcoma in a maned wolf (Chrysocyon brachyurus) by rostral maxillectomy.

PubMed

McNulty, E E; Gilson, S D; Houser, B S; Ouse, A

2000-09-01

A 12-yr-old captive intact male maned wolf (Chrysocyon brachyurus) was diagnosed with a fibrosarcoma of the incisive bones. The mass was excised by rostral maxillectomy, and the wolf remained normal and on display with good function and cosmetics for 7 mo. Subsequently, it became weak, ataxic, and dyspneic and was euthanatized. At necropsy, there was a small regrowth of the maxillary tumor, a metastatic mediastinal mass, and multiple metastatic lung masses, suggesting that oral fibrosarcoma in maned wolves behaves similarly to oral fibrosarcoma in domestic canines. Aggressive surgical treatment of oral fibrosarcoma in this species can achieve good functional and cosmetic results.

Deregulated Methionine Adenosyltransferase α1, c-Myc and Maf Proteins Interplay Promotes Cholangiocarcinoma Growth in Mice and Humans

PubMed Central

Yang, Heping; Liu, Ting; Wang, Jiaohong; Li, Tony W.H.; Fan, Wei; Peng, Hui; Krishnan, Anuradha; Gores, Gregory J.; Mato, Jose M.; Lu, Shelly C.

2016-01-01

We reported c-Myc induction drives cholestatic liver injury and cholangiocarcinoma (CCA) in mice. We also showed induction of Maf proteins (MafG and c-Maf) contributed to cholestatic liver injury, whereas S-adenosylmethionine (SAMe) administration was protective. Here we determined whether there is interplay between c-Myc, Maf proteins and methionine adenosyltransferase α1 (MATα1), which is responsible for SAMe biosynthesis in liver. We used bile duct ligation (BDL) and lithocholic acid (LCA) treatment in mice as chronic cholestasis models, a murine CCA model, human CCA cell lines KMCH and Huh-28, human liver cancer HepG2, and human CCA specimens to study gene and protein expression, protein-protein interactions, molecular mechanisms and functional outcomes. We found c-Myc, MATα1 (encoded by MAT1A), MafG and c-Maf interact with each other directly. MAT1A expression fell in hepatocytes and bile duct epithelial cells during chronic cholestasis and in murine and human CCA. The opposite occurred with c-Myc, MafG and c-Maf expression. MATα1 interacts mainly with Mnt in normal liver but this switches to c-Maf, MafG and c-Myc in cholestatic livers and CCA. Promoter regions of these genes have E-boxes that are bound by MATα1 and Mnt in normal liver and benign bile duct epithelial cells that switched to c-Myc, c-Maf and MafG in cholestasis and CCA cells. E-box positively regulates c-Myc, MafG and c-Maf, but it negatively regulates MAT1A. MATα1 represses whereas c-Myc, MafG and c-Maf enhance E-box-driven promoter activity. Knocking down MAT1A or overexpressing MafG or c-Maf enhanced CCA growth and invasion in vivo. Conclusion We have uncovered a novel interplay between MATα1, c-Myc and Maf proteins and their deregulation during chronic cholestasis may facilitate CCA oncogenesis. PMID:26969892

Soft tissue fibrosarcoma of pre maxillary region in an adult: report of a unique pathological entity

PubMed Central

Naik, Smitha K.; Astekar, Madhusudhan; Rao, Dinesh

2012-01-01

Fibrosarcoma of the oral and maxillofacial region is a rare entity with poor prognosis. Most common sites are the extremities, with only one percent of fibrosarcoma arising in the head and neck area. Oral fibrosarcoma are locally infiltrative and destructive, spreads by haematogenous dissemination. The positive immunostaining for vimentin, together with negativity for muscular immunomarkers help to diagnosis the fibrosarcoma. Surgical management of fibrosarcoma in maxillofacial region is far from satisfactory, because of lack of inadequate clearance. This paper describes an unusual case of soft tissue fibrosarcoma of premaxillary region in an adult aged 71 years. PMID:24765457

Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

PubMed

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-01-01

Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

The transcription factor Lc-Maf participates in Col27a1 regulation during chondrocyte maturation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayo, Jaime L.; Holden, Devin N.; Barrow, Jeffery R.

2009-08-01

The transcription factor Lc-Maf, which is a splice variant of c-Maf, is expressed in cartilage undergoing endochondral ossification and participates in the regulation of type II collagen through a cartilage-specific Col2a1 enhancer element. Type XXVII and type XI collagens are also expressed in cartilage during endochondral ossification, and so enhancer/reporter assays were used to determine whether Lc-Maf could regulate cartilage-specific enhancers from the Col27a1 and Col11a2 genes. The Col27a1 enhancer was upregulated over 4-fold by Lc-Maf, while the Col11a2 enhancer was downregulated slightly. To confirm the results of these reporter assays, rat chondrosarcoma (RCS) cells were transiently transfected with anmore » Lc-Maf expression plasmid, and quantitative RT-PCR was performed to measure the expression of endogenous Col27a1 and Col11a2 genes. Endogenous Col27a1 was upregulated 6-fold by Lc-Maf overexpression, while endogenous Col11a2 was unchanged. Finally, in situ hybridization and immunohistochemistry were performed in the radius and ulna of embryonic day 17 mouse forelimbs undergoing endochondral ossification. Results demonstrated that Lc-Maf and Col27a1 mRNAs are coexpressed in proliferating and prehypertrophic regions, as would be predicted if Lc-Maf regulates Col27a1 expression. Type XXVII collagen protein was also most abundant in prehypertrophic and proliferating chondrocytes. Others have shown that mice that are null for Lc-Maf and c-Maf have expanded hypertrophic regions with reduced ossification and delayed vascularization. Separate studies have indicated that Col27a1 may serve as a scaffold for ossification and vascularization. The work presented here suggests that Lc-Maf may affect the process of endochondral ossification by participating in the regulation of Col27a1 expression.« less

mTORC1 directly phosphorylates and regulates human MAF1.

PubMed

Michels, Annemieke A; Robitaille, Aaron M; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H; Hall, Michael N; Hernandez, Nouria

2010-08-01

mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

PubMed

Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

2013-07-01

The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

Maf1 Protein, Repressor of RNA Polymerase III, Indirectly Affects tRNA Processing*

PubMed Central

Karkusiewicz, Iwona; Turowski, Tomasz W.; Graczyk, Damian; Towpik, Joanna; Dhungel, Nripesh; Hopper, Anita K.; Boguta, Magdalena

2011-01-01

Maf1 is negative regulator of RNA polymerase III in yeast. We observed high levels of both primary transcript and end-matured, intron-containing pre-tRNAs in the maf1Δ strain. This pre-tRNA accumulation could be overcome by transcription inhibition, arguing against a direct role of Maf1 in tRNA maturation and suggesting saturation of processing machinery by the increased amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one reason why end-matured intron-containing pre-tRNAs accumulate in maf1Δ cells. However, it is likely possible that other components of the processing pathway are also limiting when tRNA transcription is increased. According to our model, Maf1-mediated transcription control and nuclear export by Los1 are two major stages of tRNA biosynthesis that are regulated by environmental conditions in a coordinated manner. PMID:21940626

Maf1 protein, repressor of RNA polymerase III, indirectly affects tRNA processing.

PubMed

Karkusiewicz, Iwona; Turowski, Tomasz W; Graczyk, Damian; Towpik, Joanna; Dhungel, Nripesh; Hopper, Anita K; Boguta, Magdalena

2011-11-11

Maf1 is negative regulator of RNA polymerase III in yeast. We observed high levels of both primary transcript and end-matured, intron-containing pre-tRNAs in the maf1Δ strain. This pre-tRNA accumulation could be overcome by transcription inhibition, arguing against a direct role of Maf1 in tRNA maturation and suggesting saturation of processing machinery by the increased amounts of primary transcripts. Saturation of the tRNA exportin, Los1, is one reason why end-matured intron-containing pre-tRNAs accumulate in maf1Δ cells. However, it is likely possible that other components of the processing pathway are also limiting when tRNA transcription is increased. According to our model, Maf1-mediated transcription control and nuclear export by Los1 are two major stages of tRNA biosynthesis that are regulated by environmental conditions in a coordinated manner.

Fibrosarcoma of the urinary bladder in a cat.

PubMed

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela; Greci, Valentina

2015-01-01

A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia.

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF.

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Nakazato, Hiroaki; Yamamoto, Nobuyuki; Koga, Yoshihiko

2008-07-01

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.

Infantile fibrosarcoma of the penis in a 2-year-old boy.

PubMed

Taib, Fahisham; Mohamad, Norsarwany; Mohamed Daud, Mohamed Ashraf; Hassan, Aniza; Singh, Mutum Samarendra; Nasir, Ariffin

2012-10-01

Fibrosarcoma is rare in the pediatric age group. It generally involves the extremities and the trunk but rarely involves the genital area. We report a case of a large fungating infantile fibrosarcoma of the penis in a 2-year-old Malay boy. Partial recovery of the penile structure was achieved after chemotherapy. The difficulty in managing the social and surgical aspect of this case is discussed in our report. To the best of our knowledge, this is the first case report of infantile fibrosarcoma involving the penis in an Asian region. Copyright © 2012 Elsevier Inc. All rights reserved.

Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors.

PubMed

Motohashi, Hozumi; O'Connor, Tania; Katsuoka, Fumiki; Engel, James Douglas; Yamamoto, Masayuki

2002-07-10

Recent progress in the analysis of transcriptional regulation has revealed the presence of an exquisite functional network comprising the Maf and Cap 'n' collar (CNC) families of regulatory proteins, many of which have been isolated. Among Maf factors, large Maf proteins are important in the regulation of embryonic development and cell differentiation, whereas small Maf proteins serve as obligatory heterodimeric partner molecules for members of the CNC family. Both Maf homodimers and CNC-small Maf heterodimers bind to the Maf recognition element (MARE). Since the MARE contains a consensus TRE sequence recognized by AP-1, Jun and Fos family members may act to compete or interfere with the function of CNC-small Maf heterodimers. Overall then, the quantitative balance of transcription factors interacting with the MARE determines its transcriptional activity. Many putative MARE-dependent target genes such as those induced by antioxidants and oxidative stress are under concerted regulation by the CNC family member Nrf2, as clearly proven by mouse germline mutagenesis. Since these genes represent a vital aspect of the cellular defense mechanism against oxidative stress, Nrf2-null mutant mice are highly sensitive to xenobiotic and oxidative insults. Deciphering the molecular basis of the regulatory network composed of Maf and CNC families of transcription factors will undoubtedly lead to a new paradigm for the cooperative function of transcription factors.

Improving esthetic results in benign parotid surgery: statistical evaluation of facelift approach, sternocleidomastoid flap, and superficial musculoaponeurotic system flap application.

PubMed

Bianchi, Bernardo; Ferri, Andrea; Ferrari, Silvano; Copelli, Chiara; Sesenna, Enrico

2011-04-01

The purpose of this article was to analyze the efficacy of facelift incision, sternocleidomastoid muscle flap, and superficial musculoaponeurotic system flap for improving the esthetic results in patients undergoing partial parotidectomy for benign parotid tumor resection. The usefulness of partial parotidectomy is discussed, and a statistical evaluation of the esthetic results was performed. From January 1, 1996, to January 1, 2007, 274 patients treated for benign parotid tumors were studied. Of these, 172 underwent partial parotidectomy. The 172 patients were divided into 4 groups: partial parotidectomy with classic or modified Blair incision without reconstruction (group 1), partial parotidectomy with facelift incision and without reconstruction (group 2), partial parotidectomy with facelift incision associated with sternocleidomastoid muscle flap (group 3), and partial parotidectomy with facelift incision associated with superficial musculoaponeurotic system flap (group 4). Patients were considered, after a follow-up of at least 18 months, for functional and esthetic evaluation. The functional outcome was assessed considering the facial nerve function, Frey syndrome, and recurrence. The esthetic evaluation was performed by inviting the patients and a blind panel of 1 surgeon and 2 secretaries of the department to give a score of 1 to 10 to assess the final cosmetic outcome. The statistical analysis was finally performed using the Mann-Whitney U test for nonparametric data to compare the different group results. P less than .05 was considered significant. No recurrence developed in any of the 4 groups or in any of the 274 patients during the follow-up period. The statistical analysis, comparing group 1 and the other groups, revealed a highly significant statistical difference (P < .0001) for all groups. Also, when group 2 was compared with groups 3 and 4, the difference was highly significantly different statistically (P = .0018 for group 3 and P = .0005 for

Inhibition of angiogenesis by vitamin D-binding protein: characterization of anti-endothelial activity of DBP-maf.

PubMed

Kalkunte, Satyan; Brard, Laurent; Granai, Cornelius O; Swamy, Narasimha

2005-01-01

Angiogenesis is a complex process involving coordinated steps of endothelial cell activation, proliferation, migration, tube formation and capillary sprouting with participation of intracellular signaling pathways. Regulation of angiogenesis carries tremendous potential for cancer therapy. Our earlier studies showed that vitamin D-binding protein-macrophage activating factor (DBP-maf) acts as a potent anti-angiogenic factor and inhibits tumor growth in vivo. The goal of this investigation was to understand the effect of DBP-maf on human endothelial cell (HEC) and the mechanism of angiogenesis inhibition. DBP-maf inhibited human endothelial cell (HEC) proliferation by inhibiting DNA synthesis (IC(50) = 7.8 +/- 0.15 microg/ml). DBP-maf significantly induced S- and G0/G1-phase arrest in HEC in 72 h. DBP-maf potently blocked VEGF-induced migration, tube-formation of HEC in a dose dependent manner. In addition, DBP-maf inhibited growth factor-induced microvessel sprouting in rat aortic ring assay. Moreover, DBP-maf inhibited VEGF signaling by decreasing VEGF-mediated phosphorylation of VEGFR-2 and ERK1/2, a downstream target of VEGF signaling cascade. However, Akt activation was not affected. These studies collectively demonstrate that DBP-maf inhibits angiogenesis by blocking critical steps such as HEC proliferation, migration, tube formation and microvessel sprouting. DBP-maf exerts its effect by inhibiting VEGR-2 and ERK1/2 signaling cascades. Understanding the cellular and molecular mechanisms of anti-endothelial activity of DBP-maf will allow us to develop it as an angiogenesis targeting novel drug for tumor therapy.

Protection and governance of MPEG-21 music player MAF contents using MPEG-21 IPMP tools

NASA Astrophysics Data System (ADS)

Hendry; Kim, Munchurl

2006-02-01

MPEG (Moving Picture Experts Groups) is currently standardizing Multimedia Application Format (MAF) which targets to provide simple but practical multimedia applications to the industry. One of the interesting and on-going working items of MAF activity is the so-called Music Player MAF which combines MPEG-1/2 layer III (MP3), JPEG image, and metadata into a standard format. In this paper, we propose a protection and governance mechanism to the Music Player MAF by incorporating other MPEG technology, MPEG-21 IPMP (Intellectual Property Management and Protection). We show, in this paper, use-case of the distribution and consumption of this Music Player contents, requirements, and how this protection and governance can be implemented in conjunction with the current Music Player MAF architecture and file system. With the use of MPEG-21 IPMP, the protection and governance to the content of Music Player MAF fulfils flexibility, extensibility, and granular in protection requirements.

MafB antagonizes phenotypic alteration induced by GM-CSF in microglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koshida, Ryusuke, E-mail: rkoshida-myz@umin.ac.jp; Oishi, Hisashi, E-mail: hoishi@md.tsukuba.ac.jp; Hamada, Michito

2015-07-17

Microglia are tissue-resident macrophages which are distributed throughout the central nervous system (CNS). Recent studies suggest that microglia are a unique myeloid population distinct from peripheral macrophages in terms of origin and gene expression signature. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic cytokine regulating myeloid development, has been shown to stimulate proliferation and alter phenotype of microglia in vitro. However, how its signaling is modulated in microglia is poorly characterized. MafB, a bZip transcriptional factor, is highly expressed in monocyte-macrophage lineage cells including microglia, although its role in microglia is largely unknown. We investigated the crosstalk between GM-CSF signaling and MafB bymore » analyzing primary microglia. We found that Mafb-deficient microglia grew more rapidly than wild-type microglia in response to GM-CSF. Moreover, the expression of genes associated with microglial differentiation was more downregulated in Mafb-deficient microglia cultured with GM-CSF. Notably, such differences between the genotypes were not observed in the presence of M-CSF. In addition, we found that Mafb-deficient microglia cultured with GM-CSF barely extended their membrane protrusions, probably due to abnormal activation of RhoA, a key regulator of cytoskeletal remodeling. Altogether, our study reveals that MafB is a negative regulator of GM-CSF signaling in microglia. These findings could provide new insight into the modulation of cytokine signaling by transcription factors in microglia. - Highlights: • GM-CSF alters the phenotype of microglia in vitro more potently than M-CSF. • Transcription factor MafB antagonizes the effect of GM-CSF on microglia in vitro. • MafB deficiency leads to RhoA activation in microglia in response to GM-CSF. • We show for the first time the function of MafB in microglia.« less

mTORC1 Directly Phosphorylates and Regulates Human MAF1▿

PubMed Central

Michels, Annemieke A.; Robitaille, Aaron M.; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H.; Hall, Michael N.; Hernandez, Nouria

2010-01-01

mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. PMID:20516213

Fibrosarcoma of the urinary bladder in a cat

PubMed Central

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela

2015-01-01

Case summary A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months’ duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. Relevance and novel information To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia. PMID:28491352

Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF).

PubMed

Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki; Ushijima, Naofumi

2008-01-15

Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc protein with immobilized beta-galactosidase and sialidase generated probably the most potent macrophage activating factor (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with GcMAF (100 pg/ml) are highly tumoricidal to mammary adenocarcinomas. Efficacy of GcMAF for treatment of metastatic breast cancer was investigated with 16 nonanemic patients who received weekly administration of GcMAF (100 ng). As GcMAF therapy progresses, the MAF precursor activity of patient Gc protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to tumor burden, the time course progress of GcMAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg protein. After about 16-22 administrations (approximately 3.5-5 months) of GcMAF, these patients had insignificantly low serum enzyme levels equivalent to healthy control enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg protein, indicating eradication of the tumors. This therapeutic procedure resulted in no recurrence for more than 4 years. Copyright 2007 Wiley-Liss, Inc.

Facilitated recycling protects human RNA polymerase III from repression by Maf1 in vitro.

PubMed

Cabart, Pavel; Lee, JaeHoon; Willis, Ian M

2008-12-26

Yeast cells synthesize approximately 3-6 million molecules of tRNA every cell cycle at a rate of approximately 2-4 transcripts/gene/s. This high rate of transcription is achieved through many rounds of reinitiation by RNA polymerase (pol) III on stable DNA-bound complexes of the initiation factor TFIIIB. Studies in yeast have shown that the rate of reinitiation is increased by facilitated recycling, a process that involves the repeated reloading of the polymerase on the same transcription unit. However, when nutrients become limiting or stress conditions are encountered, RNA pol III transcription is rapidly repressed through the action of the conserved Maf1 protein. Here we examine the relationship between Maf1-mediated repression and facilitated recycling in a human RNA pol III in vitro system. Using an immobilized template transcription assay, we demonstrate that facilitated recycling is conserved from yeast to humans. We assessed the ability of recombinant human Maf1 to inhibit different steps in transcription before and after preinitiation complex assembly. We show that recombinant Maf1 can inhibit the recruitment of TFIIIB and RNA pol III to immobilized templates. However, RNA pol III bound to preinitiation complexes or in elongation complexes is protected from repression by Maf1 and can undergo several rounds of initiation. This indicates that recombinant Maf1 is unable to inhibit facilitated recycling. The data suggest that additional biochemical steps may be necessary for rapid Maf1-dependent repression of RNA pol III transcription.

Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

PubMed

Murua Escobar, Hugo; Günther, Kathrin; Richter, Andreas; Soller, Jan T; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

2004-01-01

Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes.

PubMed

Wen, Xianjie; Yang, Yisheng

2017-02-01

GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations. GLIS3 cooperates with pancreatic and duodenal homeobox 1 (PDX1), v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA), as well as neurogenic differentiation 1 (NEUROD1) and potently controls insulin gene transcription. GLIS3 also plays a role in β cell survival and likely in insulin secretion. Any perturbation of these functions may underlie all three forms of diabetes. GLIS3, synergistically with hepatocyte nuclear factor 6 (HNF6) and forkhead box A2 (FOXA2), controls fetal islet differentiation via transactivating neurogenin 3 (NGN3) and impairment of this function leads to neonatal diabetes. In addition, GLIS3 is also required for the compensatory β cell proliferation and mass expansion in response to insulin resistance, which if disrupted may predispose to T2D. The increasing understanding of the mechanisms of GLIS3 in β cell development, survival and function maintenance will provide new insights into disease pathogenesis and potential therapeutic target identification to combat diabetes. © 2017 Society for Endocrinology.

Altered MENIN expression disrupts the MAFA differentiation pathway in insulinoma.

PubMed

Hamze, Z; Vercherat, C; Bernigaud-Lacheretz, A; Bazzi, W; Bonnavion, R; Lu, J; Calender, A; Pouponnot, C; Bertolino, P; Roche, C; Stein, R; Scoazec, J Y; Zhang, C X; Cordier-Bussat, M

2013-12-01

The protein MENIN is the product of the multiple endocrine neoplasia type I (MEN1) gene. Altered MENIN expression is one of the few events that are clearly associated with foregut neuroendocrine tumours (NETs), classical oncogenes or tumour suppressors being not involved. One of the current challenges is to understand how alteration of MENIN expression contributes to the development of these tumours. We hypothesised that MENIN might regulate factors maintaining endocrine-differentiated functions. We chose the insulinoma model, a paradigmatic example of well-differentiated pancreatic NETs, to study whether MENIN interferes with the expression of v-MAF musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA), a master glucose-dependent transcription factor in differentiated β-cells. Immunohistochemical analysis of a series of human insulinomas revealed a correlated decrease in both MENIN and MAFA. Decreased MAFA expression resulting from targeted Men1 ablation was also consistently observed in mouse insulinomas. In vitro analyses using insulinoma cell lines showed that MENIN regulated MAFA protein and mRNA levels, and bound to Mafa promoter sequences. MENIN knockdown concomitantly decreased mRNA expression of both Mafa and β-cell differentiation markers (Ins1/2, Gck, Slc2a2 and Pdx1) and, in parallel, increased the proliferation rate of tumours as measured by bromodeoxyuridine incorporation. Interestingly, MAFA knockdown alone also increased proliferation rate but did not affect the expression of candidate proliferation genes regulated by MENIN. Finally, MENIN variants with missense mutations detected in patients with MEN1 lost the WT MENIN properties to regulate MAFA. Together, our findings unveil a previously unsuspected MENIN/MAFA connection regarding control of the β-cell differentiation/proliferation balance, which could contribute to tumorigenesis.

Current diagnostics and treatment of fibrosarcoma –perspectives for future therapeutic targets and strategies

PubMed Central

Augsburger, Daniela; Nelson, Peter J.; Kalinski, Thomas; Udelnow, Andrej; Knösel, Thomas; Hofstetter, Monika; Qin, Ji Wei; Wang, Yan; Gupta, Arvid Sen; Bonifatius, Susanne; Li, Minglun; Bruns, Christiane J.; Zhao, Yue

2017-01-01

Adult-type fibrosarcoma is a rare and highly aggressive subtype of soft tissue sarcomas. Due to the existence of other spindle-cell shaped sarcomas, its diagnosis is always one of exclusion. The likelihood of misdiagnoses between similar tumour entities is high, and often leads to inappropriate tumour treatment. We summarize here the main features of fibrosarcoma. When fibrosarcoma is appropriately diagnosed, the patient`s overall prognosis is generally quite poor. Fibrosarcoma is characterized by its low sensitivity towards radio- and chemotherapy as well as by its high rate of tumour recurrences. Thus it is important to identify new methods to improve treatment of this tumour entity. We discuss some promising new directions in fibrosarcoma research, specifically focusing on more effective targeting of the tumour microenvironment. Communication between tumour cells and their surrounding stromal tissue play a crucial role in cancer progression, invasion, metastasis and chemosensitivity. The therapeutic potential of targeting the tumour microenvironment is addressed. PMID:29262667

Sinonasal fibrosarcoma: analysis of the Surveillance, Epidemiology, and End Results database.

PubMed

Patel, Tapan D; Carniol, Eric T; Vázquez, Alejandro; Baredes, Soly; Liu, James K; Eloy, Jean Anderson

2016-02-01

Primary fibrosarcoma of the sinonasal region is an infrequently occurring malignant neoplasm. Fibrosarcomas are most commonly found in the extremities, with only 1% of fibrosarcomas reported in the head and neck region. This study analyzes the demographic, clinicopathologic, and survival characteristics of sinonasal fibrosarcoma (SNFS). The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2012) was queried for SNFS cases. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier model. Fifty-one cases of fibrosarcoma were identified in the sinonasal region. The mean age at diagnosis was 54.5 years and the mean survival was 119.7 months. There was no gender predilection with a male-to-female ratio of 1.04:1. The maxillary sinus was the most common site of involvement (54.9%), followed by the nasal cavity (23.5%). Five-year survival analysis revealed an overall survival rate of 71.7%, disease-specific survival rate of 77.8%, and relative survival (RS) rate of 78.8%. Disease-specific survival was better among those treated with surgery (with [76.2%] or without [87.5%] adjuvant radiotherapy) than those treated with primary radiotherapy alone (33.3%) (p = 0.0069). SNFS is a rare entity. This study represents the largest series of SNFS to date. The mainstay of treatment for this tumor is surgical resection with or without radiotherapy. © 2015 ARS-AAOA, LLC.

The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF.

PubMed

Odgren, P R; Popoff, S N; Safadi, F F; MacKay, C A; Mason-Savas, A; Seifert, M F; Marks, S C

1999-08-01

The osteopetrotic rat mutation toothless (tl) is characterized by little or no bone resorption, few osteoclasts and macrophages, and chondrodysplasia at the growth plates. Short-term treatment of tl rats with colony-stimulating factor-1 (CSF-1) has been shown to increase the number of osteoclasts and macrophages, producing dramatic resolution of skeletal sclerosis at some, but not all, sites. Defects in production of vitamin D-binding protein-macrophage activating factor (DBP-MAF) have been identified in two other independent osteopetrotic mutations of the rat (op and ia), and two in the mouse (op and mi), in which macrophages and osteoclasts can be activated by the administration of exogenous DBP-MAF. The present studies were undertaken to examine the histology and residual growth defects in tl rats following longer CSF-1 treatments, to investigate the possibility that exogenous DBP-MAF might act synergistically with CSF-1 to improve the tl phenotype, and to assess the integrity of the endogenous DBP-MAF pathway in this mutation. CSF-1 treatment-with or without DBP-MAF-induced resorption of metaphyseal bone to the growth plate on the marrow side, improved slightly but did not normalize long bone growth, and caused no improvement in the abnormal histology of the growth plate. Injections of lysophosphatidylcholine (lyso-Pc) to prime macrophage activation via the DBP-MAF pathway raised superoxide production to similar levels in peritoneal macrophages from both normal and mutant animals, indicating no defect in the DBP-MAF pathway in tl rats. Interestingly, pretreatments with CSF-1 alone also increased superoxide production, although the mechanism for this remains unknown. In summary, we find that, unlike other osteopetrotic mutations investigated to date, the DBP-MAF pathway does not appear to be defective in the tl rat; that additional DBP-MAF does not augment the beneficial skeletal effects seen with CSF-1 alone; and that the growth plate chondrodystrophy seen in

Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice.

PubMed

Kisker, Oliver; Onizuka, Shinya; Becker, Christian M; Fannon, Michael; Flynn, Evelyn; D'Amato, Robert; Zetter, Bruce; Folkman, Judah; Ray, Rahul; Swamy, Narasimha; Pirie-Shepherd, Steven

2003-01-01

We have isolated a selectively deglycosylated form of vitamin D binding protein (DBP-maf) generated from systemically available DBP by a human pancreatic cancer cell line. DBP-maf is antiproliferative for endothelial cells and antiangiogenic in the chorioallantoic membrane assay. DBP-maf administered daily was able to potently inhibit the growth of human pancreatic cancer in immune compromised mice (T/C=0.09). At higher doses, DBP-maf caused tumor regression. Histological examination revealed that treated tumors had a higher number of infiltrating macrophages as well as reduced microvessel density, and increased levels of apoptosis relative to untreated tumors. Taken together, these data suggest that DBP-maf is an antiangiogenic molecule that can act directly on endothelium as well as stimulate macrophages to attack both the endothelial and tumor cell compartment of a growing malignancy.

Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis.

PubMed

Suda, Natsuno; Itoh, Takehiko; Nakato, Ryuichiro; Shirakawa, Daisuke; Bando, Masashige; Katou, Yuki; Kataoka, Kohsuke; Shirahige, Katsuhiko; Tickle, Cheryll; Tanaka, Mikiko

2014-07-01

Apoptosis is an important mechanism for sculpting morphology. However, the molecular cascades that control apoptosis in developing limb buds remain largely unclear. Here, we show that MafB was specifically expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosis, whereas MafB/cJun heterodimers promoted apoptosis for sculpting the shape of the limbs. Chromatin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulatory elements controlled by Maf and Jun. Functional analyses revealed that expression of p63 and p73, key components known to arrest the cell cycle, was directly activated by MafB and cJun. Our data suggest that dimeric combinations of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and that MafB/cJun heterodimers lead to apoptosis via activation of p63 and p73. © 2014. Published by The Company of Biologists Ltd.

Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog.

PubMed

Brewer, W G; Turrel, J M

1982-07-15

Ten dogs with oral or external nasal fibrosarcoma were treated sequentially with orthovoltage radiation and radiofrequency (RF)-induced hyperthermia. Total radiation doses ranged from 3,200 to 4,800 rad given in 8 to 12 fractions of 400 rad. Immediately after 2 to 4 radiation treatments, hyperthermia was given. Six oral fibrosarcomas were heated to 50 C for 30 sec, using a hand-held RF generator. Four nasomaxillary fibrosarcomas were heated to 43 C for 30 minutes, using a 500-kHz RF generator. Hyperthermia of 50 C resulted in tumor necrosis and infection in 3 dogs and fatal septicemia in 1 dog. Nine of 10 tumors responded to therapy. One year after therapy, 5 dogs were free of disease. Tumor regrowth occurred in 5 dogs. Mean time to tumor regrowth and mean survival time of all dogs were 343 and 398 days, respectively. The results suggested that sequential radiation-hyperthermia is an effective therapeutic regimen for canine fibrosarcoma. It was concluded that this modality not only may be beneficial in the treatment of canine tumors but may be useful for designing new therapeutic approaches to similar tumors in man.

A designed glycoprotein analogue of Gc-MAF exhibits native-like phagocytic activity.

PubMed

Bogani, Federica; McConnell, Elizabeth; Joshi, Lokesh; Chang, Yung; Ghirlanda, Giovanna

2006-06-07

Rational protein design has been successfully used to create mimics of natural proteins that retain native activity. In the present work, de novo protein engineering is explored to develop a mini-protein analogue of Gc-MAF, a glycoprotein involved in the immune system activation that has shown anticancer activity in mice. Gc-MAF is derived in vivo from vitamin D binding protein (VDBP) via enzymatic processing of its glycosaccharide to leave a single GalNAc residue located on an exposed loop. We used molecular modeling tools in conjunction with structural analysis to splice the glycosylated loop onto a stable three-helix bundle (alpha3W, PDB entry 1LQ7). The resulting 69-residue model peptide, MM1, has been successfully synthesized by solid-phase synthesis both in the aglycosylated and the glycosylated (GalNAc-MM1) form. Circular dichroism spectroscopy confirmed the expected alpha-helical secondary structure. The thermodynamic stability as evaluated from chemical and thermal denaturation is comparable with that of the scaffold protein, alpha3W, indicating that the insertion of the exogenous loop of Gc-MAF did not significantly perturb the overall structure. GalNAc-MM1 retains the macrophage stimulation activity of natural Gc-MAF; in vitro tests show an identical enhancement of Fc-receptor-mediated phagocytosis in primary macrophages. GalNAc-MM1 provides a framework for the development of mutants with increased activity that could be used in place of Gc-MAF as an immunomodulatory agent in therapy.

Vaccine-associated fibrosarcoma in a cat.

PubMed

Martin, Melanie

2003-08-01

An 8-year-old, spayed, female domestic shorthair was diagnosed with a vaccine-associated fibrosarcoma and treated with full course radiation therapy, aggressive surgery, and postoperative chemotherapy. Histopathologic examination confirmed that excision of the tumor was complete. The cat was doing well 278 days after initial presentation.

Vaccine-associated fibrosarcoma in a cat

PubMed Central

Martin, Melanie

2003-01-01

An 8-year-old, spayed, female domestic shorthair was diagnosed with a vaccine- associated fibrosarcoma and treated with full course radiation therapy, aggressive surgery, and postoperative chemotherapy. Histopathologic examination confirmed that excision of the tumor was complete. The cat was doing well 278 days after initial presentation. PMID:13677599

Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity.

PubMed

Nagasawa, Hideko; Uto, Yoshihiro; Sasaki, Hideyuki; Okamura, Natsuko; Murakami, Aya; Kubo, Shinichi; Kirk, Kenneth L; Hori, Hitoshi

2005-01-01

The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research.

Bilateral uveal metastasis of a subcutaneous fibrosarcoma in a cat.

PubMed

Mowat, Freya M; Langohr, Ingeborg M; Bilyk, Olenka; Koterbay, Amy; Pierce, Kenneth E; Petersen-Jones, Simon M

2012-11-01

A 6-year-old neutered male domestic short-haired cat was presented to the Comparative Ophthalmology service at Michigan State University with a 3-week history of decreased appetite and redness of the left eye. The left forelimb had been removed 15 months previously because of the presence of a subcutaneous fibrosarcoma. In the left globe, a large iridal mass was associated with increased intraocular pressure and retinal detachment. A smaller mass involving the right iris was also present. Imaging revealed a 2-cm mass in the left caudodorsal lung lobe, and abdominal ultrasound showed multifocal bilateral renal masses. Aspirates of these masses were nondiagnostic. The left globe was removed for palliative reasons, and histopathology showed that fibrosarcoma was infiltrating the iris, choroid, and optic nerve. Despite systemic chemotherapy with doxorubicin, the animal died 4 months after initial presentation. Histopathology confirmed highly angioinvasive metastatic fibrosarcoma also in the right uveal tract, the lungs, and both kidneys. © 2012 American College of Veterinary Ophthalmologists.

Feline vaccine-associated fibrosarcoma: morphologic distinctions.

PubMed

Couto, S S; Griffey, S M; Duarte, P C; Madewell, B R

2002-01-01

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for alpha-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

β-Galactosidase treatment is a common first-stage modification of the three major subtypes of Gc protein to GcMAF.

PubMed

Uto, Yoshihiro; Yamamoto, Syota; Mukai, Hirotaka; Ishiyama, Noriko; Takeuchi, Ryota; Nakagawa, Yoshinori; Hirota, Keiji; Terada, Hiroshi; Onizuka, Shinya; Hori, Hitoshi

2012-06-01

The 1f1f subtype of the group-specific component (Gc) protein is converted into Gc protein-derived macrophage-activating factor (GcMAF) by enzymatic processing with β-galactosidase and sialidase. We previously demonstrated that preGc(1f1f)MAF, a full Gc(1f1f) protein otherwise lacking a galactosyl moiety, can be converted to GcMAF by treatment with mouse peritoneal fluid. Here, we investigated the effects of the β-galactosidase-treated 1s1s and 22 subtypes of Gc protein (preGc(1s1s)MAF and preGc₂₂MAF) on the phagocytic activation of mouse peritoneal macrophages. We demonstrated the presence of Gal-GalNAc disaccharide sugar structures in the Gc(1s1s) protein by western blotting using peanut agglutinin and Helix pomatia agglutinin lectin. We also found that preGc(1s1s)MAF and preGc₂₂MAF significantly enhanced the phagocytic activity of mouse peritoneal macrophages in the presence and absence of mouse peritoneal fluid. We demonstrate that preGc(1s1s)MAF and preGc₂₂MAF proteins can be used as effective macrophage activators.

Cell lines derived from feline fibrosarcoma display unstable chromosomal aneuploidy and additionally centrosome number aberrations.

PubMed

von Erichsen, J; Hecht, W; Löhberg-Gruene, C; Reinacher, M

2012-07-01

The purpose of the study was to evaluate clonality and presence of numerical chromosomal and centrosomal aberrations in 5 established feline fibrosarcoma cell lines and in a fetal dermal fibroblast cell line as a control. The clonality of all cell lines was examined using limited-dilution cloning. The number of chromosomes was counted in metaphase spreads. The immunocytochemical analysis of centrosome numbers was performed by indirect immunofluorescence using a monoclonal antibody that targets γ-tubulin, a well-characterized component of centrosomes. Monoclonal cell populations could be established from all cell lines. In all feline fibrosarcoma cell lines, the number of chromosomes deviated abnormally from the normal feline chromosome number of 2n = 38, ranging from 19 to 155 chromosomes per cell. Centrosome hyperamplification was observed in all 5 feline fibrosarcoma cell lines with a proportion of cells (5.7 to 15.2%) having more than 2 centrosomes. In the control cell line, only 0.6% of the cells had more than 2 centrosomes. In conclusion, the examinations revealed that centrosome hyperamplification occurs in feline fibrosarcoma cell lines. The feline fibrosarcoma cell lines possessed 10 to 25 times as many cells with centrosome hyperamplification as the control cell line. These observations suggest an association of numerical centrosome aberrations with karyotype instability by increasing the frequency of chromosome missegregation. The results of this study may be helpful for further characterization of feline fibrosarcomas and may contribute to the knowledge of cytogenetic factors that may be important for the pathogenesis of feline fibrosarcomas.

Effect of the Gc-derived macrophage-activating factor precursor (preGcMAF) on phagocytic activation of mouse peritoneal macrophages.

PubMed

Uto, Yoshihiro; Yamamoto, Syota; Takeuchi, Ryota; Nakagawa, Yoshinori; Hirota, Keiji; Terada, Hiroshi; Onizuka, Shinya; Nakata, Eiji; Hori, Hitoshi

2011-07-01

The 1f1f subtype of the Gc protein (Gc(1f1f) protein) was converted into Gc-derived macrophage-activating factor (GcMAF) by enzymatic processing in the presence of β-galactosidase of an activated B-cell and sialidase of a T-cell. We hypothesized that preGc(1f1f)MAF, the only Gc(1f1f) protein lacking galactose, can be converted to GcMAF in vivo because sialic acid is cleaved by residual sialidase. Hence, we investigated the effect of preGc(1f1f)MAF on the phagocytic activation of mouse peritoneal macrophages. We examined the sugar moiety of preGc(1f1f)MAF with a Western blot using peanut agglutinin (PNA) and Helix pomatia agglutinin (HPA) lectin. We also found that preGc(1f1f)MAF significantly enhanced phagocytic activity in mouse peritoneal macrophages but only in the presence of the mouse peritoneal fluid; the level of phagocytic activity was the same as that observed for GcMAF. PreGc(1f1f)MAF can be used as an effective macrophage activator in vivo.

Ameloblastic fibrosarcoma: Report of a case

PubMed Central

Akinyamoju, Akindayo O; Olusanya, Adeola A; Adeyemi, Bukola F; Kolude, B

2013-01-01

Ameloblastic fibrosarcoma (AFS) is a rare odontogenic malignancy with benign epithelial and malignant ectomesenchymal components. About 66 cases have been reported in the medical literature. We therefore report an additional case as well as a review of literature to add to the existing knowledge on this rare lesion. PMID:24574665

Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes.

PubMed

Wheaton, Joshua D; Yeh, Chen-Hao; Ciofani, Maria

2017-12-15

Regulatory T cells (Tregs) adopt specialized phenotypes defined by coexpression of lineage-defining transcription factors, such as RORγt, Bcl-6, or PPARγ, alongside Foxp3. These Treg subsets have unique tissue distributions and diverse roles in maintaining organismal homeostasis. However, despite extensive functional characterization, the factors driving Treg specialization are largely unknown. In this article, we show that c-Maf is a critical transcription factor regulating this process in mice, essential for generation of both RORγt + Tregs and T follicular regulatory cells, but not for adipose-resident Tregs. c-Maf appears to function primarily in Treg specialization, because IL-10 production, expression of other effector molecules, and general immune homeostasis are not c-Maf dependent. As in other T cells, c-Maf is induced in Tregs by IL-6 and TGF-β, suggesting that a combination of inflammatory and tolerogenic signals promote c-Maf expression. Therefore, c-Maf is a novel regulator of Treg specialization, which may integrate disparate signals to facilitate environmental adaptation. Copyright © 2017 by The American Association of Immunologists, Inc.

Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats.

PubMed

Kass, P H; Barnes, W G; Spangler, W L; Chomel, B B; Culbertson, M R

1993-08-01

Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D Binding Protein-Macrophage Activating Factor (DBP-maf) Inhibits Angiogenesis and Tumor Growth in Mice1

PubMed Central

Kisker, Oliver; Onizuka, Shinya; Becker, Christian M; Fannon, Michael; Flynn, Evelyn; D'Amato, Robert; Zetter, Bruce; Folkman, Judah; Ray, Rahul; Swamy, Narasimha; Pirie-Shepherd, Steven

2003-01-01

Abstract We have isolated a selectively deglycosylated form of vitamin D binding protein (DBP-maf) generated from systemically available DBP by a human pancreatic cancer cell line. DBP-maf is antiproliferative for endothelial cells and antiangiogenic in the chorioallantoic membrane assay. DBP-maf administered daily was able to potently inhibit the growth of human pancreatic cancer in immune compromised mice (T/C=0.09). At higher doses, DBP-maf caused tumor regression. Histological examination revealed that treated tumors had a higher number of infiltrating macrophages as well as reduced microvessel density, and increased levels of apoptosis relative to untreated tumors. Taken together, these data suggest that DBP-maf is an antiangiogenic molecule that can act directly on endothelium as well as stimulate macrophages to attack both the endothelial and tumor cell compartment of a growing malignancy. PMID:12659668

The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

PubMed

Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

2003-11-01

Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega.

PubMed

Hampel, Verena; Schwarz, Bianca; Kempf, Christine; Köstlin, Roberto; Schillinger, Ulrike; Küchenhoff, Helmut; Fenske, Nora; Brill, Thomas; Hirschberger, Johannes

2007-01-01

Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. Twenty domestic cats. In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.

Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields.

PubMed

Inui, Toshio; Amitani, Haruka; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Mette, Martin

2016-07-01

Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pech, M.; Gazit, A.; Arnstein, P.

1989-04-01

A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potentmore » transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype.« less

Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

PubMed

Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-05-01

Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation.

Near triploidy in a feline fibrosarcoma.

PubMed

Mayr, B; Eschborn, U; Kalat, M

1991-10-01

A seven-year-old male cat developed a subcutaneous fibrosarcoma. The numerical cytogenetic evaluation of the tumour revealed the presence of 69.2% of cells in the near-triploid chromosome range between 51 and 64. The copy numbers of the different chromosomes were widely distributed from monosomies up to heptasomies. Two giant chromosomes were regularly present.

Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats.

PubMed

Rohini, G; Sabitha, K E; Devi, C S Shyamala

2004-08-01

Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.

Effect of alpha-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats.

PubMed

Vasavi, H; Thangaraju, M; Sachdanandam, P

1994-02-23

The anticarcinogenic activity of alpha-tocopherol (Vitamin E) was tried in fibrosarcoma induced rats through its antioxidative potential. The rate of formation of malondialdehyde (MDA), the end product of lipid peroxidation was analysed in alpha-tocopherol (400 mg/kg body weight) treated and untreated fibrosarcoma bearing rats with respective controls. The levels of non-enzymic antioxidants like, glutathione and vitamin E, and enzymic antioxidants viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST) were assayed as well. Significantly increased (p < 0.001) level of lipid peroxide was observed with concomitant decreases in the level of enzymic and non-enzymic antioxidants in fibrosarcoma bearing rats when compared with control animals. In alpha-tocopherol supplemented animals, the corrected level of these parameters were observed likely to near normal values. Thus, alpha-tocopherol can be accepted to pose first line of defense mechanism against excessively formed reactive species due to impaired antioxidant systems in fibrosarcoma conditions, that cause membrane damage leading to deleterious effects.

Dissociation of lipotoxicity and glucotoxicity in a mouse model of obesity associated diabetes: role of forkhead box O1 (FOXO1) in glucose-induced beta cell failure.

PubMed

Kluth, O; Mirhashemi, F; Scherneck, S; Kaiser, D; Kluge, R; Neschen, S; Joost, H-G; Schürmann, A

2011-03-01

Carbohydrate-free diet prevents hyperglycaemia and beta cell destruction in the New Zealand Obese (NZO) mouse model. Here we have used a sequential dietary regimen to dissociate the effects of obesity and hyperglycaemia on beta cell function and integrity, and to study glucose-induced alterations of key transcription factors over 16 days. Mice were rendered obese by feeding a carbohydrate-free diet for 18 weeks. Thereafter, a carbohydrate-containing diet was given. Plasma glucose, plasma insulin and total pancreatic insulin were determined, and forkhead box O1 protein (FOXO1) phosphorylation and the transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 protein (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MAFA) were monitored by immunohistochemistry for 16 days. Dietary carbohydrates produced a rapid and continuous increase in plasma glucose in NZO mice between day 2 and 16 after the dietary challenge. Hyperglycaemia caused a dramatic dephosphorylation of FOXO1 at day 2, followed by a progressive depletion of insulin stores. The loss of beta cells was triggered by apoptosis (detectable at day 8), associated with reduction of crucial transcription factors (PDX1, NKX6.1 and MAFA). Incubation of isolated islets from carbohydrate-restricted NZO mice or MIN6 cells with palmitate and glucose for 48 h resulted in a dephosphorylation of FOXO1 and thymoma viral proto-oncogene 1 (AKT) without changing the protein levels of both proteins. The dietary regimen dissociates the effects of obesity (lipotoxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice. Obese NZO mice are unable to compensate for the carbohydrate challenge by increasing insulin secretion or synthesising adequate amounts of insulin. In response to the hyperglycaemia, FOXO1 is dephosphorylated, leading to reduced levels of beta cell-specific transcription factors and to apoptosis of the cells.

A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.

PubMed

Sugimoto, Kenji; Ohata, Mutsuhiro; Miyoshi, Jun; Ishizaki, Hiroyoshi; Tsuboi, Naotake; Masuda, Akio; Yoshikai, Yasunobu; Takamoto, Masaya; Sugane, Kazuo; Matsuo, Seiichi; Shimada, Yasuhiro; Matsuguchi, Tetsuya

2004-09-01

A serine/threonine protein kinase, Cot/Tpl2, is indispensable for extracellular signal-regulated kinase (ERK) activation and production of TNF-alpha and PGE2 in LPS-stimulated macrophages. We show here that Cot/Tpl2 is also activated by other Toll-like receptor (TLR) ligands. Bacterial DNA rich in the dinucleotide CG (CpG-DNA), unlike LPS or synthetic lipopeptide, activated ERK in a Cot/Tpl2-independent manner. Peritoneal macrophages and bone marrow-derived DCs from Cot/Tpl2-/- mice produced significantly more IL-12 in response to CpG-DNA than those from WT mice. Enhanced IL-12 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, and the elevated IL-12 mRNA level in Cot/Tpl2-/- macrophages is accompanied by decreased amounts of IL-12 repressors, such as c-musculoaponeurotic fibrosarcoma (c-Maf) and GATA sequence in the IL-12 promoter-binding protein (GA-12-binding protein; GAP-12) in the nucleus. Consistently, Cot/Tpl2-/- mice showed Th1-skewed antigen-specific immune responses upon OVA immunization and Leishmania major infection in vivo. These results indicate that Cot/Tpl2 is an important negative regulator of Th1-type adaptive immunity, that it achieves this regulation by inhibiting IL-12 production from accessory cells, and that it might be a potential target molecule in CpG-DNA-guided vaccination.

A validity and reliability study of the Turkish Multidimensional Assessment of Fatigue (MAF) scale in chronic musculoskeletal physical therapy patients.

PubMed

Yildirim, Yücel; Ergin, Gülbin

2013-01-01

Fatigue is primarily a subjective experience and self-report is the most common approach used to measure fatigue. Numerous self-report instruments have been developed to measure fatigue. Unfortunately, each of these measures was tailored for the situation in which fatigue was studied. Therefore, the aim of this study was to determine the reliability and validity of the Turkish language version of the Multidimensional Assessment of Fatigue Scale (MAF-T) in chronic musculoskeletal physical therapy patients. The MAF-T was supplied by the MAPI Research Institute, and 69 chronic musculoskeletal physical therapy patients were evaluated. To validate MAF-T, all participants completed the MAF-T and Short Form-36 (SF-36). The MAF was administered again one week later to assess test-retest reliability. Using Cronbach α, the internal consistency reliability of the MAF-T was 0.90, the Intraclass Correlation Coefficient (ICC) reliability was 0.96. Item-discriminant validity was calculated between r=0.14 and r=0.82. The correlations between the total scores of the MAF-T scale and the subscale scores of SF-36 were negative and significant (p< 0.01). The MAF-T is a valid and reliable scale for assessing fatigue in chronic musculoskeletal physical therapy patients.

[Surgical and chemotherapeutic treatment of fibrosarcoma in a cat].

PubMed

Odendaal, J S; Cronje, J D; Bastianello, S S

1983-09-01

Fibrosarcoma in a cat was repeatedly treated unsuccessfully by surgery and chemotherapy, which included drugs such as amethopterin sodium at very high dosages, vincristine sulphate and doxyrubicine hydrochloride.

MafA is a Key Molecule in Glucose and Energy Balance in the Central Nervous System and Peripheral Organs

PubMed Central

Tsuchiya, Mariko; Tsuchiya, Ken; Yasuda, Kazuki; Fujita, Mikiko; Takinishi, Akira; Furukawa, Maiko; Nitta, Kosaku; Maeda, Atsushi

2011-01-01

MafA is a strong transactivator of insulin in pancreatic β cells. Elucidating the profile of MafA action in organs other than the pancreas is essential. We established an mRNA interference technique that modifies the level of target mRNAs in mice in vivo. After rapidly injecting MafA-siRNA, the resulting changes in the gene profile were analyzed using a microarray system. Significant suppression of the MafA mRNA levels was observed in the pancreas, liver, adipose tissue, and brain of siRNA-injected mice. As we reported previously, the down-regulation of insulin mRNA and adipocytokines was observed in the pancreas, and MafA siRNA caused alterations in the expressions of genes related to lipid metabolism and cell growth in the liver, and the attenuation of cell differentiation in cultured adipocytes. In addition to the effects on these organs, MafA expression was immunohistochemically detected in the brain in our preliminary data, and the expression level in siRNA-treated mice was significantly suppressed. The expressions of the affected genes were distinct, including growth hormone, vasopressin, hypocretin, and pro-melanin-concentrating hormone, were almost completely down-regulated (to ~1/100). These results suggested that MafA is likely involved in the regulation of hormonal systems related to glucose metabolism, and MafA is likely positioned near the beginning of the cascade or may influence the expressions of the above-mentioned genes in coordination with other factors in brain tissue. Taken together, the findings in this study suggested that MafA functions as a transcription factor with distinct activities in each organ and is cross-linked in several organs. PMID:23675216

c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections.

PubMed

Hu, Jia; Huang, Tianwen; Li, Tingting; Guo, Zhen; Cheng, Leping

2012-04-18

Establishment of proper connectivity between peripheral sensory neurons and their central targets is required for an animal to sense and respond to various external stimuli. Dorsal root ganglion (DRG) neurons convey sensory signals of different modalities via their axon projections to distinct laminae in the dorsal horn of the spinal cord. In this study, we found that c-Maf was expressed predominantly in the interneurons of laminae III/IV, which primarily receive inputs from mechanoreceptive DRG neurons. In the DRG, c-Maf⁺ neurons also coexpressed neurofilament-200, a marker for the medium- and large-diameter myelinated afferents that transmit non-noxious information. Furthermore, mouse embryos deficient in c-Maf displayed abnormal development of dorsal horn laminae III/IV neurons, as revealed by the marked reduction in the expression of several marker genes for these neurons, including those for transcription factors MafA and Rora, GABA(A) receptor subunit α5, and neuropeptide cholecystokinin. In addition, among the four major subpopulations of DRG neurons marked by expression of TrkA, TrkB, TrkC, and MafA/GFRα2/Ret, c-Maf was required selectively for the proper differentiation of MafA⁺/Ret⁺/GFRα2⁺ low-threshold mechanoreceptors (LTMs). Last, we found that the central and peripheral projections of mechanoreceptive DRG neurons were compromised in c-Maf deletion mice. Together, our results indicate that c-Maf is required for the proper development of MafA⁺/Ret⁺/GFRα2⁺ LTMs in the DRG, their afferent projections in the dorsal horn and Pacinian corpuscles, as well as neurons in laminae III/IV of the spinal cord.

Electrochemical treatment of mouse and rat fibrosarcomas with direct current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.K.; McDougall, J.A.; Ahn, C.

1997-03-01

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten ratsmore » in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study; i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice, and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.« less

Infantile fibrosarcoma of ethmoid sinus, misdiagnosed as an adenoid in a 5-year-old child

PubMed Central

Geramizadeh, Bita; Khademi, Bijan; Karimi, Mehran; Shekarkhar, Golsa

2015-01-01

Infantile fibrosarcoma of head and neck is rare and the presence of this tumor in ethmoid sinus is even more uncommon. To the best of our knowledge, <5 cases have been reported in the last 20 years in the English literature, so far, only one of which has been infantile type in a 15 months old girl. In this case report, we will explain our experience with a rare case of infantile fibrosarcoma originating from ethmoid sinus in a 5-year-old boy who presented with dyspnea and epistaxis. After biopsy, it was diagnosed as fibrosarcoma of sinus origin. PMID:26604519

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells.

PubMed

Gabryšová, Leona; Alvarez-Martinez, Marisol; Luisier, Raphaëlle; Cox, Luke S; Sodenkamp, Jan; Hosking, Caroline; Pérez-Mazliah, Damián; Whicher, Charlotte; Kannan, Yashaswini; Potempa, Krzysztof; Wu, Xuemei; Bhaw, Leena; Wende, Hagen; Sieweke, Michael H; Elgar, Greg; Wilson, Mark; Briscoe, James; Metzis, Vicki; Langhorne, Jean; Luscombe, Nicholas M; O'Garra, Anne

2018-05-01

The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4 + T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4 + T cells in disease models involving the T H 1 subset of helper T cells (malaria), T H 2 cells (allergy) and T H 17 cells (autoimmunity) in vivo. Although mice with c-Maf deficiency targeted to T cells showed greater pathology in T H 1 and T H 2 responses, T H 17 cell-mediated pathology was reduced in this context, with an accompanying decrease in T H 17 cells and increase in Foxp3 + regulatory T cells. Bivariate genomic footprinting elucidated the c-Maf transcription-factor network, including enhanced activity of NFAT; this led to the identification and validation of c-Maf as a negative regulator of IL-2. The decreased expression of the gene encoding the transcription factor RORγt (Rorc) that resulted from c-Maf deficiency was dependent on IL-2, which explained the in vivo observations. Thus, c-Maf is a positive and negative regulator of the expression of cytokine-encoding genes, with context-specific effects that allow each immune response to occur in a controlled yet effective manner.

Bilateral subcutaneous fibrosarcomas in a cat following feline parvo-, herpes- and calicivirus vaccination.

PubMed

De Man, Marc M G; Ducatelle, Richard V

2007-10-01

A crossbred cat developed a subcutaneous fibrosarcoma on the left side of the thorax at the site of previous administration of a feline parvo-, herpes- and calicivirus vaccine. A few months later the cat developed a second mass on the right side of the thorax after a booster vaccine had been administered at this site. This unique case of bilateral fibrosarcomas in a cat shortly after vaccination with parvo-, herpes- and caliciviruses suggests an individual disposition for the development of vaccine-associated sarcomas and a possible triggering of this type of pathological response which could have precipitated the development of the second tumour. To the authors' knowledge, this is the first case of vaccine-induced fibrosarcomas occurring bilaterally after injection of a feline parvo-, herpes- and calicivirus containing vaccine at different sides of the thorax.

MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth.

PubMed

Blanchi, Bruno; Kelly, Louise M; Viemari, Jean-Charles; Lafon, Isabelle; Burnet, Henri; Bévengut, Michelle; Tillmanns, Silke; Daniel, Laurent; Graf, Thomas; Hilaire, Gerard; Sieweke, Michael H

2003-10-01

The genetic basis for the development of brainstem neurons that generate respiratory rhythm is unknown. Here we show that mice deficient for the transcription factor MafB die from central apnea at birth and are defective for respiratory rhythmogenesis in vitro. MafB is expressed in a subpopulation of neurons in the preBötzinger complex (preBötC), a putative principal site of rhythmogenesis. Brainstems from Mafb(-/-) mice are insensitive to preBötC electrolytic lesion or stimulation and modulation of rhythmogenesis by hypoxia or peptidergic input. Furthermore, in Mafb(-/-) mice the preBötC, but not major neuromodulatory groups, presents severe anatomical defects with loss of cellularity. Our results show an essential role of MafB in central respiratory control, possibly involving the specification of rhythmogenic preBötC neurons.

Case report: A breast cancer patient treated with GcMAF, sonodynamic therapy and hormone therapy.

PubMed

Inui, Toshio; Makita, Kaori; Miura, Hirona; Matsuda, Akiko; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Nishikata, Takahito; Hori, Hitoshi; Sakamoto, Norihiro

2014-08-01

Gc protein-derived macrophage-activating factor (GcMAF) occurs naturally in the human body. It has various functions, such as macrophage activation and antitumor activities. Recently, immunotherapy has become an attractive new strategy in the treatment of cancer. GcMAF-based immunotherapy can be combined with many other therapies. Sonodynamic therapy (SDT) using low-intensity ultrasound is a novel therapeutic modality. Ultrasound has been demonstrated to activate a number of sonosensitive agents allowing for the possibility of non-invasive targeted treatment for both superficial and deep-seated tumors. The current case study demonstrates that GcMAF and SDT can be used in combination with conventional therapies in patients with metastatic cancer, especially where treatment options are limited due to factors such as toxicity. This case study also suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT, to be used in combination with GcMAF immunotherapy as a systemic treatment. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF).

PubMed

Yamamoto, Nobuto; Ushijima, Naofumi; Koga, Yoshihiko

2009-01-01

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of HIV-infected patients was lost or reduced because Gc protein is deglycosylated by alpha-N-acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Since Nagalase is the intrinsic component of the envelope protein gp120, serum Nagalase activity is the sum of enzyme activities carried by both HIV virions and envelope proteins. These Nagalase carriers were already complexed with anti-HIV immunoglobulin G (IgG) but retained Nagalase activity that is required for infectivity. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effects in humans. Macrophages activated by administration of 100 ng GcMAF develop a large amount of Fc-receptors as well as an enormous variation of receptors that recognize IgG-bound and unbound HIV virions. Since latently HIV-infected cells are unstable and constantly release HIV virions, the activated macrophages rapidly intercept the released HIV virions to prevent reinfection resulting in exhaustion of infected cells. After less than 18 weekly administrations of 100 ng GcMAF for nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV-infection, which was also confirmed by no infectious center formation by provirus inducing agent-treated patient PBMCs. No recurrence occurred and their healthy CD + cell counts were maintained for 7 years.

Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

PubMed

Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

2017-12-01

Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT 2 R 2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support, education, and patient

Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia in a cat.

PubMed

Linton, Michael; Tong, Lydia; Simon, Adrian; Buffa, Eugene; McGregor, Ross; Labruyére, Julien; Foster, Darren

2016-01-01

A 14-year-old, female neutered domestic shorthair presented for dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous mass was present within the pericardial sac, and the mass continued caudally with the mesenteric fat. On CT, the outline of the diaphragm was not continuous and there was an obvious defect with diaphragmatic thickening present at the mid-level of the liver. A pleural effusion and a small-volume pericardial effusion were also present. A ventral midline coeliotomy and median sternotomy revealed a 5 × 6 × 7 cm firm, irregular, tan-coloured soft tissue mass within the pericardial sac attached to both the diaphragmatic defect and liver. The mass was carefully dissected away from the heart and the diaphragmatic defect was repaired with primary closure. Postoperatively, the cat had a persistent pneumothorax that required continuous pleural suction for 41 h. The cat died 44 h postoperatively. Histopathology and immunohistochemistry confirmed the mass to be a hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH). This is the first reported case of metaplastic transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic fibrosarcoma is a rarely reported location for fibrosarcoma in this species.

Solid Waste Management in Marine Amphibious Force (MAF) Operations: Analysis and Alternatives.

DTIC Science & Technology

1980-09-01

Experience during the Southeast Asia conflict and elsewhere shows that MAF solid waste management requires a significant deployment of manpower and equipment...MAF varies, by necessity, with the location or type of military action. Based in part on recent experience gained in the Southeast Asia conflict, a...4 1- r 410 0 0 MCD %4 0. 0 0> 0 0 0.Z5 -4 4r44. ,4-14 1 cc U 44 UCI 4 4 0 -401. 4 0 0 U2fl󈧺 $ICɜ 41 *4 0J 4)% 4 4) u ~ .)ails- ii , )4 -4 to 40 be

Characteristics of a Virus Isolated from a Feline Fibrosarcoma

PubMed Central

McKissick, G. E.; Lamont, P. H.

1970-01-01

A virus was isolated from a radioresistant feline fibrosarcoma. It induced multi-nucleated giant-cell formation and lysis in a cell line derived from a canine fibro-sarcoma, which was used to characterize the virus. End-point titrations in these cells required 28 days. The virus was sensitive to ether and heat and was destroyed at pH 3. Replication was not inhibited by 5-bromodeoxyuridine. Electron microscopy revealed assembly by a budding process from the plasma membrane of infected cells. The average diameter of the virion was 106 nm. Intracisternal particles with an average diameter of 45 nm were present within infected cells. In two instances secondary monolayers of feline renal cells underwent morphological transformation after inoculation of the virus. The two strains of transformed cells are now in continuous culture and do not yield infectious virus. Images PMID:4194169

Chromosome rearrangements in canine fibrosarcomas.

PubMed

Sargan, D R; Milne, B S; Hernandez, J Aguirre; O'Brien, P C M; Ferguson-Smith, M A; Hoather, T; Dobson, J M

2005-01-01

We have previously reported the use of six- and seven-color paint sets in the analysis of canine soft tissue sarcomas. Here we combine this technique with flow sorting of translocation chromosomes, reverse painting, and polymerase chain reaction (PCR) analysis of the gene content of the reverse paint in order to provide a more detailed analysis of cytogenetic abnormalities in canine tumors. We examine two fibrosarcomas, both from female Labrador retrievers, and show abnormalities in chromosomes 11 and 30 in both cases. Evidence of involvement of TGFBR1 is presented for one tumor.

Computed tomography characteristics of fibrosarcoma -- a histological subtype of feline injection-site sarcoma.

PubMed

Travetti, Olga; di Giancamillo, Mauro; Stefanello, Damiano; Ferrari, Roberta; Giudice, Chiara; Grieco, Valeria; Saunders, Jimmy H

2013-06-01

Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.

Ocular metastasis of a vaccine-associated fibrosarcoma in a cat.

PubMed

Cohen, M; Sartin, E A; Whitley, E M; Whitley, R D; Smith, A N; Brawner, W R; Henderson, R; Behrend, E N

2003-12-01

A 6-year-old, neutered male domestic shorthair cat was evaluated for a recurrent vaccine-associated fibrosarcoma. The cat had three excisions of the tumour prior to presentation and was referred for radiation therapy. Ten months following treatment with radiation therapy, the cat was presented again for a cloudy appearance to the eye. An exenteration was performed, and biopsy revealed fibrosarcoma. At the same time, two discrete pulmonary nodules were identified on thoracic radiographs. Two doses of doxorubicin (20 mg/m(2)) and cyclophosphamide (100 mg/m(2)) were administered intravenously 3 weeks apart. Despite treatment, the pulmonary nodule doubled in size. This case represents the first antemortem report of ocular metastasis of a vaccine-associated sarcoma and supports the highly aggressive nature of these tumours.

Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia in a cat

PubMed Central

Linton, Michael; Tong, Lydia; Simon, Adrian; Buffa, Eugene; McGregor, Ross; Labruyére, Julien; Foster, Darren

2016-01-01

Case summary A 14-year-old, female neutered domestic shorthair presented for dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous mass was present within the pericardial sac, and the mass continued caudally with the mesenteric fat. On CT, the outline of the diaphragm was not continuous and there was an obvious defect with diaphragmatic thickening present at the mid-level of the liver. A pleural effusion and a small-volume pericardial effusion were also present. A ventral midline coeliotomy and median sternotomy revealed a 5 × 6 × 7 cm firm, irregular, tan-coloured soft tissue mass within the pericardial sac attached to both the diaphragmatic defect and liver. The mass was carefully dissected away from the heart and the diaphragmatic defect was repaired with primary closure. Postoperatively, the cat had a persistent pneumothorax that required continuous pleural suction for 41 h. The cat died 44 h postoperatively. Histopathology and immunohistochemistry confirmed the mass to be a hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH). Relevance and novel information This is the first reported case of metaplastic transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic fibrosarcoma is a rarely reported location for fibrosarcoma in this species. PMID:28491416

Cytogenetic variation between four cases of feline fibrosarcoma.

PubMed

Mayr, B; Bockstahler, B; Loupal, G; Reifinger, M; Schleger, W

1996-11-01

Short term cultures of four feline fibrosarcomas were analysed cytogenetically. There was marked genetic heterogeneity between the four cats, each showing a different clonal abnormality. The aberrations detected were one deleted B2, one marker F1 and two reciprocal translocations, t (A2q; E3q) and t (A1q; B4p).

Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma

PubMed Central

Chakraborty, Biswajit; Pal, Ramkrishna; Ali, Mohammed; Singh, Leichombam Mohindro; Shahidur Rahman, Dewan; Kumar Ghosh, Sujit; Sengupta, Mahuya

2016-01-01

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1–10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA. PMID:25938978

Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

PubMed

Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

2004-01-01

Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

Fibrosarcoma of the eyelid in two sibling Czech wolfdogs

PubMed Central

Nordio, Laura; Fattori, Sabina; Giudice, Chiara

2017-01-01

Most canine tumors of the eyelid are tumors generally encountered in the skin. They are most commonly of epithelial origin and benign. In this report, we describe the cases of two sibling Czech wolfdogs presented, one year apart, with a subcutaneous mass involving the left eyelid. Both lesions were histologically consistent with a diagnosis of subcutaneous fibrosarcoma. Immunohistochemical analyses of the tumors revealed a mild positivity for vimentin and negativity for GFAP, desmin, αSMA, myoglobin, S100, PNL2 and calponin, excluding all differential diagnosis (i.e. peripheral nerve sheath tumor, melanoma, perivascular sarcoma, myofibroblastic sarcoma, rhabdomyosarcoma). To the best of authors’ knowledge, this is the first report of canine eyelid fibrosarcoma. Since this rare tumor has been observed in two full siblings, we could speculate the existence of some genetic predisposition to sarcoma, however the present data did not allow any definite conclusion on the etiopathogenesis or genetic basis of these tumors. PMID:28616389

Low-grade fibrosarcoma of the anterior skull base: endoscopic resection and repair.

PubMed

Kuhn, Frederick A; Javer, Amin R

2003-01-01

Fibrosarcomas of the paranasal sinuses and skull base are uncommon tumors. Traditionally, "open approach" surgery remains the mainstay for treatment of choice for these tumors. A 49-year-old man underwent resection of a right anterior skull base fibrosarcoma using the endoscopic approach. Close follow-up using both endoscopic and imaging methods over a period of four years has revealed a well-healed skull base with no evidence of recurrence. Significant resistance exists at present for such a technique to deal with malignant diseases of the head and neck but results from advanced centers continue to prove that this may be a technique worth mastering and improving on.

Primary intraosseous fibrosarcoma in a cat.

PubMed

Levitt, L; Doige, C E

1989-06-01

A primary intraosseous fibrosarcoma was diagnosed in a 1.5-year-old cat. Clinical signs included nonweight-bearing lameness of the right forelimb and signs of pain on palpation of the right elbow. Radiography of the right elbow revealed a well-circumscribed osteolytic lesion of the olecranon. The right fore-limb was amputated, and histologic examination revealed tumor invasion into local veins and metastasis to the axillary lymph nodes. The cat had no signs of tumor redevelopment or pulmonary metastatic disease one year after amputation.

Fibrosarcoma adjacent to the site of microchip implantation in a cat.

PubMed

Daly, Meighan K; Saba, Corey F; Crochik, Sonia S; Howerth, Elizabeth W; Kosarek, Carrie E; Cornell, Karen K; Roberts, Royce E; Northrup, Nicole C

2008-04-01

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Is chondroitin sulfate responsible for the biological effects attributed to the GC protein-derived Macrophage Activating Factor (GcMAF)?

PubMed

Ruggiero, Marco; Reinwald, Heinz; Pacini, Stefania

2016-09-01

We hypothesize that a plasma glycosaminoglycan, chondroitin sulfate, may be responsible for the biological and clinical effects attributed to the Gc protein-derived Macrophage Activating Factor (GcMAF), a protein that is extracted from human blood. Thus, Gc protein binds chondroitin sulfate on the cell surface and such an interaction may occur also in blood, colostrum and milk. This interpretation would solve the inconsistencies encountered in explaining the effects of GcMAF in vitro and in vivo. According to our model, the Gc protein or the GcMAF bind to chondroitin sulfate both on the cell surface and in bodily fluids, and the resulting multimolecular complexes, under the form of oligomers trigger a transmembrane signal or, alternatively, are internalized and convey the signal directly to the nucleus thus eliciting the diverse biological effects observed for both GcMAF and chondroitin sulfate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic membrane assay.

PubMed

Pacini, Stefania; Morucci, Gabriele; Punzi, Tiziana; Gulisano, Massimo; Ruggiero, Marco

2011-04-01

The effects of Gc protein-derived macrophage-activating factor (GcMAF) have been studied in cancer and other conditions where angiogenesis is deregulated. In this study, we demonstrate for the first time that the mitogenic response of human peripheral blood mononuclear cells (PBMCs) to GcMAF was associated with 3'-5'-cyclic adenosine monophosphate (cAMP) formation. The effect was dose dependent, and maximal stimulation was achieved using 0.1 ng/ml. Heparin inhibited the stimulatory effect of GcMAF on PBMCs. In addition, we demonstrate that GcMAF (1 ng/ml) inhibited prostaglandin E(1)- and human breast cancer cell-stimulated angiogenesis in chick embryo chorionallantoic membrane (CAM) assay. Finally, we tested different GcMAF preparations on CAM, and the assay proved to be a reliable, reproducible and inexpensive method to determine the relative potencies of different preparations and their stability; we observed that storage at room temperature for 15 days decreased GcMAF potency by about 50%. These data could prove useful for upcoming clinical trials on GcMAF.

On the MAF solution of the uniformly lengthening pendulum via change of independent variable in the Bessel's equation

NASA Astrophysics Data System (ADS)

Deniz, Coşkun

Common recipe for the Lengthening Pendulum (LP) involves some change of variables to give a relationship with the Bessel's equation. In this work, semiclassical MAF (Modified Airy Function) solution of the LP is being obtained by first transforming the related Bessel's equation into the normal form via the suggested change of independent variable just as one of our recent work regarding the JWKB solution of the LP in (Deniz, 2017). MAF approximation of the first order Bessel Functions (ν = 1) of both type along with their zeros are being obtained analytically with a very good accuracy as a result of the appropriately chosen associated initial values and they are extended to the neighbouring orders (ν = 0 and 2) by the recursion relations. Although common numerical methods given in the literature require adiabatic LP systems where the lengthening rate is small, MAF solution presented here can safely be used for higher lengthening rates and a criterion for its validity is determined via the use of MAF applicability criterion given in the literature. As a result, the semiclassical MAF method which is normally used for the quantum mechanical and optical waveguide systems is applied to the classical LP system successfully just as our previous work regarding the JWKB solution of the LP. Interestingly, we have very accurate results in the entire domain except for x ≈ 0 .

[Sclerosing epithelioid fibrosarcoma of the paravertebral column. Case report and literature review].

PubMed

Puerta Roldán, Patricia; Rodríguez Rodríguez, Rodrigo; Bagué Rossell, Silvia; de Juan Delago, Manel; Molet Teixidó, Joan

2013-01-01

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of low-grade fibrosarcoma, with specific histological and immunohistochemical features and a poor prognosis. We report a case of SEF of the paravertebral column in a 49-year old male who presented a paraspinal mass with extension into the L4-L5 neural foramen and invasion of the L5 nerve root. Histology of the tumourectomy specimen and its immunohistochemical study led to the diagnosis of SEF. This case was particularly unusual due to its paravertebral column location and, despite its low grade, illustrates the malignant potential of SEF. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

CVMP advice on injection-site fibrosarcomas in cats.

PubMed

2003-03-29

In response to increasing concern, the Committee for Veterinary Medicinal Products (CVMP) has produced this advisory notice for veterinary surgeons on the development in cats of fibrosarcomas at sites of administration of veterinary medicinal products. The advice relates principally, but not exclusively, to the subcutaneous injection of vaccines. The issue is of relevance only to cats and no extrapolation should be made to other species or to man. At the current state of knowledge, it is not possible to provide specific advice on the risk that any product, or any type of product, might represent in terms of inducing a fibrosarcoma at the site of administration. However, following the precautionary principle, the CVMP considers that information on this issue should be made available to veterinary surgeons in order that they can have an informed discussion with owners of the benefits and risks of therapeutic interventions in cats, particularly in relation to vaccination and re-vaccination. The CVMP wishes to emphasise that modern vaccines continue to represent the only safe and effective means of protecting cats against serious infectious diseases and this should be taken fully into account in any discussion between veterinary surgeons and owners of cats.

An LPV Adaptive Observer for Updating a Map Applied to an MAF Sensor in a Diesel Engine

PubMed Central

Liu, Zhiyuan; Wang, Changhui

2015-01-01

In this paper, a new method for mass air flow (MAF) sensor error compensation and an online updating error map (or lookup table) due to installation and aging in a diesel engine is developed. Since the MAF sensor error is dependent on the engine operating point, the error model is represented as a two-dimensional (2D) map with two inputs, fuel mass injection quantity and engine speed. Meanwhile, the 2D map representing the MAF sensor error is described as a piecewise bilinear interpolation model, which can be written as a dot product between the regression vector and parameter vector using a membership function. With the combination of the 2D map regression model and the diesel engine air path system, an LPV adaptive observer with low computational load is designed to estimate states and parameters jointly. The convergence of the proposed algorithm is proven under the conditions of persistent excitation and given inequalities. The observer is validated against the simulation data from engine software enDYNA provided by Tesis. The results demonstrate that the operating point-dependent error of the MAF sensor can be approximated acceptably by the 2D map from the proposed method. PMID:26512675

An LPV Adaptive Observer for Updating a Map Applied to an MAF Sensor in a Diesel Engine.

PubMed

Liu, Zhiyuan; Wang, Changhui

2015-10-23

In this paper, a new method for mass air flow (MAF) sensor error compensation and an online updating error map (or lookup table) due to installation and aging in a diesel engine is developed. Since the MAF sensor error is dependent on the engine operating point, the error model is represented as a two-dimensional (2D) map with two inputs, fuel mass injection quantity and engine speed. Meanwhile, the 2D map representing the MAF sensor error is described as a piecewise bilinear interpolation model, which can be written as a dot product between the regression vector and parameter vector using a membership function. With the combination of the 2D map regression model and the diesel engine air path system, an LPV adaptive observer with low computational load is designed to estimate states and parameters jointly. The convergence of the proposed algorithm is proven under the conditions of persistent excitation and given inequalities. The observer is validated against the simulation data from engine software enDYNA provided by Tesis. The results demonstrate that the operating point-dependent error of the MAF sensor can be approximated acceptably by the 2D map from the proposed method.

Unusual Synchronous Presentation of Maxillary Sinus Fibrosarcoma and Gemistocytic Astrocytoma with a Complication Called Leukocytoclastic Vasculitis: A Case Report

PubMed Central

Cadir, Bilge; Karahan, Nermin; Nasir, Serdar; Aydin, M. Asim; Turkaslan, S. Suha

2009-01-01

Fibrosarcoma of the paranasal sinuses is extremely rare pathology and there is limited report in the literature. We report synchronous presentation of maxillary sinus fibrosarcoma and gemistocytic astrocytoma which is, to our knowledge, unique in the literature. Both tumors metastases to other organ rarely and the metastatic spread of gemistocytic astrocytoma to fibrosarcoma or vice versa have also not been reported in the literature yet. This report discusses the clinical course of the disease, outcome of the treatment approach and survival as well as an unusual occurrence of leukocytoclastic vasculitis during the course of radiotherapy in such unusual presentation. PMID:19756200

Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling.

PubMed

Pacini, Stefania; Morucci, Gabriele; Punzi, Tiziana; Gulisano, Massimo; Ruggiero, Marco; Amato, Marcello; Aterini, Stefano

2012-01-01

In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF). Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms. Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1. Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF.

Tumor-associated erythrocytosis in a dog with nasal fibrosarcoma.

PubMed

Couto, C G; Boudrieau, R J; Zanjani, E D

1989-01-01

Erythrocytosis (hematocrit, 79%) was diagnosed in an 8-year-old, neutered female, mixed-breed dog with an intranasal fibrosarcoma. Both serum and tumor erythropoietin (Ep) activities were elevated, as determined by the polycythemic exhypoxic mouse model, and the Ep activity was neutralized in that model by rabbit anti-Ep antibodies. Tumor resection normalized the hematocrit.

Vaccine-associated fibrosarcoma with keloidal differentiation in a cat.

PubMed

Gumber, Sanjeev; Wakamatsu, Nobuko

2011-09-01

A 6-year-old Domestic Shorthair cat was presented with a history of subcutaneous mass of the lateral left hind limb. The subcutaneous mass developed over a period of approximately 16 months subsequent to administration of Feline leukemia virus vaccines. Based on the histopathological and immunohistochemical examination, the subcutaneous mass was diagnosed as vaccine-associated fibrosarcoma with keloidal differentiation.

Fibrosarcoma of the mandible following supravoltage irradiation. Report of a case.

PubMed

Moloy, P J; Kowal, K A; Siegel, W M

1989-10-01

Supravoltage irradiation is commonly thought not to be carcinogenic. Several recent studies question this concept, as does our case report. A 50-year-old woman with stage 1 squamous carcinoma of the left side of the tongue was treated in 1973 with 73 Gy of supravoltage irradiation. Twelve years later a painful, ulcerated lesion that eventually was shown to be fibrosarcoma developed in the contralateral mandible. The fibrosarcoma in this case fulfills all criteria for diagnosing radiation-induced neoplasia and demonstrates that supravoltage irradiation, like other forms of irradiation, can cause malignancy. The occasional occurrence of sarcoma should be recalled during follow-up of patients treated with supravoltage radiation. Similarly, the possibility of radiation-induced tumors should be considered in planning treatment for younger patients with tumors that can be treated equally well by surgery or irradiation.

Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity.

PubMed

Swamy, N; Ghosh, S; Schneider, G B; Ray, R

2001-01-01

Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal

Psychometric evaluation of the Arabic version of the multidimensional assessment of fatigue scale (MAF) for use in patients with ankylosing spondylitis.

PubMed

Bahouq, Hanane; Rostom, Samira; Bahiri, Rachid; Hakkou, Jinane; Aissaoui, Nawal; Hajjaj-Hassouni, Najia

2012-12-01

Fatigue is a frequent symptom during ankylosing spondylitis (AS) often under estimated which needs to be measured properly with respect to its intensity by appropriate measures, such as the multidimensional assessment of fatigue (MAF). The aims of this study were to translate into the classic Arabic version of the MAF questionnaire and to validate its use for assessing fatigue in Moroccan patients with AS. The MAF contains 16 items with a global fatigue index (IGF). The MAF was translated and back-translated to arabic, pretested and reviewed by a committee following the Guillemin criteria (J Clin Epidemiol 46:1417-1432, 1993). It was then validate on 110 Moroccan patients with AS. Reliability for the 3-day test-retest was assessed using internal consistency by Cronbach's alpha coefficient and the intra-class correlation coefficient (ICC). External construct validity was assessed by correlation with pain, activity of disease and other keys variable. The reproducibility of the 15 items was satisfactory with a kappa statistics of agreement superior to 0.6. The ICC for IGF score reproducibility was good and reached 0.98 (IC 95%, 0.96-0.99). The internal consistency was at 0.991 with Cronbach's alpha coefficient. The construct validity showed a positive correlation between MAF and the axial (r = 0.34) and peripheral (r = 0.32) visual analogical scale, the Bath ankylosing spondylitis disease activity index (BASDAI) (r = 0.77), the first item of BASDAI (r = 0.85), the functional disability by the Bath ankylosing spondylitis functional index (r = 0.64), the erythrocyte sedimentation rate (r = 0.43) and the C reactive protein (r = 0.30) (for all P < 0.001). There was no statistical correlation between MAF and the other variables. The Arabic version of the MAF has good comprehensibility, internal consistency, reliability and validity for the evaluation of Arabic speaking patients with AS.

Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects.

PubMed

Anand, Deepti; Agrawal, Smriti A; Slavotinek, Anne; Lachke, Salil A

2018-04-01

Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in nonocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented. This effort reveals FOXE3, HSF4, MAF, and PITX3 to have 33, 16, 18, and 7 unique causal mutations, respectively. Loss-of-function mutant animals for these genes have served to model the pathobiology of the associated human defects, and we discuss the currently known molecular function of these genes, particularly with emphasis on their role in ocular development. Finally, we make the detailed FOXE3, HSF4, MAF, and PITX3 variant information available in the Leiden Online Variation Database (LOVD) platform at https://www.LOVD.nl/FOXE3, https://www.LOVD.nl/HSF4, https://www.LOVD.nl/MAF, and https://www.LOVD.nl/PITX3. Thus, this article informs on key variants in transcription factor genes linked to cataract, aphakia, corneal opacity, glaucoma, microcornea, microphthalmia, anterior segment mesenchymal dysgenesis, and Ayme-Gripp syndrome, and facilitates their access through Web-based databases. © 2018 Wiley Periodicals, Inc.

Gene expression analysis in zebrafish embryos: a potential approach to predict effect concentrations in the fish early life stage test.

PubMed

Weil, Mirco; Scholz, Stefan; Zimmer, Michaela; Sacher, Frank; Duis, Karen

2009-09-01

Based on the hypothesis that analysis of gene expression could be used to predict chronic fish toxicity, the zebrafish (Danio rerio) embryo test (DarT), developed as a replacement method for the acute fish test, was expanded to a gene expression D. rerio embryo test (Gene-DarT). The effects of 14 substances on lethal and sublethal endpoints of the DarT and on expression of potential marker genes were investigated: the aryl hydrocarbon receptor 2, cytochrome P450 1A (cypla), heat shock protein 70, fizzy-related protein 1, the transcription factors v-maf musculoaponeurotic fibrosarcoma oncogene family protein g (avian) 1 and NF-E2-p45-related factor, and heme oxygenase 1 (hmox1). After exposure of zebrafish embryos for 48 h, differential gene expression was evaluated using reverse transcriptase-polymerase chain reaction, gel electrophoresis, and densitometric analysis of the gels. All tested compounds significantly affected the expression of at least one potential marker gene, with cyp1a and hmox1 being most sensitive. Lowest-observed-effect concentrations (LOECs) for gene expression were below concentrations resulting in 10% lethal effects in the DarT. For 10 (3,4- and 3,5-dichloroaniline, 1,4-dichlorobenzene, 2,4-dinitrophenol, atrazine, parathion-ethyl, chlorotoluron, genistein, 4-nitroquinoline-1-oxide, and cadmium) out of the 14 tested substances, LOEC values derived with the Gene-DarT differ by a factor of less than 10 from LOEC values of fish early life stage tests with zebrafish. For pentachloroaniline and pentachlorobenzene, the Gene-DarT showed a 23- and 153-fold higher sensitivity, respectively, while for lindane, it showed a 13-fold lower sensitivity. For ivermectin, the Gene-DarT was by a factor of more than 1,000 less sensitive than the acute fish test. The results of the present study indicate that gene expression analysis in zebrafish embryos could principally be used to predict effect concentrations in the fish early life stage test.

IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis

PubMed Central

Chang, Kai-Kai; Liu, Li-Bing; Jin, Li-Ping; Zhang, Bing; Mei, Jie; Li, Hui; Wei, Chun-Yan; Zhou, Wen-Jie; Zhu, Xiao-Yong; Shao, Jun; Li, Da-Jin; Li, Ming-Qing

2017-01-01

Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4+ T cells, endometrial CD4+ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10+Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10+Th17 cells. PMID:28300844

Fibrosarcoma arising at the site of a retained surgical sponge in a cat.

PubMed

Haddad, Jamie L; Goldschmidt, Michael H; Patel, Reema T

2010-06-01

An 8-year-old female spayed domestic shorthair cat had an abdominal mass palpated as an incidental finding on physical examination. Cytologic findings in ultrasound-guided fine-needle aspirates of the mass were most compatible with a sarcoma, with abundant mineralized material and mixed inflammation. The mass was removed surgically and on gross examination was white-tan, firm, associated with the mesentery, and when transected contained a gauze sponge in its center. On histopathologic examination, an area of central necrosis with mineralization and numerous refractile fibers consistent with sponge material was surrounded by dense fibrous connective tissue (gossypiboma). Within the connective tissue was a population of highly pleomorphic spindle cells consistent with a fibrosarcoma. Immunohistochemically, most neoplastic cells stained strongly positive for vimentin and a low number of cells were positive for smooth muscle actin. The results were consistent with a fibrosarcoma arising at the site of a retained surgical sponge. At a follow-up visit 2 months postoperatively, ultrasonographic and cytologic evidence of metastasis was found in the spleen and mesentery. To our knowledge, this is the first report of malignant transformation at the site of a retained surgical sponge in a cat and the first report of a fibrosarcoma arising within a gossypiboma in a domestic animal.

The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages.

PubMed

Siniscalco, Dario; Bradstreet, James Jeffrey; Cirillo, Alessandra; Antonucci, Nicola

2014-04-17

Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls. To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods. GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children. This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.

The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages

PubMed Central

2014-01-01

Background Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls. Methods To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods. Results GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children. Conclusions This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism. PMID:24739187

Sinonasal fibrosarcoma: a case report.

PubMed

Plaza, G; Ferrando, J; Pinedo, F

2006-07-01

Sinonasal fibrosarcoma (SFS) is an infrequent malignant neoplasm. It usually presents as other sarcomas in this region, with nasal obstruction and epistaxis. The final diagnosis is based on the histopathology and immunohistochemistry. We report the case of a 58-year-old man with an 8-month history of left proptosis, recurrent epistaxis and nasal obstruction. Nasal endoscopy confirmed a left nasal neoplasia. CT and MRI showed the extension of the neoplasia, occupying the left nasal fossa and ethmoid sinuses, and eroding the medial wall of the orbit. Complete removal was achieved through endoscopic sinus surgery, preserving the orbit. SFS was found on histopathologic examination. After 4 years of follow-up, nasal endoscopy, CT and MRI imaging show no sign of recurrence.

Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf

PubMed Central

Hooper, Kirsten Mary; Kong, Weimin

2017-01-01

Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1. In agreement with the in vivo proinflammatory role of PGE2, here we report for the first time that PGE2 inhibits IL-27-induced differentiation and IL-10 production of murine CD4+CD49b+LAG-3+Foxp3- Tr1 cells. The inhibitory effect of PGE2 was mediated through EP4 receptors and induction of cAMP, leading to a significant reduction in c-Maf expression. Although PGE2 reduced IL-21 production in differentiating Tr1 cells, its inhibitory effect on Tr1 differentiation and c-Maf expression also occurred independent of IL-21 signaling. PGE2 did not affect STAT1/3 activation, AhR expression and only marginally reduced Egr-2/Blimp-1 expression. The effect of PGE2 on CD4+CD49b+LAG-3+ Tr1 differentiation was not associated with either induction of Foxp3 or IL-17 production, suggesting a lack of transdifferentiation into Foxp3+ Treg or effector Th17 cells. We recently reported that PGE2 inhibits the expression and production of IL-27 from activated conventional dendritic cells (cDC) in vivo and in vitro. The present study indicates that PGE2 also reduces murine Tr1 differentiation and function directly by acting on IL-27-differentiating Tr1 cells. Together, the ability of PGE2 to inhibit IL-27 production by cDC, and the direct inhibitory effect on Tr1 differentiation mediated through reduction in c-Maf expression, represent a new mechanistic perspective for the proinflammatory activity of PGE2. PMID:28604806

Inverted papilloma-like sinonasal epithelial hyperplasia, overshadowing underlying sinonasal fibrosarcoma: a diagnostic pitfall.

PubMed

Maly, Alexander; Maly, Bella; Eliashar, Ron; Doviner, Victoria

2006-01-01

Proliferating invaginations of the sinonasal epithelium, simulating inverted papillomas, have been mentioned once in the literature as a reactive phenomenon overlying sinonasal fibrosarcomas. These proliferations may be so marked as to make the distinction from inverted papilloma virtually impossible. The possible result is that the examining pathologist's attention might be drawn exclusively to the epithelial component, thus causing him to overlook, especially in a small biopsy, a rather bland but distinctive sarcomatoid component which is located underneath. We report such a case of marked endophytic proliferation of sinonasal epithelium which was interpreted, in the preoperative biopsy, as an inverted papilloma with dense fibrous stroma which later, in the surgical specimen, was found to be a part of a submucosal fibrosarcoma. The diagnostic pitfall is discussed.

3D chick embryo chorioallantoic membrane model as an in vivo model to study morphological and histopathological features of feline fibrosarcomas.

PubMed

Zabielska-Koczywąs, Katarzyna; Wojtkowska, Agata; Dolka, Izabella; Małek, Anna; Walewska, Magdalena; Wojtalewicz, Anna; Żbikowski, Artur; Lechowski, Roman

2017-06-26

The chick embryo chorioallantoic membrane (CAM) model is well described in human medicine as a cost-effective, easy to perform preclinical oncological model for observing pro- and antiangiogenic response, tumor biology and metastasis. The main objective of this article was to present the modification of the CAM assay in order to evaluate tumor growth from two feline fibrosarcoma cell lines (FFS1, FFS3) and describe their morphological and histopathological features. The authors described morphological and histopathological features of two feline fibrosarcoma cell lines (FFS1 and FFS3) grown on the CAM. Tumors from the FFS1 cell line showed high malignancy (grade III), while tumors from the FFS3 cell line were grade II. Proliferation markers (Ki-67 and PCNA) were determined and the positive correlation between PCNA and tumor grade (r = 0.8247; p < 0.001) was demonstrated, as opposed to Ki-67. The results obtained indicate that PCNA may be helpful to evaluate the tumor grade, better than Ki-67, for feline fibrosarcomas. However, further investigations of proliferation marker, in bigger number of feline spontaneous fibrosarcomas and feline fibrosarcomas grown on the CAM from different cell lines, are needed to confirm these observations.

Myelo-erythroid commitment after burn injury is under β-adrenergic control via MafB regulation.

PubMed

Hasan, Shirin; Johnson, Nicholas B; Mosier, Michael J; Shankar, Ravi; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L; Muthumalaiappan, Kuzhali

2017-03-01

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (lin neg Sca1 + cKit + ), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB + cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients' peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective β1,2-adrenergic blocker) increases MEPs. Also, MafB + cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that β-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients. Copyright © 2017 the American Physiological Society.

Myelo-erythroid commitment after burn injury is under β-adrenergic control via MafB regulation

PubMed Central

Hasan, Shirin; Johnson, Nicholas B.; Mosier, Michael J.; Shankar, Ravi; Conrad, Peggie; Szilagyi, Andrea; Gamelli, Richard L.

2017-01-01

Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (linneg Sca1+cKit+), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). β-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB+ cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients’ peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective β1,2-adrenergic blocker) increases MEPs. Also, MafB+ cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that β-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients. PMID:28031160

Insulin Transactivator MafA Regulates Intrathymic Expression of Insulin and Affects Susceptibility to Type 1 Diabetes

PubMed Central

Noso, Shinsuke; Kataoka, Kohsuke; Kawabata, Yumiko; Babaya, Naru; Hiromine, Yoshihisa; Yamaji, Kaori; Fujisawa, Tomomi; Aramata, Shinsaku; Kudo, Takashi; Takahashi, Satoru; Ikegami, Hiroshi

2010-01-01

OBJECTIVE Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes. RESEARCH DESIGN AND METHODS The expression profiles of transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2 expression and serum autoantibodies were examined in Mafa knockout mice. Luciferase reporter assay was performed for newly identified polymorphisms of mouse Mafa and human MAFA. A case-control study was applied for human MAFA polymorphisms. RESULTS Mafa, Ins2, and Aire expression was detected in the thymus. Mafa expression was lower in NOD thymus than in the control and was correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2 expression and induced autoantibodies against pancreatic islets. Functional polymorphisms of MafA were newly identified in NOD mice and humans, and polymorphisms of human MAFA were associated with susceptibility to type 1 diabetes but not to autoimmune thyroid disease. CONCLUSIONS These data indicate that functional polymorphisms of MafA are associated with reduced expression of insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as well as human type 1 diabetes. PMID:20682694

High superficial musculoaponeurotic system facelift with finger-assisted facial spaces dissection for Asian patients.

PubMed

Ryu, Min-Hee; Moon, Victor A

2015-01-01

Few facelift methods are designed specifically for Asian patients. Because of their characteristic thick skin and flat, wide facial geometry, satisfactory facelift results can be difficult to achieve in these patients. The authors evaluated outcomes achieved with a high superficial musculoaponeurotic system (high-SMAS) facelift with finger-assisted facial spaces dissection to rejuvenate the aging Asian face. Fifty-three patients underwent this facelift procedure. The indication for surgery was typical sagging of the face associated with aging; the relative contraindications were previous facelift and severe facial atrophy. Mean patient age was 50.7 years. Patients received follow-up for a mean of 19 months. In all cases, improvement was seen in soft-tissue sagging of the midface and lower face. One patient experienced unilateral temporal nerve injury, 3 experienced hematoma, and 2 had wound dehiscence. Understanding surgical anatomy including facial layers, spaces, and retaining ligaments is crucial for stable application of facelift techniques in Asian patients. Because of the small number of patients evaluated in this study and the limited follow-up period, more research is needed to define suitable facelift methods for these patients. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

PubMed Central

Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

2004-01-01

Background In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. Methods BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 106 and 1 × 105 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Results Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

PubMed

Church, Alanna J; Calicchio, Monica L; Nardi, Valentina; Skalova, Alena; Pinto, Andre; Dillon, Deborah A; Gomez-Fernandez, Carmen R; Manoj, Namitha; Haimes, Josh D; Stahl, Joshua A; Dela Cruz, Filemon S; Tannenbaum-Dvir, Sarah; Glade-Bender, Julia L; Kung, Andrew L; DuBois, Steven G; Kozakewich, Harry P; Janeway, Katherine A; Perez-Atayde, Antonio R; Harris, Marian H

2018-03-01

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation

PubMed Central

Nishikawa, Keizo; Nakashima, Tomoki; Takeda, Shu; Isogai, Masashi; Hamada, Michito; Kimura, Ayako; Kodama, Tatsuhiko; Yamaguchi, Akira; Owen, Michael J.; Takahashi, Satoru; Takayanagi, Hiroshi

2010-01-01

Aging leads to the disruption of the homeostatic balance of multiple biological systems. In bone marrow multipotent mesenchymal cells undergo differentiation into various anchorage-dependent cell types, including osteoblasts and adipocytes. With age as well as with treatment of antidiabetic drugs such as thiazolidinediones, mesenchymal cells favor differentiation into adipocytes, resulting in an increased number of adipocytes and a decreased number of osteoblasts, causing osteoporosis. The mechanism behind this differentiation switch is unknown. Here we show an age-related decrease in the expression of Maf in mouse mesenchymal cells, which regulated mesenchymal cell bifurcation into osteoblasts and adipocytes by cooperating with the osteogenic transcription factor Runx2 and inhibiting the expression of the adipogenic transcription factor Pparg. The crucial role of Maf in both osteogenesis and adipogenesis was underscored by in vivo observations of delayed bone formation in perinatal Maf–/– mice and an accelerated formation of fatty marrow associated with bone loss in aged Maf+/– mice. This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases. PMID:20877012

WE-G-204-05: Relative Object Detectability Evaluation of a New High Resolution A-Se Direct Detection System Compared to Indirect Micro-Angiographic Fluoroscopic (MAF) Detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russ, M; Nagesh, S Setlur; Ionita, C

2015-06-15

Purpose: To evaluate the task specific imaging performance of a new 25µm pixel pitch, 1000µm thick amorphous selenium direct detection system with CMOS readout for typical angiographic exposure parameters using the relative object detectability (ROD) metric. Methods: The ROD metric uses a simulated object function weighted at each spatial frequency by the detectors’ detective quantum efficiency (DQE), which is an intrinsic performance metric. For this study, the simulated objects were aluminum spheres of varying diameter (0.05–0.6mm). The weighted object function is then integrated over the full range of detectable frequencies inherent to each detector, and a ratio is taken ofmore » the resulting value for two detectors. The DQE for the 25µm detector was obtained from a simulation of a proposed a-Se detector using an exposure of 200µR for a 50keV x-ray beam. This a-Se detector was compared to two microangiographic fluoroscope (MAF) detectors [the MAF-CCD with pixel size of 35µm and Nyquist frequency of 14.2 cycles/mm and the MAF-CMOS with pixel size of 75µm and Nyquist frequency of 6.6 cycles/mm] and a standard flat-panel detector (FPD with pixel size of 194µm and Nyquist frequency of 2.5cycles/mm). Results: ROD calculations indicated vastly superior performance by the a-Se detector in imaging small aluminum spheres. For the 50µm diameter sphere, the ROD values for the a-Se detector compared to the MAF-CCD, the MAF-CMOS, and the FPD were 7.3, 9.3 and 58, respectively. Detector performance in the low frequency regime was dictated by each detector’s DQE(0) value. Conclusion: The a-Se with CMOS readout is unique and appears to have distinctive advantages of incomparable high resolution, low noise, no readout lag, and expandable design. The a-Se direct detection system will be a powerful imaging tool in angiography, with potential break-through applications in diagnosis and treatment of neuro-vascular disease. Supported by NIH Grant: 2R01EB002873 and an

Endocardial fibrosarcoma in a reticulated python (Python reticularis).

PubMed

Gumber, Sanjeev; Nevarez, Javier G; Cho, Doo-Youn

2010-11-01

A female, reticulated python (Python reticularis) of unknown age was presented with a history of lethargy, weakness, and distended coelom. Physical examination revealed severe dystocia and stomatitis. The reticulated python was euthanized due to a poor clinical prognosis. Postmortem examination revealed marked distention of the reproductive tract with 26 eggs (10-12 cm in diameter), pericardial effusion, and a slightly firm, pale tan mass (3-4 cm in diameter) adhered to the endocardium at the base of aorta. Based on histopathologic and transmission electron microscopic findings, the diagnosis of endocardial fibrosarcoma was made.

Derivation of feline vaccine-associated fibrosarcoma cell line and its growth on chick embryo chorioallantoic membrane - a new in vivo model for veterinary oncological studies.

PubMed

Zabielska, K; Lechowski, R; Król, M; Pawłowski, K M; Motyl, T; Dolka, I; Zbikowski, A

2012-12-01

Feline vaccine associated fibrosarcomas are the second most common skin tumor in cats. Methods of treatment are: surgery, chemotherapy and radiotherapy. Nevertheless, the usage of cytostatics in feline vaccine associated sarcoma therapy is limited due to their adverse side effects, high toxicity and low biodistribution after i.v. injection. Therefore, much research on new therapeutic drugs is being conducted. In human medicine, the chick embryo chorioallantoic membrane (CAM) model is used as a cheap and easy to perform assay to assess new drug effectiveness in cancer treatment. Various human cell lines have different tumors growth on CAM. In veterinary medicine such model has not been described yet. In the present article derivation of feline vaccine associated fibrosarcoma cell line and its growth on CAM is described. The cell line and the tumor grown were confirmed by histopathological and immunohistochemical examination. As far as we believe, this is the first attempt to create such model, which may be used for further in vivo studies in veterinary oncology.

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma).

PubMed

Fu, Y S; Perzin, K H

1976-06-01

In a study of 256 nonepithelial neoplasms involving the nasal cavity, paranasal sinuses, and nasopharynx, 23 lesions were classified as fibrous tissue tumors, including four cases of "fibroma", six of fibromatosis, and thirteen of fibrosarcoma. The clinical findings associated with these lesions are described, their histologic features illustrated, results of therapy presented and clinicopathologic correlations made. The "fibromas" presented a small localized nodules. None recurred after local excision. Fibromatosis, a locally aggressive tumor, does not metastasize, but may cause considerable morbidity or even death due to local infiltration which may be difficult to control surgically. Fibrosarcoma may cause death either by local infiltration or by metastasis, but has a better prognosis than most other sarcomas of this region. We recommend that a large en block resection be performed initially for fibromatosis and fibrosarcoma growing in this area, after the diagnosis has been made by biopsy. In this series, including patients who had more than one operation, recurrent tumor was seen following 10 of 12 limited local excisions performed for fibromatosis and fibrosarcoma, but in only one of 13 patients after a large bloc resection. The problems involved in histologically differentiating fibrous tissue tumors from other lesions are discussed. A patient with the rare syndrome of multicentric fibromatosis with spontaneous regression of lesions is presented.

The nature of immunity to Snyder-Theilen fibrosarcoma virus induced tumors in cats.

PubMed

Johnson, L; Pedersen, N C; Theilen, G H

1985-07-01

Snyder-Theilen fibrosarcoma virus (ST-FeSV) induced tumors evoked a vigorous immune response in adolescent cats. The response was characterized histologically by a lymphoid and histiocytic cell infiltrate beginning around the 9th day post inoculation. Hyperemia edema, hemorrhage, and necrosis of the tumors occurred shortly thereafter. Gross regression of the tumors commenced around the 15th day. Viable fibrosarcoma cells could be recovered as almost pure cultures from tumors biopsied on the 9th day. Biopsies taken between days 9 and 15 contained progressively fewer tumor cells and increasing numbers of lymphoid cells, histiocytes, giant cells, and normal fibroblasts. Tumor cells in such mixed cultures did not replicate as fast as normal and died out within 7 to 14 days. Viable tumor cells were not recovered from biopsies taken after day 15. Fibrosarcoma regression was associated with the appearance of tumor cell specific cytotoxic lymphocytes and antibodies in the blood. Cell mediated immunity, as determined by a chromium release assay, consisted of both antibody dependent and independent mechanisms. Fluorescent and complement dependent cytolytic antibodies were detected in the blood at the same time as cytotoxic lymphocytes, but persisted after regression. In a preliminary experiment, serum from tumor regressor cats was injected into susceptible kittens, and the kittens were then challenged with ST-FeSV transformed fibroblasts or whole FeSV. Immune serum did not prevent the appearance of initial growth of tumors, but did slow their subsequent growth and increased the rate of regression. Immune serum had a much more dramatic inhibitory effect on the accompanying retrovirus infection.

c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont.

PubMed

Xu, Mo; Pokrovskii, Maria; Ding, Yi; Yi, Ren; Au, Christy; Harrison, Oliver J; Galan, Carolina; Belkaid, Yasmine; Bonneau, Richard; Littman, Dan R

2018-02-15

Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt + FOXP3 + regulatory T (iT reg ) cells that selectively restrain pro-inflammatory T helper 17 (T H 17) cells and whose function is dependent on the transcription factor c-MAF. Whereas colonization of wild-type mice by H. hepaticus promoted differentiation of RORγt-expressing microorganism-specific iT reg cells in the large intestine, in disease-susceptible IL-10-deficient mice, there was instead expansion of colitogenic T H 17 cells. Inactivation of c-MAF in the T reg cell compartment impaired differentiation and function, including IL-10 production, of bacteria-specific iT reg cells, and resulted in the accumulation of H. hepaticus-specific inflammatory T H 17 cells and spontaneous colitis. By contrast, RORγt inactivation in T reg cells had only a minor effect on the bacteria-specific T reg and T H 17 cell balance, and did not result in inflammation. Our results suggest that pathobiont-dependent inflammatory bowel disease is driven by microbiota-reactive T cells that have escaped this c-MAF-dependent mechanism of iT reg -T H 17 homeostasis.

Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism.

PubMed

Cui, Kai; Zhang, Shaobo; Jiang, Xin; Xie, Weidong

2016-06-01

The present study investigated the synergic effects and potential mechanisms of action of Astragalus polysaccharides (APS) combined with Crataegus flavonoids (CF) in the treatment of type 1 diabetes. Diabetes was induced by intraperitoneal injection of 100 mg/kg streptozotocin in mice. Normal and untreated diabetic control mice were used, and CF‑treated (200 mg/kg/day), APS‑treated (200 mg/kg/day), APS + CF (AC)‑treated (200 mg/kg/day of each) and metformin‑treated (200 mg/kg/day) diabetic mice were orally administrated the appropriate therapeutic agent for 4 weeks. The results demonstrated that AC treatment significantly reduced the fasting blood glucose, food and water intake in the diabetic mice. The AC group demonstrated increased serum insulin levels and islet cell function was restored. Furthermore, the AC‑treated mice demonstrated significant increases in the protein expression levels of pancreatic and duodenal homeobox‑1 and phosphorylated adenosine 5'‑monophosphate‑activated protein kinase in the pancreatic and liver tissue samples, respectively. In addition, AC significantly increased the mRNA expression levels of neurogenin 3, v‑maf musculoaponeurotic fibrosarcoma oncogene family, protein A and insulin, and simultaneously decreased the expressions of interleukin 6, tumor necrosis factor‑α and chemokine (C‑C motif) ligand 2 in the pancreatic islet cells of diabetic mice. The anti‑inflammatory activity of APS and the islet‑restoring effect of CF may contribute to the improvement of islet function. AC exerted greater antidiabetic effects compared with APS or CF treatments alone. These results indicated that AC treatment had a synergic antidiabetic effect, which may involve improvements in islet function and liver metabolism. These effects of AC may facilitate the treatment of type 1 or 2 diabetes, as these patients frequently experience impaired islet function and disordered extrapancreatic metabolism.

SU-E-I-53: Comparison of Kerma-Area-Product Between the Micro-Angiographic Fluoroscope (MAF) and a Flat Panel Detector (FPD) as Used in Neuro-Endovascular Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijayan, S; Rana, V; Nagesh, S Setlur

Purpose: To determine the reduction of integral dose to the patient when using the micro-angiographic fluoroscope (MAF) compared to when using the standard flat-panel detector (FPD) for the techniques used during neurointerventional procedures. Methods: The MAF is a small field-of-view, high resolution x-ray detector which captures 1024 x 1024 pixels with an effective pixel size of 35μm and is capable of real-time imaging up to 30 frames per second. The MAF was used in neuro-interventions during those parts of the procedure when high resolution was needed and the FPD was used otherwise. The technique parameters were recorded when each detectormore » was used and the kerma-area-product (KAP) per image frame was determined. KAP values were calculated for seven neuro interventions using premeasured calibration files of output as a function of kVp and beam filtration and included the attenuation of the patient table for the frontal projections to be more representative of integral patient dose. The air kerma at the patient entrance was multiplied by the beam area at that point to obtain the KAP values. The ranges of KAP values per frame were determined for the range of technique parameters used during the clinical procedures. To appreciate the benefit of the higher MAF resolution in the region of interventional activity, DA technique parameters were generally used with the MAF. Results: The lowest and highest values of KAP per frame for the MAF in DA mode were 4 and 50 times lower, respectively, compared to those of the FPD in pulsed fluoroscopy mode. Conclusion: The MAF was used in those parts of the clinical procedures when high resolution and image quality was essential. The integral patient dose as represented by the KAP value was substantially lower when using the MAF than when using the FPD due to the much smaller volume of tissue irradiated. This research was supported in part by Toshiba Medical Systems Corporation and NIH Grant R01EB002873.« less

Microchip-associated fibrosarcoma in a cat.

PubMed

Carminato, Antonio; Vascellari, Marta; Marchioro, Wendy; Melchiotti, Erica; Mutinelli, Franco

2011-12-01

A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccination guidelines, avoiding the interscapular area, enabled confirmation of the definitive aetiology of the neoplasia. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

A combined approach based on MAF analysis and AHP method to fault detection mapping: A case study from a gas field, southwest of Iran

NASA Astrophysics Data System (ADS)

Shakiba, Sima; Asghari, Omid; Khah, Nasser Keshavarz Faraj

2018-01-01

A combined geostatitical methodology based on Min/Max Auto-correlation Factor (MAF) analysis and Analytical Hierarchy Process (AHP) is presented to generate a suitable Fault Detection Map (FDM) through seismic attributes. Five seismic attributes derived from a 2D time slice obtained from data related to a gas field located in southwest of Iran are used including instantaneous amplitude, similarity, energy, frequency, and Fault Enhancement Filter (FEF). The MAF analysis is implemented to reduce dimension of input variables, and then AHP method is applied on three obtained de-correlated MAF factors as evidential layer. Three Decision Makers (DMs) are used to construct PCMs for determining weights of selected evidential layer. Finally, weights obtained by AHP were multiplied in normalized valued of each alternative (MAF layers) and the concluded weighted layers were integrated in order to prepare final FDM. Results proved that applying algorithm proposed in this study generate a map more acceptable than the each individual attribute and sharpen the non-surface discontinuities as well as enhancing continuity of detected faults.

Near-infrared optical guided surgery of highly infiltrative fibrosarcomas in cats using an anti-αvß3 integrin molecular probe.

PubMed

Wenk, Christiane H F; Ponce, Frédérique; Guillermet, Stéphanie; Tenaud, Corinne; Boturyn, Didier; Dumy, Pascal; Watrelot-Virieux, Dorothée; Carozzo, Claude; Josserand, Véronique; Coll, Jean-Luc

2013-07-01

We investigated how near-infrared imaging could improve highly infiltrative spontaneous fibrosarcoma surgery in 12 cats in a clinical veterinary phase. We used an RGD-based nanoprobe at different doses and times before surgery and a portable clinical grade imaging system. All tumours were labelled by the tracer and had an overall tumour-to-healthy tissue ratio of 14±1 during surgery. No false negatives were found, and the percentage of tumour cells was linearly correlated with the fluorescence intensity. All cats recovered well and were submitted to long-term follow-up that is currently on-going 1year after the beginning of the study. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice.

PubMed

Tabari, M Abouhosseini; Ebrahimpour, S

2014-01-01

Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.

Evaluation and Comparison of High-Resolution (HR) and High-Light (HL) Phosphors in the Micro-Angiographic Fluoroscope (MAF) using Generalized Linear Systems Analyses (GMTF, GDQE) that include the Effect of Scatter, Magnification and Detector Characteristics.

PubMed

Gupta, Sandesh K; Jain, Amit; Bednarek, Daniel R; Rudin, Stephen

2011-01-01

In this study, we evaluated the imaging characteristics of the high-resolution, high-sensitivity micro-angiographic fluoroscope (MAF) with 35-micron pixel-pitch when used with different commercially-available 300 micron thick phosphors: the high resolution (HR) and high light (HL) from Hamamatsu. The purpose of this evaluation was to see if the HL phosphor with its higher screen efficiency could be replaced with the HR phosphor to achieve improved resolution without an increase in noise resulting from the HR's decreased light-photon yield. We designated the detectors MAF-HR and MAF-HL and compared them with a standard flat panel detector (FPD) (194 micron pixel pitch and 600 micron thick CsI(Tl)). For this comparison, we used the generalized linear-system metrics of GMTF, GNNPS and GDQE which are more realistic measures of total system performance since they include the effect of scattered radiation, focal spot distribution, and geometric un-sharpness. Magnifications (1.05-1.15) and scatter fractions (0.28 and 0.33) characteristic of a standard head phantom were used. The MAF-HR performed significantly better than the MAF-HL at high spatial frequencies. The ratio of GMTF and GDQE of the MAF-HR compared to the MAF-HL at 3(6) cycles/mm was 1.45(2.42) and 1.23(2.89), respectively. Despite significant degradation by inclusion of scatter and object magnification, both MAF-HR and MAF-HL provide superior performance over the FPD at higher spatial frequencies with similar performance up to the FPD's Nyquist frequency of 2.5 cycles/mm. Both substantially higher resolution and improved GDQE can be achieved with the MAF using the HR phosphor instead of the HL phosphor.

Suppression of human fibrosarcoma cell growth by transcription factor, Egr-1, involves down-regulation of Bcl-2.

PubMed

Huang, R P; Fan, Y; Peng, A; Zeng, Z L; Reed, J C; Adamson, E D; Boynton, A L

1998-09-11

Previously, we showed that the transcription factor Egr-1 suppressed the proliferation of v-sis transformed NIH3T3 cells and also a number of human tumor cells. Here, we investigate the possible mechanisms responsible for this function. We show that transfected Egr-1 in human fibrosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CAT transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpression of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell proliferation in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Egr-1 may be at least partially mediated through the down-regulation of Bcl-2.

[Fibrosarcoma of the nasal surface in a cat--cosmetically pleasing healing after surgical removal].

PubMed

Neumann, W; Wittker, J; Bahnemann, R

1990-06-01

In a seven year old male domestic cat diagnosis, therapy and healing of a nasal fibrosarcoma is described. After two surgical treatments no recurrence was seen in a time period of 10 months. Even with this unfavourable localization of the tumor a functionally and cosmetically satisfactory result was achieved.

Effects of vitamin D binding protein-macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations.

PubMed

Schneider, G B; Benis, K A; Flay, N W; Ireland, R A; Popoff, S N

1995-06-01

Osteopetrosis is a heterogeneous group of bone diseases characterized by an excess accumulation of bone and a variety of immune defects. Osteopetrosis (op) and incisors absent (ia) are two nonallelic mutations in the rat which demonstrated these skeletal defects as a result of reduced bone resorption. Osteopetrotic (op) rats have severe sclerosis as a result of reduced numbers of osteoclasts which are structurally abnormal. The sclerosis in ia rats is not as severe as in op mutants; they have elevated numbers of osteoclasts, but they are also morphologically abnormal, lacking a ruffled border. Both of these mutations have defects in the inflammation-primed activation of macrophages. They demonstrate independent defects in the cascade involved in the conversion of vitamin D binding protein (DBP) to a potent macrophage activating factor (DBP-MAF). Because this factor may also play a role in the pathogenesis of osteoclastic dysfunction, the effects of ex vivo-generated DBP-MAF were evaluated on the skeletal system of these two mutations. Newborn ia and op rats and normal littermate controls were injected with DBP-MAF or vehicle once every 4 days from birth until 2 weeks of age, at which time bone samples were collected to evaluate a number of skeletal parameters. DBP-MAF treated op rats had an increased number of osteoclasts and the majority of them exhibited normal structure. There was also reduced bone volume in the treated op animals and an associated increased cellularity of the marrow spaces. The skeletal sclerosis was also corrected in the ia rats; the bone marrow cavity size was significantly enlarged and the majority of the osteoclasts appeared normal with extensive ruffled borders.

Fibrosarcoma in the distal radius and carpus of a four-year-old Persian.

PubMed

Cook, J L; Turk, J R; Tomlinson, J L; Corwin, L A; Shaw, D C

1998-01-01

A four-year-old Persian was presented for evaluation of a nonweight-bearing, left forelimb lameness. Radioulnar and pancarpal osteolysis with minimal periosteal reaction were seen on radiographs of the antebrachium. Cytological examinations of fine-needle aspirates and impression smears were suggestive of sarcoma. After forequarter amputation, histopathological examination provided a diagnosis of fibrosarcoma with axillary lymph-node metastasis.

Primary fibrosarcoma of the urinary bladder in a cat: follow-up after incomplete surgical excision.

PubMed

Greci, Valentina; Rocchi, Paola M; Sontuoso, Antonio F; Olivero, Daniela; Capasso, Angelo; Raiano, Vera

2017-01-01

An 11-year-old female spayed domestic shorthair cat was presented with haematuria of 2 months' duration followed by pollakiuria and stranguria. A firm, non-painful mass in the urinary bladder was palpated. Abdominal radiographs and ultrasound were suggestive of a urinary neoplasia. During explorative laparotomy, a partial cystectomy and surgical debulking were performed. Histopathology and immunostaining were consistent with a fibrosarcoma. The cat was discharged 10 days after surgery with a residual mass of about 1.8 cm on ultrasound re-examination. The cat was not given adjuvant therapy. The cat was euthanased 8 months after surgery because of tumour invasion of the urinary trigone and subsequent ureter dilation, hydronephrosis and severe azotaemia. Malignant urinary fibrosarcoma in this cat appeared to be only locally invasive. Palliative surgery without adjuvant postoperative chemotherapy in this cat resulted in an 8 month period of good quality of life.

Caffeine induces metformin anticancer effect on fibrosarcoma in hamsters.

PubMed

Popović, D J; Lalošević, D; Miljković, D; Popović, K J; Čapo, I; Popović, J K

2018-04-01

We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test. The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity. Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

PubMed

Marini, F C; Cannon, J P; Belmont, J W; Shillitoe, E J; Lapeyre, J N

1995-09-01

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

Primary fibrosarcoma of the urinary bladder in a cat: follow-up after incomplete surgical excision

PubMed Central

Greci, Valentina; Rocchi, Paola M; Sontuoso, Antonio F; Olivero, Daniela; Capasso, Angelo; Raiano, Vera

2017-01-01

Case summary An 11-year-old female spayed domestic shorthair cat was presented with haematuria of 2 months’ duration followed by pollakiuria and stranguria. A firm, non-painful mass in the urinary bladder was palpated. Abdominal radiographs and ultrasound were suggestive of a urinary neoplasia. During explorative laparotomy, a partial cystectomy and surgical debulking were performed. Histopathology and immunostaining were consistent with a fibrosarcoma. The cat was discharged 10 days after surgery with a residual mass of about 1.8 cm on ultrasound re-examination. The cat was not given adjuvant therapy. The cat was euthanased 8 months after surgery because of tumour invasion of the urinary trigone and subsequent ureter dilation, hydronephrosis and severe azotaemia. Relevance and novel information Malignant urinary fibrosarcoma in this cat appeared to be only locally invasive. Palliative surgery without adjuvant postoperative chemotherapy in this cat resulted in an 8 month period of good quality of life. PMID:28680699

Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat.

PubMed

Barrett, P M; Merideth, R E; Alarcon, F L

1995-01-01

A 12-year-old, castrated male, domestic shorthair cat with a previous penetrating trauma to the left globe which progressed to a phthisical eye presented for acute blindness. Ophthalmic examination and electroretinography of the right eye were found to be normal. Following euthanasia, gross and microscopic examinations were completed. A left intraocular, posttraumatic fibrosarcoma with extension to the optic nerve and chiasm and induced right optic nerve fiber degeneration at the optic chiasm with necrosis leading to central amaurosis were diagnosed.

Measurement of differences in pO2 in response to perfluorocarbon/carbogen in FSa and NFSa murine fibrosarcomas with low-frequency electron paramagnetic resonance oximetry.

PubMed

Halpern, H J; Yu, C; Peric, M; Barth, E D; Karczmar, G S; River, J N; Grdina, D J; Teicher, B A

1996-05-01

We have used very low-frequency electron paramagnetic resonance (EPR) oximetry to measure the change in oxygen concentration (delta pO2) due to change in breathing atmosphere in FSa and NFSa fibrosarcomas implanted in the legs of C3H mice infused with perfluoro-octylbromine (PFOB). Measurements in each tumor were made before and after the administration of the high-density (47% v/v) perfluorocarbon PFOB, perflubron (Alliance Pharmaceutical Corporation, San Diego, CA). Measurements in each tumor were also made, after the administration of the PFOB, both before (PFOB/air) and after the administration of carbogen (95% O2 + 5% CO2, PFOB/carbogen). Large changes (delta p02) relative to PFOB/air oxygenation were seen with the administration of PFOB/carbogen. No significant difference in oxygen concentration was seen between air-breathing mice with and without PFOB. The mean delta pO2 for FSa tumors was 13 +/- 6 torr, while the mean for NFSa fibrosarcomas was 28 +/- 7 torr. There were such large intertumor differences that the trend toward a smaller change in the more hypoxic FSa tumors was not significant (P = 0.13). This paper describes a novel method of measuring differences in oxygenation in tumor tissues. The results of such measurements indicate large differences in pO2 response to different breathing atmospheres in PFOB-infused tumors of similar histology. The intertumor delta pO2 differences may correlate with differences in radiation response.

77 FR 66794 - Proposed Information Collection; Comment Request; Generic Clearance for Master Address File (MAF...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... to measure the quality of the MAF. Test 22 is currently a one-time project scheduled for fiscal year... designed to be kept up-to-date, thereby eliminating the need to develop a completely new address list for future censuses and surveys. The Census Bureau plans to use the MTdb [[Page 66795

Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside

PubMed Central

Saburi, Ehsan; Saburi, Amin; Ghanei, Mostafa

2017-01-01

Immunotherapy has been used for years in many types of cancer therapy. Recently, cancer immunotherapy has focused on mechanisms which can enhance the development of cell-mediated immunity. Anticancer medications are administered to inhibit immunosuppressive factors such as nagalase enzyme, which is produced by neoplastic cells and destroys macrophage activating factor (Gc-MAF). Anti-neoplastics medications can also enhance immune-cell activity against tumors. Such medications show great potential in cancer immunotherapy using natural human mechanisms against neoplasms. PMID:29201312

Trisomy D1, marker F1: new cytogenetic findings in two cases of feline fibrosarcoma.

PubMed

Mayr, B; Hofstadler, E; Schleger, W; Reifinger, M; Eisenmenger, E

1994-04-01

An 11-year-old female cat and a 12-year-old male cat developed fibrosarcomas. Trisomy D1 was observed in a high percentage (20%) of the tumour cells of the female patient while a large marker chromosome F1 was present in 25% of the tumour cells of the male patient.

Development of the platysma muscle and the superficial musculoaponeurotic system (human specimens at 8-17 weeks of development).

PubMed

De la Cuadra-Blanco, C; Peces-Peña, M D; Carvallo-de Moraes, L O; Herrera-Lara, M E; Mérida-Velasco, J R

2013-01-01

There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8-17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.

SU-E-I-26: Estimation of Micro-Angiographic Fluoroscope (MAF) Gain Settings for Digital Subtraction Angiography (DSA) Based on the Fluoroscopic Exposure.

PubMed

Ionita, C; Loughran, B; Nagesh, S Setlur; Jain, A; Bednarek, D; Rudin, S

2012-06-01

The MAF is a new high-resolution detector which is being clinically evaluated in neuro-vascular procedures. The detector contains a large-dynamic-range, high-sensitivity light image intensifier with variable gain. Since the MAF is a research prototype only partially integrated with the clinical system, x-ray technique parameters must be set manually. To improve workflow we developed an automatic method to estimate and set the proper LII voltage (MAF gain) for DSA acquisition based on the fluoroscopic parameters. The detector entrance exposure (XD) can be written as the x-ray tube output exposure (Xo) times an object attenuation factor and an inverse-square correction. If the object attenuation, scatter and distances are unchanged and the effect of x-ray kVp changes are neglected, then the DSA XD can be expressed as the ratio of Xo(DSA)/Xo(Fluoroscopy) multiplied with XD(fluoroscopy). We measured Xo for fluoroscopy and DSA for mAs and kVp ranges appropriate to neuro- vascular interventions and fit the data with a 2D function. To estimate the XD(Fluoroscopy) we derived a curve of XD versus LII-voltage for a mid- dynamic-range average pixel gray-level. Since the MAF system during clinical fluoroscopy automatically adjusts the LII voltage until the desired gray-level value is achieved, by reading that voltage we can estimate the XD(Fluoroscopy). Using the 2D-fit function, Xo(DSA) is automatically calculated for the kVp and mA values set and XD(DSA) can be estimated using the relation above. Using the inverse LII calibration curve, the proper LII-voltage can be determined for the desired average gray-level. The algorithm was implemented and evaluated in thirty-two in-vivo DSA runs on rabbits. The proper LII voltage was selected in all cases with no failures. Using the fluoroscopic LII gain setting to determine the appropriate DSA setting can greatly improve the workflow in clinical evaluations of the MAF. NIH Grants R01-EB008425, R01-EB002873 and an equipment grant from

Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma.

PubMed

Barber, L G; Sørenmo, K U; Cronin, K L; Shofer, F S

2000-01-01

A retrospective evaluation was performed on 12 cats with nonresectable, histopathologically confirmed fibrosarcomas that were treated with doxorubicin and cyclophosphamide chemotherapy. All of the tumors were located in sites potentially used for vaccination. Six cats had a greater than 50% decrease in gross tumor burden. However, the responses were not durable, with a median response duration of 125 days. All cats developed progressive disease. When animals that received other treatments after doxorubicin-based chemotherapy were eliminated from the analysis, median survival time was significantly longer for cats that responded to chemotherapy compared with the median survival time for nonresponders (242 and 83 days, respectively). These findings may serve as a basis for further evaluating the role of chemotherapy in the treatment of vaccine-associated sarcomas.

Development of the Platysma Muscle and the Superficial Musculoaponeurotic System (Human Specimens at 8–17 Weeks of Development)

PubMed Central

De la Cuadra-Blanco, C.; Peces-Peña, M. D.; Carvallo-de Moraes, L. O.; Herrera-Lara, M. E.; Mérida-Velasco, J. R.

2013-01-01

There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8–17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region. PMID:24396304

A delayed presentation of ameloblastic fibrosarcoma in an African patient.

PubMed

Chauke, Nkhensani Yvonne; Sofianos, Chrysis; Liakos, Dimitri; Ndobe, Elias

2017-08-01

A 24-year-old womanpresented with ameloblastic fibrosarcoma arising from ameloblastic fibroma. The delayed presentation accounted for the extensive destruction of the mandible and complete occlusion of her oral cavity. This resulted in an inability to eat and maintain oral hygiene. A multidisciplinary team management approach involved nutritional optimisation, segmental mandibulectomy, reconstruction with a reconstructive plate and a free anterolateral thigh flap to line the the floor of mouth. Functional and aesthetic outcome was acceptable, and the patient is planned for secondary free fibular flap bony reconstruction. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Multicentric Fibrosarcoma in a Cat and a Review of the Literature

PubMed Central

Harasen, G. L. G.

1984-01-01

A case of multicentric fibrosarcoma in a ten month old domestic short-haired cat is presented and discussed. Tumor tissue was found to involve the right distal forepaw, right shoulder area and a popliteal lymph node. This anaplastic neoplasm was concentrated primarily in subcutaneous tissues but also extended to muscle, bone and lung. The cat was found to be positive for feline leukemia virus by the ELISA test. Based on these findings, it is likely that the lesions in this case result from an interaction between the feline leukemia virus and feline sarcoma virus. ImagesFigures 1 and 2.Figure 3.Figure 4. PMID:17422403

Feline vaccine-associated fibrosarcoma induced by aluminium compound in two cats: short communication.

PubMed

Deim, Zoltán; Palmai, Nimród; Cserni, Gábor

2008-03-01

Two cases of feline vaccine-associated fibrosarcoma (FVAF) are reported. The excised tumours were both characterised as well circumscribed, subcutaneous, firm and white with central necrosis. Histopathologically, they consisted of well-differentiated and variably sized and shaped anaplastic cells, characterised by marked nuclear and cellular pleomorphism including giant cells. The mitotic activity was low. Aluminium was demonstrated in the central necrosis and giant cells. Neoplastic cells were positive for vimentin and negative for desmin and cytokeratin. The presence of feline sarcoma virus and feline immunodeficiency virus could not be detected by PCR in either case.

Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene.

PubMed Central

Tahira, T; Hayashi, K; Ochiai, M; Tsuchida, N; Nagao, M; Sugimura, T

1986-01-01

Restriction enzyme maps were made of the region around exons 1 and 2 of activated c-Ki-ras of a fibrosarcoma (1,8-DNP2) induced in a rat by 1,8-dinitropyrene. Nucleotide sequence analysis revealed that activated c-Ki-ras shows a G----T transversion in codon 12 and consequently encodes cysteine instead of glycine in normal rat c-Ki-ras. PMID:3023884

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells.

PubMed Central

Ligueros, M.; Jeoung, D.; Tang, B.; Hochhauser, D.; Reidenberg, M. M.; Sonenberg, M.

1997-01-01

The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin D1-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and cyclin D1. Flow cytometry of MCF-7 cells at 24 h indicated that 10 microM gossypol inhibited DNA synthesis by producing a G1/S block. Western blot analysis using anti-human Rb antibodies and anti-human cyclin D1 antibodies in MCF-7 cells and high- and low-expression cyclin D1-transfected fibrosarcoma cells indicated that, after 6 h exposure, gossypol decreased the expression levels of these proteins in a dose-dependent manner. Gossypol also decreased the ratio of phosphorylated to unphosphorylated Rb protein in human mammary cancer and fibrosarcoma cell lines. Gossypol (10 microM) treated also decreased cyclin D1-associated kinase activity on histone H1 used as a substrate in MCF-7 cells. These results suggest that gossypol might suppress growth by modulating the expression of cell cycle regulatory proteins Rb and cyclin D1 and the phosphorylation of Rb protein. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:9218727

Amplification of the major satellite DNA family (FA-SAT) in a cat fibrosarcoma might be related to chromosomal instability.

PubMed

Santos, Sara; Chaves, Raquel; Adega, Filomena; Bastos, Estela; Guedes-Pinto, Henrique

2006-01-01

Most mammalian chromosomes have satellite DNA sequences located at or near the centromeres, organized in arrays of variable size and higher order structure. The implications of these specific repetitive DNA sequences and their organization for centromere function are still quite cloudy. In contrast to most mammalian species, the domestic cat seems to have the major satellite DNA family (FA-SAT) localized primarily at the telomeres and secondarily at the centromeres of the chromosomes. In the present work, we analyzed chromosome preparations from a fibrosarcoma, in comparison with nontumor cells (epithelial tissue) from the same individual, by in situ hybridization of the FA-SAT cat satellite DNA family. This repetitive sequence was found to be amplified in the cat tumor chromosomes analyzed. The amplification of these satellite DNA sequences in the cat chromosomes with variable number and appearance (marker chromosomes) is discussed and might be related to mitotic instability, which could explain the exhibition of complex patterns of chromosome aberrations detected in the fibrosarcoma analyzed.

Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

NASA Astrophysics Data System (ADS)

Ma, Zhan; Hu, Yao; Jiang, Guoying; Hou, Jun; Liu, Ruilai; Lu, Yuan; Liu, Chunfang

2012-10-01

Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

Pardaxin, a Fish Antimicrobial Peptide, Exhibits Antitumor Activity toward Murine Fibrosarcoma in Vitro and in Vivo

PubMed Central

Wu, Shu-Ping; Huang, Tsui-Chin; Lin, Ching-Chun; Hui, Cho-Fat; Lin, Cheng-Hui; Chen, Jyh-Yih

2012-01-01

The antitumor activity of pardaxin, a fish antimicrobial peptide, has not been previously examined in in vitro and in vivo systems for treating murine fibrosarcoma. In this study, the antitumor activity of synthetic pardaxin was tested using murine MN-11 tumor cells as the study model. We show that pardaxin inhibits the proliferation of MN-11 cells and reduces colony formation in a soft agar assay. Transmission electron microscopy (TEM) showed that pardaxin altered the membrane structure similar to what a lytic peptide does, and also produced apoptotic features, such as hollow mitochondria, nuclear condensation, and disrupted cell membranes. A qRT-PCR and ELISA showed that pardaxin induced apoptosis, activated caspase-7 and interleukin (IL)-7r, and downregulated caspase-9, ATF 3, SOCS3, STAT3, cathelicidin, p65, and interferon (IFN)-γ suggesting that pardaxin induces apoptosis through the death receptor/nuclear factor (NF)-κB signaling pathway after 14 days of treatment in tumor-bearing mice. An antitumor effect was observed when pardaxin (25 mg/kg; 0.5 mg/day) was used to treat mice for 14 days, which caused significant inhibition of MN-11 cell growth in mice. Overall, these results indicate that pardaxin has the potential to be a novel therapeutic agent to treat fibrosarcomas. PMID:23015777

The anabolic effects of vitamin D-binding protein-macrophage activating factor (DBP-MAF) and a novel small peptide on bone.

PubMed

Schneider, Gary B; Grecco, Kristina J; Safadi, Fayez F; Popoff, Steven N

2003-01-01

Vitamin D-binding protein-macrophage activating factor (DBP-MAF) has previously been shown to stimulate bone resorption and correct the skeletal defects associated with osteopetrosis in two nonallelic mutations in rats. This same protein and a small fragment of the protein have now been shown to demonstrate an anabolic effect on the skeleton of both newborn and young adult, intact rats. The novel peptide fragment was synthetically produced based on the human amino acid sequence at the site of glycosylation in the third domain of the native protein (DBP). The peptide tested is 14 amino acids in length and demonstrates no homologies other than to that region of DBP. Newborn rats were injected i.p. with saline, peptide (0.4 ng/g body wt.) or DBP-MAF (2 ng/g body wt.) every other day from birth to 14 days of age. On day 16 the rats were euthanized and the long bones collected for bone densitometry by pQCT. After 2 weeks of treatment with either the whole protein (DBP-MAF) or the small peptide, bone density was significantly increased in the treated animals compared to the saline controls. Young adult female rats (180 grams) were given s.c. injections of saline or peptide (0.4 ng/g body wt. or 5 ng/g body wt.) every other day for 2 weeks; 2 days after the final injections, the rats were euthanized and the femurs and tibias collected for bone densitometry. Both doses of the peptide resulted in significant increases in bone density as determined by pQCT. Young adult rats were injected locally with a single dose of the peptide (1 microg) or saline into the marrow cavity of the distal femur. One week after the single injection, the bones were collected for radiographic and histological evaluation. The saline controls showed no evidence of new bone formation, whereas the peptide-treated animals demonstrated osteoinduction in the marrow cavity and osteogenesis of surrounding cortical and metaphyseal bone. These data suggest that DBP-MAF and the synthetic peptide represent

Immunohistochemical expression of c-KIT protein in feline soft tissue fibrosarcomas.

PubMed

Smith, A J; Njaa, B L; Lamm, C G

2009-09-01

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P = .141, X(2) = 2.166), survivability (P = .241, X(2) = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P = .074, X(2) = 3.184).

Apoptosis of mouse MS-2 fibrosarcoma cells induced by photodynamic therapy with Zn (II)-phthalocyanine.

PubMed

Zhou, C; Shunji, C; Jinsheng, D; Junlin, L; Jori, G; Milanesi, C

1996-05-01

The destructive process of mouse MS-2 fibrosarcoma induced by photodynamic therapy (PDT) with liposome-administered Zn(II)-phthalocyanine (ZnPc) was studied by electron microscopy. Pronounced ultrastructural changes characteristic of apoptosis were observed for several tumour cells, including early occurrence of condensation and margination of chromatin, disappearance of nuclear pores, karyopyknosis, karyorrhexis, protuberance formation at the cell surface and cell fragmentation. The findings indicate that apoptosis was involved in the process of tumour cell death induced by ZnPc-PDT. The detailed mechanism and pathways controlling this phenomenon need to be elucidated further.

Gestational Diabetes Mellitus From Inactivation of Prolactin Receptor and MafB in Islet β-Cells.

PubMed

Banerjee, Ronadip R; Cyphert, Holly A; Walker, Emily M; Chakravarthy, Harini; Peiris, Heshan; Gu, Xueying; Liu, Yinghua; Conrad, Elizabeth; Goodrich, Lisa; Stein, Roland W; Kim, Seung K

2016-08-01

β-Cell proliferation and expansion during pregnancy are crucial for maintaining euglycemia in response to increased metabolic demands placed on the mother. Prolactin and placental lactogen signal through the prolactin receptor (PRLR) and contribute to adaptive β-cell responses in pregnancy; however, the in vivo requirement for PRLR signaling specifically in maternal β-cell adaptations remains unknown. We generated a floxed allele of Prlr, allowing conditional loss of PRLR in β-cells. In this study, we show that loss of PRLR signaling in β-cells results in gestational diabetes mellitus (GDM), reduced β-cell proliferation, and failure to expand β-cell mass during pregnancy. Targeted PRLR loss in maternal β-cells in vivo impaired expression of the transcription factor Foxm1, both G1/S and G2/M cyclins, tryptophan hydroxylase 1 (Tph1), and islet serotonin production, for which synthesis requires Tph1. This conditional system also revealed that PRLR signaling is required for the transient gestational expression of the transcription factor MafB within a subset of β-cells during pregnancy. MafB deletion in maternal β-cells also produced GDM, with inadequate β-cell expansion accompanied by failure to induce PRLR-dependent target genes regulating β-cell proliferation. These results unveil molecular roles for PRLR signaling in orchestrating the physiologic expansion of maternal β-cells during pregnancy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Radiation therapy and surgery for fibrosarcoma in 33 cats.

PubMed

Cronin, K; Page, R L; Spodnick, G; Dodge, R; Hardie, E N; Price, G S; Ruslander, D; Thrall, D E

1998-01-01

Thirty-three cats with histologically confirmed fibrosarcomas were treated with radiation therapy followed by surgery. The median (95% confidence interval) disease free interval and overall survival were 398 (261,924) and 600 (lower limit 515) days, respectively. There were 19 treatment failures; 11 cats had only local recurrence, 4 cats developed metastatic disease, 3 cats had local recurrence followed by metastasis, and 1 cat developed simultaneous local and distant disease. Twelve cats are alive and disease free. Two cats died without evidence of treatment failure. The presence of tumor cells at the margin of resected tissue after radiation was the only variable which influenced treatment success. The median (95% confidence interval) disease free interval in 5 cats with tumor cells at the margin of the resected specimen was 112 (94,150) days versus 700 (lower limit 328) days for 26 cats with negative tumor margins, p < 0.0001. We did not identify a relationship between tumor volume, number of prior tumor excisions, concomitant use of chemotherapy or various descriptors of the radiation therapy technique and disease free interval.

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.

PubMed

Hüttinger, Cornelia; Hirschberger, Johannes; Jahnke, Anika; Köstlin, Roberto; Brill, Thomas; Plank, Christian; Küchenhoff, Helmut; Krieger, Stefan; Schillinger, Ulrike

2008-06-01

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.

Huaier aqueous extract induces apoptosis of human fibrosarcoma HT1080 cells through the mitochondrial pathway

PubMed Central

CUI, YANG; MENG, HONGMEI; LIU, WEIDONG; WANG, HUAN; LIU, QINGPENG

2015-01-01

In recent years, aqueous extract of Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine, has been frequently used in China for complementary cancer therapy. However, the mechanisms underlying its anticancer effects have yet to be elucidated. The present study aimed to evaluate the ability of Huaier extract to inhibit proliferation, promote apoptosis and suppress mobility in the fibrosarcoma HT1080 cell line in vitro. The cells were treated with gradient doses of Huaier extract at concentrations of 0, 4, 8 or 16 mg/ml for 24, 48 or 72 h. The cell viability and motility were measured in vitro using MTT, invasive, migration and scratch assays. The distribution of the cell cycle and the extent of cellular apoptosis were analyzed by flow cytometry. The apoptotic pathways were detected using a mitochondrial membrane potential transition assay and western blotting. The results revealed that the cellular viability decreased significantly with increasing concentrations of Huaier extract. In addition, cell invasiveness and migration were also suppressed significantly. It was demonstrated that Huaier extract induced G2 cell-cycle arrest and cellular apoptosis in a time- and dose-dependent manner. The decreased mitochondrial membrane potential, the downregulation of B-cell lymphoma 2 and pro-caspase-3, and upregulation of Bcl-2-associated X protein, cleaved caspase-9 and caspase-3 suggested that Huaier extract induced the apoptosis of HT1080 cells through the mitochondrial pathway. The results of the present study indicate that Huaier extract is a potential complementary agent for the treatment of fibrosarcoma. PMID:25789006

Congenital Fibrosarcoma and History of Prenatal Exposure to Petroleum Derivatives

PubMed Central

Soldin, Offie P.; López-Hernández, Fernando A.; Trasande, Leonardo; Ferrís-Tortajada, Josep

2012-01-01

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame–an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy. PMID:22945410

Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and fibrosarcoma.

PubMed

Koka, V; Vericel, R; Lartigau, E; Lusinchi, A; Schwaab, G

1994-11-01

Forty-two patients were treated for sarcoma of the nasal cavity and paranasal sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III tumours. All but 10 patients had surgery for the primary tumour. A significantly increased risk of local failure was associated with the male sex (p < 0.01), grade III tumours (p < 0.02) and patients excluded from surgery (p < 0.04). The overall incidence of local and distant failure was 76 and 12 per cent respectively. Overall survival was 28 per cent at three years and 23 per cent at five years. Eight patients (20 per cent) were alive more than 10 years later. The factors significantly influencing survival were sex (p < 0.01), grade (p < 0.05) and local failure (p < 0.01).

Ameloblastic fibrosarcoma of the upper jaw: Report of a rare case with long-term follow-up

PubMed Central

Khalili, Maryam; Shakib, Pouyan Amini

2013-01-01

Ameloblastic fibrosarcoma (AFS) is a rare malignant mixed odontogenic tumor which is usually considered as the malignant counterpart of ameloblastic fibroma. Only mesenchymal component represents sarcomatous alterations and ameloblast-like epithelial nest remains bland in AFS. Here, we report a case of AFS in a 26-year-old man in the maxilla, which was regarded as an uncommon location for this tumor. After 2 years follow up, no evidence of recurrence was noted. We also emphasize on comprehensive clinical, radiographic, and histopathologic evaluation of such patients rather than immunohistochemical staining to make an accurate diagnosis. PMID:23878574

MafK/NF-E2 p18 is required for beta-globin genes activation by mediating the proximity of LCR and active beta-globin genes in MEL cell line.

PubMed

Du, Mei-Jun; Lv, Xiang; Hao, De-Long; Zhao, Guo-Wei; Wu, Xue-Song; Wu, Feng; Liu, De-Pei; Liang, Chih-Chuan

2008-01-01

Evidences indicate that locus control region (LCR) of beta-globin spatially closes to the downstream active gene promoter to mediate the transcriptional activation by looping. DNA binding proteins may play an important role in the looping formation. NF-E2 is one of the key transcription factors in beta-globin gene transcriptional activation. To shed light on whether NF-E2 is involved in this process, DS19MafKsiRNA cell pools were established by specifically knocked down the expression of MafK/NF-E2 p18, one subunit of NF-E2 heterodimer. In the above cell pools, it was observed that the occupancy efficiency of NF-E2 on beta-globin gene locus and the expression level of beta-globin genes were decreased. H3 acetylation, H3-K4 methylation and the deposition of RNA polymerase II, but not the recruitment of GATA-1, were also found reduced at the beta-globin gene cluster. Chromosome Conformation Capture (3C) assay showed that the cross-linking frequency between the main NF-E2 binding site HS2 and downstream structural genes was reduced compared to the normal cell. This result demonstrated that MafK/NF-E2 p18 recruitment was involved in the physical proximity of LCR and active beta-globin genes upon beta-globin gene transcriptional activation.

Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell

PubMed Central

hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

2013-01-01

Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-β-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 μmol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

The use of a latissimus dorsi muscle flap for scapular reconstruction in a cat following fibrosarcoma excision.

PubMed

Canapp, S O; Mann, F A; Henry, C J; Lattimer, J C

2001-01-01

A latissimus dorsi muscle flap was used to reconstruct a proximal scapular defect in a cat after excision of a fibrosarcoma that had recurred after eight surgeries, radiation therapy, and chemotherapy. To obtain appropriate surgical margins, infraspinatus and supraspinatus myectomy and scapular spinous ostectomy were performed. The latissimus dorsi muscle flap was rotated into the defect and anchored to four holes placed in the cranial border of the scapula. The cat showed no lameness at 6, 21, 42, and 147 days after surgery. The latissimus dorsi muscle flap was successful for proximal scapular reconstruction in this cat.

Biological behavior of tumors and associated retroviremia in cats inoculated with Snyder-Theilen fibrosarcoma virus and the phenomenon of tumor recurrence after primary regression.

PubMed Central

Pedersen, N C; Johnson, L; Theilen, G H

1984-01-01

The fate of tumors and associated retroviremia was studied in 111 cats infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV). Tumors appeared at the site of inoculation within 7 to 10 days. A retroviremia, due mainly to the associated feline leukemia virus helper virus (FeLV-helper), developed at the same time as tumors. Of the cats, 44 developed progressively growing tumors and therefore had to be killed, and 67 developed tumors that regressed. There was a strong correlation between the persistence of the accompanying retroviremia and the growth of the tumors. The 44 cats with progressively growing fibrosarcomas remained retroviremic until death. Conversely, 53 of the 67 cats with solitary, regressing tumors were only transiently retroviremic. Tumor regression in these cats paralleled the disappearance of retrovirus from the blood. The fate of tumors and retroviremia was not always the same, however. Twelve cats remained persistently retroviremic after all signs of gross tumors disappeared. Two other kittens became nonviremic within 20 days after inoculation, yet tumors continued to grow and even metastasize for another 3 to 5 weeks before regressing. Fibrosarcomas recurred 3 weeks to 8 months later in 8 of 12 persistently retroviremic cats with regressed tumors. Although the blood and bone marrow from these cats contained predominantly FeLV-helper, tumor cells yielded both FeSV and FeLV-helper. Of 53 animals, 3 developed recurrent fibrosarcomas 5 weeks to 8 months after all signs of tumors and retroviremia had disappeared. Cells cultured from these tumors appeared initially like normal fibroblasts and were virus nonproducers. After one to three passages in culture, however, cells became malignantly transformed and replicated both FeSV and FeLV-helper. Cultures of the bone marrow from these and other nonviremic cats with regressed tumors yielded only FeLV-helper. PMID:6319286

Oral and maxillofacial sclerosing epithelioid fibrosarcoma: report of five cases.

PubMed

Folk, Gretchen S; Williams, Stephen B; Foss, Robert B; Fanburg-Smith, Julie C

2007-09-01

Sclerosing epithelioid fibrosarcoma (SEF) has distinctive morphology and occurs mainly in deep soft tissue of adult extremities. Approximately 59 cases of SEF have been reported, with only 12 previously described in head and neck locations. Lesions involving the oral and maxillofacial region (OMFR) and intraosseous examples are rare. We present five cases of OMFRSEF. The OMF Pathology Department Registry was searched for cases coded from 1990 to the present as "SEF," "fibrosarcoma not otherwise specified" or "neoplasm of uncertain histiogenesis." Inclusion required OMFR location, an abundantly sclerotic sarcoma with epithelioid features, and lack of other phenotype by immunohistochemistry. Five cases of SEF included 3 males and 2 females. The age of the patients were: 19, 22, 35, 47 and 47 years. Tumor location included the infra-temporal fossa, buccal mucosa (recurrence extending into bone), anterior mandible (intraosseous primary, focally extending into soft tissue), and left parotid and submandibular gland (with metaplastic bone) regions. Tumor sizes ranged from 1.0 to 5.7 cm, median 3.5 cm. Histologically, the tumors were well delineated and multinodular, separated by fibrous septae. The spindled to primarily epithelioid tumor cells formed moderately cellular sheets and cords of irregularly contoured medium to large, round to oval, occasionally overlapping nuclei, indistinct nucleoli, wispy eosinophilic (retracting) cytoplasm, and distinctive cytoplasmic borders, embedded in osteoid-like stroma. Hemangiopericytoid (HPC-like) vessels were observed. Despite numerous apoptotic cells, mitoses were generally low; necrosis was present in two cases. Three tumors were graded as 2/3 and two 1/3. Immunohistochemically, the tumor cells were positive for vimentin, 1 case focally for CD34, whereas all cases were negative for S100 protein, keratins, EMA, desmin, and SMA. Wide or radical excision was performed with no adjuvant therapy. Follow-up revealed that 4 cases recurred

The radiosensitivity of a murine fibrosarcoma as measured by three cell survival assays.

PubMed Central

Rice, L.; Urano, M.; Suit, H. D.

1980-01-01

The radiation sensitivity of a weakly immunogenic spontaneous fibrosarcoma of the C3Hf/Sed mouse (designated FSa-II) was assessed by three in vivo cell survival methods: end-point dilution (TD50) assay, lung colony (LC) assay, and agar diffusion chamber (ADC) assay. The hypoxic fraction of this tumour was also determined by the ADC method. Although there was a good agreement of the cell survival data between the ADC and LC methods, the TD50 method yielded a considerably less steep cell survival curve. Beneficial aspects and limitations of each assay are discussed. In addition, the use of the ADC method for the growth of xenogeneic cell lines and a preliminary experiment with human tumour cells in non-immunosuppressed hosts suggest that this method may be a valuable adjunct for studying the growth and therapeutic responses of human tumour cells. PMID:6932931

Atypical fibrosarcomas derived from cutaneous ganglion cell-like cells in 2 domestic Djungarian hamsters (Phodopus sungorus).

PubMed

Kondo, Hirotaka; Onuma, Mamoru; Shibuya, Hisashi; Sato, Tsuneo; Abbott, Jeffrey R

2011-07-01

Androgen-dependent atypical fibromas are benign tumors derived from ganglion-cell-like cells that are particular to Djungarian hamsters (Phodopus sungorus). Masses excised from 2 hamsters were composed of pleomorphic ganglion cell-like cells supported by small to moderate amounts of collagenous matrix. Intracytoplasmic fibrils were present in silver-stained sections, and immunohistochemistry showed that the cells expressed vimentin, androgen receptor, and, in one case, estrogen receptor α. In contrast to previously reported atypical fibromas, these tumors had features of anaplasia and were locally invasive. We diagnosed the tumors as atypical fibrosarcomas and consider them an unusual malignant counterpart of atypical fibroma. Copyright 2011 by the American Association for Laboratory Animal Science

Saturn Apollo Program

NASA Image and Video Library

1967-11-01

This image depicts a Boeing worker installing an F-1 engine on the Saturn V S-IC flight stage at the Michoud Assembly Facility (MAF). The Saturn IB and Saturn V first stages were manufactured at the MAF, located 24 kilometers (approximately 15 miles) east of downtown New Orleans, Louisiana. The prime contractors, Chrysler and Boeing, jointly occupied the MAF. The basic manufacturing building boasted 43 acres under one roof. By 1964, NASA added a separate engineering and office building, vertical assembly building, and test stage building.

Islet-specific monoamine oxidase A and B expression depends on MafA transcriptional activity and is compromised in type 2 diabetes.

PubMed

Ganic, Elvira; Johansson, Jenny K; Bennet, Hedvig; Fex, Malin; Artner, Isabella

2015-12-25

Lack or dysfunction of insulin producing β cells results in the development of type 1 and type 2 diabetes mellitus, respectively. Insulin secretion is controlled by metabolic stimuli (glucose, fatty acids), but also by monoamine neurotransmitters, like dopamine, serotonin, and norepinephrine. Intracellular monoamine levels are controlled by monoamine oxidases (Mao) A and B. Here we show that MaoA and MaoB are expressed in mouse islet β cells and that inhibition of Mao activity reduces insulin secretion in response to metabolic stimuli. Moreover, analysis of MaoA and MaoB protein expression in mouse and human type 2 diabetic islets shows a significant reduction of MaoB in type 2 diabetic β cells suggesting that loss of Mao contributes to β cell dysfunction. MaoB expression was also reduced in β cells of MafA-deficient mice, a mouse model for β cell dysfunction, and biochemical studies showed that MafA directly binds to and activates MaoA and MaoB transcriptional control sequences. Taken together, our results show that MaoA and MaoB expression in pancreatic islets is required for physiological insulin secretion and lost in type 2 diabetic mouse and human β cells. These findings demonstrate that regulation of monoamine levels by Mao activity in β cells is pivotal for physiological insulin secretion and that loss of MaoB expression may contribute to the β cell dysfunction in type 2 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel p53 tumour suppressor mutations in cases of spindle cell sarcoma, pleomorphic sarcoma and fibrosarcoma in cats.

PubMed

Mayr, B; Reifinger, M; Alton, K; Schaffner, G

1998-06-01

Twenty feline neoplasms were sequenced in the region from exons 5 to 8 for the presence of tumour suppressor gene p53 mutations. In a spindle cell sarcoma of the bladder, a missense mutation (codon 164 AAG-->GAG, lysine-->glutamic acid) in exon 5 was detected. In a pleomorphic sarcoma, a 23 bp deletion involving the splicing junction between intron 5 and exon 6 was observed. In a fibrosarcoma, a 6 bp deletion of p53 covering 2 bp of exon 7 and 4 bp of intron 7, including the splicing junction, was found. The study demonstrates three new p53 mutations in different types of sarcomas in cats.

A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells

PubMed Central

Cooper, Simon E; Hodimont, Elsie; Green, Catherine M

2015-01-01

The proliferating cell nuclear antigen (PCNA) is a conserved component of DNA replication factories, and interactions with PCNA mediate the recruitment of many essential DNA replication enzymes to these sites of DNA synthesis. A complete description of the structure and composition of these factories remains elusive, and a better knowledge of them will improve our understanding of how the maintenance of genome and epigenetic stability is achieved. To fully characterize the set of proteins that interact with PCNA we developed a bimolecular fluorescence complementation (BiFC) screen for PCNA-interactors in human cells. This 2-hybrid type screen for interactors from a human cDNA library is rapid and efficient. The fluorescent read-out for protein interaction enables facile selection of interacting clones, and we combined this with next generation sequencing to identify the cDNAs encoding the interacting proteins. This method was able to reproducibly identify previously characterized PCNA-interactors but importantly also identified RNF7, Maf1 and SetD3 as PCNA-interacting proteins. We validated these interactions by co-immunoprecipitation from human cell extracts and by interaction analyses using recombinant proteins. These results show that the BiFC screen is a valuable method for the identification of protein-protein interactions in living mammalian cells. This approach has potentially wide application as it is high throughput and readily automated. We suggest that, given this interaction with PCNA, Maf1, RNF7, and SetD3 are potentially involved in DNA replication, DNA repair, or associated processes. PMID:26030842

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice.

PubMed

Khalili, Ahmad; Hassan, Zuhair Muhammad; Shahabi, Shahram; Pourfathollah, Ali Akbar; Ostad, Seyed Nasser; Noori, Shokoofe; Mahdavi, Mehdi; Haybar, Habib; Langroudi, Ladan

2013-06-01

Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.

Radical lateral body-wall resection for fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap: a prospective clinical study of the technique and results in 6 cats.

PubMed

Lidbetter, David A; Williams, Fred A; Krahwinkel, D J; Adams, William H

2002-01-01

To describe and evaluate a technique for radical resection of the lateral body wall for treatment of fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap in cats. Prospective, clinical study. Six client-owned cats with fibrosarcoma. Six cats with histologically confirmed fibrosarcoma of the lateral body wall were staged using radiography and/or computer tomography scanning. Preoperative radiotherapy was used in 3 cats. All cats had the lateral abdominal wall resected and reconstructed with polypropylene mesh. A caudal superficial epigastric flap was mobilized and rotated to close the skin deficit. The animals were evaluated after surgery for wound complications, tumor recurrence, and metastasis. Outcome was assessed by patient examination and client consultation. Minor dehiscence of the skin flaps occurred in 2 cats, and 1 other cat was successfully resuscitated from respiratory and cardiac arrest after surgery. All tissue specimens were tumor-free at the surgical margins. Follow-up times ranged from 12 to 21 months, with a mean time of 17.2 months. None of the cats had evidence of local tumor recurrence or metastasis; outcome was judged good to excellent in all cats. Radical lateral body-wall resection and reconstruction is an effective technique for achieving local tumor control with acceptable patient morbidity. Further studies are needed to assess whether the technique will result in improved tumor-free intervals and survival times. Copyright 2002 by The American College of Veterinary Surgeons

SU-D-204-05: Quantitative Comparison of a High Resolution Micro-Angiographic Fluoroscopic (MAF) Detector with a Standard Flat Panel Detector (FPD) Using the New Metric of Generalized Measured Relative Object Detectability (GM-ROD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russ, M; Ionita, C; Bednarek, D

Purpose: In endovascular image-guided neuro-interventions, visualization of fine detail is paramount. For example, the ability of the interventionist to visualize the stent struts depends heavily on the x-ray imaging detector performance. Methods: A study to examine the relative performance of the high resolution MAF-CMOS (pixel size 75µm, Nyquist frequency 6.6 cycles/mm) and a standard Flat Panel Detector (pixel size 194µm, Nyquist frequency 2.5 cycles/mm) detectors in imaging a neuro stent was done using the Generalized Measured Relative Object Detectability (GM-ROD) metric. Low quantum noise images of a deployed stent were obtained by averaging 95 frames obtained by both detectors withoutmore » changing other exposure or geometric parameters. The square of the Fourier transform of each image is taken and divided by the generalized normalized noise power spectrum to give an effective measured task-specific signal-to-noise ratio. This expression is then integrated from 0 to each of the detector’s Nyquist frequencies, and the GM-ROD value is determined by taking a ratio of the integrals for the MAF-CMOS to that of the FPD. The lower bound of integration can be varied to emphasize high frequencies in the detector comparisons. Results: The MAF-CMOS detector exhibits vastly superior performance over the FPD when integrating over all frequencies, yielding a GM-ROD value of 63.1. The lower bound of integration was stepped up in increments of 0.5 cycles/mm for higher frequency comparisons. As the lower bound increased, the GM-ROD value was augmented, reflecting the superior performance of the MAF-CMOS in the high frequency regime. Conclusion: GM-ROD is a versatile metric that can provide quantitative detector and task dependent comparisons that can be used as a basis for detector selection. Supported by NIH Grant: 2R01EB002873 and an equipment grant from Toshiba Medical Systems Corporation.« less

A New Family of Secreted Toxins in Pathogenic Neisseria Species

PubMed Central

Jamet, Anne; Jousset, Agnès B.; Euphrasie, Daniel; Mukorako, Paulette; Boucharlat, Alix; Ducousso, Alexia; Charbit, Alain; Nassif, Xavier

2015-01-01

The genus Neisseria includes both commensal and pathogenic species which are genetically closely related. However, only meningococcus and gonococcus are important human pathogens. Very few toxins are known to be secreted by pathogenic Neisseria species. Recently, toxins secreted via type V secretion system and belonging to the widespread family of contact-dependent inhibition (CDI) toxins have been described in numerous species including meningococcus. In this study, we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We demonstrated that mafB genes encode secreted polymorphic toxins and that genes immediately downstream of mafB encode a specific immunity protein (MafI). We focused on a MafB toxin found in meningococcal strain NEM8013 and characterized its EndoU ribonuclease activity. maf genes represent 2% of the genome of pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus arguing for an important biological role. Indeed, we showed that overexpression of one of the four MafB toxins of strain NEM8013 provides an advantage in competition assays, suggesting a role of maf loci in niche adaptation. PMID:25569427

Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines

PubMed Central

Bäcker, Henrik; Polgár, Livia; Soós, Pal; Lajkó, Eszter; Láng, Orsolya; Merkely, Bela; Szabó, Gabor; Dohmen, Pascal M.; Weymann, Alexander; Kőhidai, Laszlo

2017-01-01

Background Experiments on porcine heart scaffold represent significant assays in development of immunoneutral materials for cardiac surgery. Characterization of cell-cell and cell-scaffold interactions is essential to understand the homing process of cardiac cells into the scaffolds. Material/Methods In the present study, the highly sensitive and real-time impedimetric technique of xCELLigence SP was used to monitor cell adhesion, which is the key process of recellularization in heart scaffolds. Our objectives were: (i) to characterize the effect of decellularized porcine heart scaffold on cell adhesion of human cardiovascular cells potentially used in the recellularization process; and (ii) to investigate cell-extracellular matrix element interactions for building artificial multi-layer systems, applied as cellular models of recellularization experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were investigated and the effect of decellularized porcine heart scaffold (HS) and fibronectin on cell adhesion was examined. Adhesion was quantified as slope of curves. Results Heart scaffold had neutral effect on cardiomyocytes as well as on endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin (1.480±0.021) compared to control (0.745±0.029). The combination of fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407±0.634) than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly strong adhesion profiles with marked enhancer effect by fibronectin. Conclusions Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells at the cell biological level, while fibronectin has strong cell adhesion-inducer effect, as well as an enhancer effect on activity of HS. Consequently, decellularized porcine hearts could be used as scaffolds for recellularization with cardiomyocytes and endothelial cells with fibronectin acting as a regulator, leading to construction of working bioartificial

Cassava Brown Streak Virus (Potyviridae) Encodes a Putative Maf/HAM1 Pyrophosphatase Implicated in Reduction of Mutations and a P1 Proteinase That Suppresses RNA Silencing but Contains No HC-Pro ▿

PubMed Central

Mbanzibwa, Deusdedith R.; Tian, Yanping; Mukasa, Settumba B.; Valkonen, Jari P. T.

2009-01-01

The complete positive-sense single-stranded RNA genome of Cassava brown streak virus (CBSV; genus Ipomovirus; Potyviridae) was found to consist of 9,069 nucleotides and predicted to produce a polyprotein of 2,902 amino acids. It was lacking helper-component proteinase but contained a single P1 serine proteinase that strongly suppressed RNA silencing. Besides the exceptional structure of the 5′-proximal part of the genome, CBSV also contained a Maf/HAM1-like sequence (678 nucleotides, 226 amino acids) recombined between the replicase and coat protein domains in the 3′-proximal part of the genome, which is highly conserved in Potyviridae. HAM1 was flanked by consensus proteolytic cleavage sites for ipomovirus NIaPro cysteine proteinase. Homology of CBSV HAM1 with cellular Maf/HAM1 pyrophosphatases suggests that it may intercept noncanonical nucleoside triphosphates to reduce mutagenesis of viral RNA. PMID:19386713

Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

PubMed Central

Huffman, Jennifer E.; de Vries, Paul S.; Morrison, Alanna C.; Sabater-Lleal, Maria; Kacprowski, Tim; Auer, Paul L.; Brody, Jennifer A.; Chasman, Daniel I.; Chen, Ming-Huei; Guo, Xiuqing; Lin, Li-An; Marioni, Riccardo E.; Müller-Nurasyid, Martina; Yanek, Lisa R.; Pankratz, Nathan; Grove, Megan L.; de Maat, Moniek P. M.; Cushman, Mary; Wiggins, Kerri L.; Qi, Lihong; Sennblad, Bengt; Harris, Sarah E.; Polasek, Ozren; Riess, Helene; Rivadeneira, Fernando; Rose, Lynda M.; Goel, Anuj; Taylor, Kent D.; Teumer, Alexander; Uitterlinden, André G.; Vaidya, Dhananjay; Yao, Jie; Tang, Weihong; Levy, Daniel; Waldenberger, Melanie; Becker, Diane M.; Folsom, Aaron R.; Giulianini, Franco; Greinacher, Andreas; Hofman, Albert; Huang, Chiang-Ching; Kooperberg, Charles; Silveira, Angela; Starr, John M.; Strauch, Konstantin; Strawbridge, Rona J.; Wright, Alan F.; McKnight, Barbara; Franco, Oscar H.; Zakai, Neil; Mathias, Rasika A.; Psaty, Bruce M.; Ridker, Paul M.; Tofler, Geoffrey H.; Völker, Uwe; Watkins, Hugh; Fornage, Myriam; Hamsten, Anders; Deary, Ian J.; Boerwinkle, Eric; Koenig, Wolfgang; Rotter, Jerome I.; Hayward, Caroline; Dehghan, Abbas; Reiner, Alex P.; O’Donnell, Christopher J.

2015-01-01

Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways. PMID:26105150

Long-term Analysis of Lip Augmentation With Superficial Musculoaponeurotic System (SMAS) Tissue Transfer Following Biplanar Extended SMAS Rhytidectomy.

PubMed

Richardson, Matthew Allen; Rousso, Daniel Elliott; Replogle, William H

2017-01-01

To our knowledge, long-term, objective results of lip augmentation using superficial musculoaponeurotic system (SMAS) tissue transfer beyond 1 year have not been previously described. To evaluate the efficacy, longevity, and safety of lip augmentation using SMAS tissue transfer. A retrospective single-blind cohort study was designed to evaluate all patients who underwent surgical lip augmentation using SMAS following rhytidectomy between January 1, 2000, and November, 16, 2015, at a private facial plastic surgery practice in Birmingham, Alabama. Preoperative photographs of each patient served as controls and were compared with postoperative photographs at 3 months, 1 year, and 5 years after lip augmentation. A total of 104 images (from 26 individual patients) were reviewed by 12 blinded observers using a validated lip augmentation grading scale. Lip augmentation using SMAS. Median lip volumes of all patients at each postoperative interval (3 months, 1 year, and 5 years) compared with preoperative lip volumes. Secondary outcome measures included postoperative complications. A total of 423 patients were identified who underwent surgical lip augmentation using SMAS. Sixty patients with approximately 5 years or more of postoperative photographs were reviewed for complications. Twenty-six patients had 3-month, 1-year, and 5-year postoperative follow-up photographs and were included in the photographic evaluation. The mean age of these patients at the time of surgery was 54.6 years (range, 41.2-80.6 years. Fifty-nine of the 60 patients (98.3%) were female. Two of 60 patients (3.3%) with 5 years or more of postoperative follow-up developed complications requiring intervention. Both the superior lip and the inferior lip showed statistically significant increases in volume at 3 months, 1 year, and 5 years (P ≤ .004 for the superior lip after 5 years; P ≤ .001 for all other comparisons) after SMAS lip augmentation. The greatest median increase was observed in the

A case of interscapular fibrosarcoma in a dwarf rabbit (Oryctolagus cuniculus).

PubMed

Petterino, Claudio; Modesto, Paola; Strata, Daniela; Vascellari, Marta; Mutinelli, Franco; Ferrari, Angelo; Ratto, Alessandra

2009-11-01

A 1-year-old, intact, male dwarf rabbit (Oryctolagus cuniculus) was vaccinated against myxomatosis and rabbit viral hemorrhagic disease in February 1999, and a localized reaction appeared in the same anatomic site within a few days. No regression was observed after subcutaneous antibiotic treatment. The rabbit was kept under observation, and the swelling apparently disappeared in 3 months. The owner then decided to avoid any further subcutaneous drug administration. The referring veterinarian examined the animal on July 2006 for the sudden appearance of a nodular, 4.5 cm x 3.5 cm x 2.0 cm, subcutaneous mass located over the interscapular space. Fine-needle aspiration was performed, and a population of neoplastic spindle cells, rare pleomorphic multinucleated cells, and rare leukocytes were observed. The mass was surgically removed, fixed in 10% neutral buffered formalin, and routinely processed for histologic, histochemical, and immunohistochemical diagnostic investigation. The neoplastic tissue exhibited fascicles composed of malignant spindle-shaped cells with elongated to oval hyperchromatic nuclei and scant cytoplasm. Occasional multinucleated cells were also observed. The neoplastic cells were immunoreactive for vimentin but did not stain for smooth muscle actin, desmin, myoglobin, and cytokeratins (AE1/AE3). Moreover, the histochemical stain for aluminum was positive. The diagnosis was fibrosarcoma based on morphologic and immunohistochemical results. The histologic features of this neoplasm were remarkably similar to feline injection-site sarcoma.

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Meng-Yu; Nestvold, Janne, E-mail: j.m.nestvold@medisin.uio.no; Rekdal, Øystein

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cellmore » marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. - Highlights: • Spontaneously transformed rat MSCs (rTMSCs) share characteristics with normal MSCs. • rTMSCs possess a side population, enriched with tumorigenic cells. • rTMSCs model fibrosarcoma in vivo.« less

Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice

PubMed Central

Ebrahimpour, Soheil; Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Aghajanzadeh, Hamid; Behzadi, Manijeh Yousefi

2013-01-01

Background: Garlic, a medicinal plant, and Naltrexone (NTX), an opioid receptor antagonist, both have immunomodulatory and antitumor effects. Current study was designed to evaluate synergistic antitumor effects of aged garlic extract (AGE) and NTX. Materials and Methods: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into right flank of 80 BALB/c mice at age of 8 weeks. Mice were randomly categorized in four separate groups: The first group received AGE (100 mg/kg, i.p.), the second group received NTX (0.5 mg/kg, i.p.), the third group received both of them, and the fourth group received phosphate buffered saline as control group. Treatments were administered three times per week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flowcytometery. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) cytokines were measured. All statistical analyses were conducted with SPSS 16 software and P < 0.05 was considered to be statistically significant. Results: The mice who received AGE+NTX had significantly longer survival time compared with the mice treated with AGE or NTX alone. An enhanced inhibitory effect on tumor growth was seen in combination therapy group. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE+NTX and NTX groups. WEHI-164 specific cytotoxicity of splenocytes was also significantly increased at 25:1 E:T ratio in AGE+NTX treated mice. Coadministration of AGE with NTX resulted in improvement of immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. Conclusions: AGE showed synergistic effects with NTX on inhibition of tumor growth and increment of survival times. PMID:23901215

Molecular Toxicology of Chromatin: The Role of Poly(ADP-Ribose) in Gene Control.

DTIC Science & Technology

1985-02-01

04 4 0V 0 r4. $) 4 0n U) Ln 𔃺 V W 0 Ř (u %D -T -a Ai j4 W0 .. 04 04 0 04rd 412% I cb 01 41 410 41 .j A . . to 2.4 Ř -A 411 0 2 0 -r 0. 04 0A CAt e4...reported previously (1). The selection procedures used for NNSF * were compared with fibrosarcoma . Ieionmyosarcoui and synovial sarcoma cells. V...tumor incidence of human fibrosarcoma , lelomyosarcoma and synovial sarcoma cells in nude mice was identical with that of UV-transformed human

Local immunotherapy of spontaneous feline fibrosarcomas using recombinant poxviruses expressing interleukin 2 (IL2).

PubMed

Jourdier, T-M; Moste, C; Bonnet, M-C; Delisle, F; Tafani, J-P; Devauchelle, P; Tartaglia, J; Moingeon, P

2003-12-01

We tested the canarypox virus vector ALVAC and the genetically attenuated vaccinia virus vector NYVAC as vehicles for achieving local immunomodulation in domestic animals bearing spontaneous tumours. Following intratumoral administration of ALVAC-, or NYVAC-luciferase in dogs with melanoma, it was demonstrated that viral recombinants remained localized along the needle track, with no virus detectable in the periphery of the tumour. Given these distribution characteristics and their well-documented safety profile, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats, in order to prevent the recurrence of spontaneous fibrosarcomas. In the absence of immunotherapy, tumour recurrence was observed in 61% of animals within a 12-month follow-up period after treatment with surgery and iridium-based radiotherapy. In contrast, only 39 and 28% of cats receiving either NYVAC-human IL2 or ALVAC-feline IL2, respectively, exhibited tumour recurrences. Based on such results, and in the context of ongoing clinical studies conducted in humans, we discuss the utilization of ALVAC- or NYVAC-based recombinants as viable therapeutic modalities for local immunotherapy or therapeutic vaccination against cancer, both in humans and companion animals.

Pycnogenol (PYC) induces apoptosis in human fibrosarcoma (HFS) cells under metal-mediated oxidative stress.

PubMed

Park, Yeon Sun; Kim, Young Gon

2011-01-01

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pretreatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in dose dependent fashion, more apoptotic cells were induced in HFS cells with increased [8-OHdG] than in HFB cells. The results suggest that PYC selectively induced cell death in HFS cells. This further confirmed that PYC-induced apoptosis is mediated primarily through the activation of caspase-3 apoptotic marker in HFS cells but not in HFB cells. We conclude that PYC would behave as either antioxidant or prooxidant dependant upon the cellular types.

Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

PubMed

Amirkhosravi, M; Francis, J L

1995-01-01

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-11-01

Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g. A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions. We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.

Fibrosarcoma of the jaws: two cases of primary tumors with intraosseous growth.

PubMed

Angiero, Francesca; Rizzuti, Tommaso; Crippa, Rolando; Stefani, Michele

2007-01-01

Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that rarely affects the oral cavity. Two cases of primary FS of the jaws with intraosseous growth (2 men, aged 53 and 71 years) are described. Microscopically, in one case the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, with significant mitotic activity and nuclear pleomorphism; the second case was characterized by low cellularity comprising spindle-shaped cells, deposited in a variably fibrous and myxoid stroma. On immunohistochemistry, cells in both cases were strongly immunoreactive for MIB-1 and vimentin, focally positive for CD68, and negative for S-100 protein, pancytokeratin, HMB45, CD34, desmin, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). Based on clinical, histological and immunohistochemical findings, the final diagnosis was FS in the first case, myxofibrosarcoma in the second. Treatment was radical surgery with mandibular reconstruction. After two years, the first patient displayed multiple metastases and died during the third year after the initial diagnosis; the second patient was still alive and doing well five years after treatment. We discuss the differential diagnosis versus other forms of sarcoma, examining the morphological appearance that is frequently very similar, the immunohistochemical expression of MIB-1, vimentin, S-100, CD-34, CD68, EMA, as well as conventional clinicopathological features that may help to distinguish FS from other sarcomas.

Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.

PubMed

Gregory, Kalvin J; Zhao, Bing; Bielenberg, Diane R; Dridi, Sami; Wu, Jason; Jiang, Weihua; Huang, Bin; Pirie-Shepherd, Steven; Fannon, Michael

2010-10-18

Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells

PubMed Central

Bielenberg, Diane R.; Dridi, Sami; Wu, Jason; Jiang, Weihua; Huang, Bin; Pirie-Shepherd, Steven; Fannon, Michael

2010-01-01

Background Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. Methods and Findings In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. Conclusions These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation. PMID:20976141

Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

PubMed

Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

1990-11-01

Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila.

PubMed

Saito, Kuniaki; Inagaki, Sachi; Mituyama, Toutai; Kawamura, Yoshinori; Ono, Yukiteru; Sakota, Eri; Kotani, Hazuki; Asai, Kiyoshi; Siomi, Haruhiko; Siomi, Mikiko C

2009-10-29

PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi. piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster, traffic jam (tj), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini, a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.

A novel branched TAT(47-57) peptide for selective Ni(2+) introduction into the human fibrosarcoma cell nucleus.

PubMed

Szyrwiel, Łukasz; Shimura, Mari; Shirataki, Junko; Matsuyama, Satoshi; Matsunaga, Akihiro; Setner, Bartosz; Szczukowski, Łukasz; Szewczuk, Zbigniew; Yamauchi, Kazuto; Malinka, Wiesław; Chavatte, Laurent; Łobinski, Ryszard

2015-07-01

A TAT47-57 peptide was modified on the N-terminus by elongation with a 2,3-diaminopropionic acid residue and then by coupling of two histidine residues on its N-atoms. This branched peptide could bind to Ni under physiological conditions as a 1 : 1 complex. We demonstrated that the complex was quantitatively taken up by human fibrosarcoma cells, in contrast to Ni(2+) ions. Ni localization (especially at the nuclei) was confirmed by imaging using both scanning X-ray fluorescence microscopy and Newport Green fluorescence. A competitive assay with Newport Green showed that the latter displaced the peptide ligand from the Ni-complex. Ni(2+) delivered as a complex with the designed peptide induced substantially more DNA damage than when introduced as a free ion. The availability of such a construct opens up the way to investigate the importance of the nucleus as a target for the cytotoxicity, genotoxicity or carcinogenicity of Ni(2+).

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Adult Fibrosarcoma; Alveolar Soft Part Sarcoma; Angiomatoid Fibrous Histiocytoma; Atypical Fibroxanthoma; Clear Cell Sarcoma of Soft Tissue; Epithelioid Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Osteosarcoma; Fibrohistiocytic Neoplasm; Glomus Tumor of the Skin; Inflammatory Myofibroblastic Tumor; Intimal Sarcoma; Leiomyosarcoma; Liposarcoma; Low Grade Fibromyxoid Sarcoma; Low Grade Myofibroblastic Sarcoma; Malignant Cutaneous Granular Cell Tumor; Malignant Peripheral Nerve Sheath Tumor; Malignant Triton Tumor; Mesenchymal Chondrosarcoma; Myxofibrosarcoma; Myxoid Chondrosarcoma; Myxoinflammatory Fibroblastic Sarcoma; Nerve Sheath Neoplasm; PEComa; Pericytic Neoplasm; Plexiform Fibrohistiocytic Tumor; Sclerosing Epithelioid Fibrosarcoma; Stage IB Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Synovial Sarcoma; Undifferentiated (Embryonal) Sarcoma; Undifferentiated High Grade Pleomorphic Sarcoma of Bone

Junctional adhesion molecule-C promotes metastatic potential of HT1080 human fibrosarcoma.

PubMed

Fuse, Chiaki; Ishida, Yuuki; Hikita, Tomoya; Asai, Tomohiro; Oku, Naoto

2007-03-16

The junctional adhesion molecule (JAM) family is a key molecule in a process called transendothelial migration or diapedesis. Here, we report implications of JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19 kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent metastatic properties. Especially in murine K-1735 melanoma cell lines, the highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080 fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells showed a significant increase in the adhesion to various extracellular substrates and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using small interfering RNA resulted in the suppression of both the adhesion and the invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo experimental metastatic model. The results showed that the overexpression of hJAM-C in HT1080 cells significantly decreased the life spans of the tumorbearing mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight gain of the lungs with metastatic colonies. We conclude that the expression of JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to extracellular matrices and the subsequent invasion.

Transcriptional response of peripheral lymphocytes to early fibrosarcoma: a model system for cancer detection based on hybridization signatures.

PubMed

Marques, Márcia M C; Junta, Cristina M; Zárate-Blades, Carlos R; Sakamoto-Hojo, Elza Tiemi; Donadi, Eduardo A; Passos, Geraldo A S

2009-07-01

Since circulating leukocytes, mainly B and T cells, continuously maintain vigilant and comprehensive immune surveillance, these cells could be used as reporters for signs of infection or other pathologies, including cancer. Activated lymphocyte clones trigger a sensitive transcriptional response, which could be identified by gene expression profiling. To assess this hypothesis, we conducted microarray analysis of the gene expression profile of lymphocytes isolated from immunocompetent BALB/c mice subcutaneously injected with different numbers of tumorigenic B61 fibrosarcoma cells. Flow cytometry demonstrated that the number of circulating T (CD3(+)CD4(+) or CD3(+)CD8(+)) or B (CD19(+)) cells did not change. However, the lymphocytes isolated from tumor cell-injected animals expressed a unique transcriptional profile that was identifiable before the development of a palpable tumor mass. This finding demonstrates that the transcriptional response appears before alterations in the main lymphocyte subsets and that the gene expression profile of peripheral lymphocytes can serve as a sensitive and accurate method for the early detection of cancer.

Pseudotumors after primary abdominal lipectomy as a new sequela in patients with abdominal apron.

PubMed

Dragu, Adrian; Bach, Alexander D; Polykandriotis, Elias; Kneser, Ulrich; Horch, Raymund E

2009-11-01

Malnutrition and overweight is a common problem in modern societies. Primary abdominal lipectomy is a standard surgical tool in patients with these problems. However, unknown secondary problems result from recent advances in obesity surgery. Plication of the anterior musculoaponeurotic wall is a widely and commonly used operative technique during abdominoplasty. Many different plication techniques have been published. So far no common standard and long-term effectiveness is proven. In addition, there is no sufficient literature dealing with the postoperative risks of plication of the musculoaponeurotic wall. Four patients with development of pseudotumors were reviewed. All four patients received 12 months in advance a primary abdominal lipectomy including a vertical plication of the musculoaponeurotic wall. All four patients were females with mean age of 61 years and mean body mass index (BMI) of 37 kg/m(2). All four patients had developed a pseudotumor of the abdomen as a long-term complication more than 12 months after primary abdominal lipectomy including a vertical plication of the anterior rectus sheath. One should be aware of the potential long-term risk of secondary postoperative hematoma formation, with or without partial necrosis of the anterior rectus sheath after vertical plication of the anterior musculoaponeurotic wall. Viewed clinically and radiologically, such sequelas may appear as pseudotumor like masses and require immediate revision.

A 5-year study of the transmalar subperiosteal midface lift with minimal skin and superficial musculoaponeurotic system dissection: a durable, natural-appearing lift with less surgery and recovery time.

PubMed

Finger, E R

2001-04-15

The transmalar subperiosteal midface lift is a simple, direct-approach procedure to be performed with a meloplasty. The entry into the midface is at the site of maximum suture tension, which allows for more elevation. The skin is elevated enough to expose the entry site, which is on the zygoma just cephalad to the origins of the zygomaticus muscles. Through a small hole at that site, a periosteal elevator is used for the midface dissection. This is a blind dissection, and the technique is described. The advantages of the technique are that there is (1) no lower-lid incision or risk of an ectropion, (2) a resultant tightening and elevation of the lower lid, (3) more elevation and durability because the zygomaticus muscle origins are elevated with the periosteum and are sutured to the very substantial deep temporal fascia, (4) a simple and fast procedure, and (5) no telltale sign of a face lift. Both the superficial musculoaponeurotic system (SMAS) and the skin are substantially elevated with the transmalar subperiosteal midface lift to the extent that they should be only minimally dissected. In the author's opinion, the extended dissection of the skin and/or the SMAS does not increase the amount of tissue lift and probably reduces it in most cases, considering that the goal is a natural look and not one that appears pulled or stretched. The skin is elevated only for exposure, and the SMAS is elevated only enough to create a preauricular SMAS-platysma flap to tighten the neck. With two fewer layers of dissection, there is significantly less postoperative swelling and recovery time. The article presents the technique, the results on 272 patients over a period of 5 years, and a discussion. No patients described have had secondary procedures such as lasers, so the transmalar subperiosteal midface lift can be evaluated on its own merit.

A remarkable adsorbent for removal of contaminants of emerging concern from water: Porous carbon derived from metal azolate framework-6.

PubMed

Bhadra, Biswa Nath; Jhung, Sung Hwa

2017-10-15

A series of metal-azolate frameworks or MAFs-MAF-4, -5, and -6-were synthesized and pyrolyzed to prepare porous carbons derived from MAFs (CDM-4, -5, -6, respectively). Not only the obtained carbons but also MAFs were characterized and applied for the adsorption of organic contaminants of emerging concern (CECs, including pharmaceuticals and personal care products) such as salicylic acid, clofibric acid, diclofenac sodium, bisphenol-A, and oxybenzone (OXB) from water. CDM-6 was found to be the most remarkable adsorbent among the tested ones (including activated carbon) for all the adsorbates. OXB was taken as a representative adsorbate for detailed adsorption studies as well as understanding the adsorption mechanism. H-bonding (H-acceptor: CDM; H-donor: CECs) was suggested as the principal mechanism for the adsorption of tested adsorbates. Finally, CDMs, especially CDM-6, were suggested as highly efficient and easily recyclable adsorbents for water purification. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

PubMed Central

Liu, C; Adamson, E; Mercola, D

1996-01-01

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hong-Ju; He, Wen-Qi; Chen, Ling

Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however,more » were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.« less

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

NASA used barges for transporting full-sized stages for the Saturn I, Saturn IB, and Saturn V vehicles between the Marshall Space Flight Center (MSFC), the manufacturing plant at the Michoud Assembly Facility (MAF), the Mississippi Test Facility for testing, and the Kennedy Space Center. The barges traveled from the MSFC dock to the MAF, a total of 1,086.7 miles up the Tennessee River and down the Mississippi River. The barges also transported the assembled stages of the Saturn vehicle from the MAF to the Kennedy Space Center, a total of 932.4 miles along the Gulf of Mexico and up along the Atlantic Ocean, for the final assembly and the launch. This photograph shows the barge Orion at the MSFC dock.

Regulation of adhesion and growth of fibrosarcoma cells by NF-kappa B RelA involves transforming growth factor beta.

PubMed Central

Perez, J R; Higgins-Sochaski, K A; Maltese, J Y; Narayanan, R

1994-01-01

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion. Images PMID:8035811

The glycosylation and characterization of the candidate Gc macrophage activating factor.

PubMed

Ravnsborg, Tina; Olsen, Dorthe T; Thysen, Anna Hammerich; Christiansen, Maja; Houen, Gunnar; Højrup, Peter

2010-04-01

The vitamin D binding protein, Gc globulin, has in recent years received some attention for its role as precursor for the extremely potent macrophage activating factor (GcMAF). An O-linked trisaccharide has been allocated to the threonine residue at position 420 in two of the three most common isoforms of Gc globulin (Gc1s and Gc1f). A substitution for a lysine residue at position 420 in Gc2 prevents this isoform from being glycosylated at that position. It has been suggested that Gc globulin subjected sequentially to sialidase and galactosidase treatment generates GcMAF in the form of Gc globulin with only a single GalNAc attached to T420. In this study we confirm the location of a linear trisaccharide on T420. Furthermore, we provide the first structural evidence of the generation of the proposed GcMAF by use of glycosidase treatment and mass spectrometry. Additionally the generated GcMAF candidate was tested for its effect on cytokine release from macrophages in human whole blood. Copyright 2010 Elsevier B.V. All rights reserved.

LC3-mediated fibronectin mRNA translation induces fibrosarcoma growth by increasing connective tissue growth factor

PubMed Central

Ying, Lihua; Lau, Agatha; Alvira, Cristina M.; West, Robert; Cann, Gordon M.; Zhou, Bin; Kinnear, Caroline; Jan, Eric; Sarnow, Peter; Van de Rijn, Matt; Rabinovitch, Marlene

2009-01-01

Summary Previously, we related fibronectin (Fn1) mRNA translation to an interaction between an AU-rich element in the Fn1 3′ UTR and light chain 3 (LC3) of microtubule-associated proteins 1A and 1B. Since human fibrosarcoma (HT1080) cells produce little fibronectin and LC3, we used these cells to investigate how LC3-mediated Fn1 mRNA translation might alter tumor growth. Transfection of HT1080 cells with LC3 enhanced fibronectin mRNA translation. Using polysome analysis and RNA-binding assays, we show that elevated levels of translation depend on an interaction between a triple arginine motif in LC3 and the AU-rich element in Fn1 mRNA. Wild-type but not mutant LC3 accelerated HT1080 cell growth in culture and when implanted in SCID mice. Comparison of WT LC3 with vector-transfected HT1080 cells revealed increased fibronectin-dependent proliferation, adhesion and invasion. Microarray analysis of genes differentially expressed in WT and vector-transfected control cells indicated enhanced expression of connective tissue growth factor (CTGF). Using siRNA, we show that enhanced expression of CTGF is fibronectin dependent and that LC3-mediated adhesion, invasion and proliferation are CTGF dependent. Expression profiling of soft tissue tumors revealed increased expression of both LC3 and CTGF in some locally invasive tumor types. PMID:19366727

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

NASA used barges for transporting full-sized stages for the Saturn I, Saturn IB, and Saturn V vehicles between the Marshall Space Flight Center (MSFC), the manufacturing plant at the Michoud Assembly Facility (MAF), the Mississippi Test Facility for testing, and the Kennedy Space Center. The barges traveled from the MSFC dock to the MAF, a total of 1,086.7 miles up the Tennessee River and down the Mississippi River. The barges also transported the assembled stages of the Saturn vehicle from the MAF to the Kennedy Space Center, a total of 932.4 miles along the Gulf of Mexico and up along the Atlantic Ocean, for the final assembly and the launch. Pictured is the barge Palaemon carrying Saturn IV S-IB flight stage enroute to MSFC.

β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development

PubMed Central

Abdellatif, Ahmed M.; Oishi, Hisashi; Itagaki, Takahiro; Jung, Yunshin; Shawki, Hossam H.; Okita, Yukari; Hasegawa, Yoshikazu; Suzuki, Hiroyuki; El-Morsy, Salah E.; El-Sayed, Mesbah A.; Shoaib, Mahmoud B.; Sugiyama, Fumihiro; Takahashi, Satoru

2016-01-01

The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas. PMID:26901059

Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2.

PubMed

Quintin-Colonna, F; Devauchelle, P; Fradelizi, D; Mourot, B; Faure, T; Kourilsky, P; Roth, C; Mehtali, M

1996-12-01

The production of human interleukin-2 (hIL-2) local to the tumor site by engineered histoincompatible cells has been shown in various murine models to promote a strong immune response leading to tumor growth inhibition or rejection. To assess whether this strategy would be similarly applicable for treatment of primary neoplastic cells, two naturally occurring tumors were used as preclinical models; the highly metastatic melanoma of the dog and the low metastatic fibrosarcoma of the cat. We demonstrate that both cats and dogs when treated by tumor surgery, radiotherapy and repeated local injections of xenogeneic Vero cells secreting high levels of hIL-2 relapse less frequently and survive longer than control animals treated by surgery and radiotherapy alone. Local secretion of hIL-2 by the xenogeneic cells is shown to be necessary for the induction of an optimal antitumor effect. Moreover, the safety of the procedure was demonstrated in both animal models and through extensive toxicological analysis performed in rats. These results confirm for the first time to our knowledge the safety and therapeutic potential of a gene transfer strategy in animals with spontaneous metastatic and nonmetastatic tumors.

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells.

PubMed

Pongkittiphan, Veerachai; Chavasiri, Warinthorn; Supabphol, Roongtawan

2015-01-01

Berberine (B1), isolated from stems of Coscinium fenestratum (Goetgh.) Colebr, was used as a principle structure to synthesize three phenolic derivatives: berberrubine (B2) with a single phenolic group, berberrubine chloride (B3) as a chloride counter ion derivative, and 2,3,9,10-tetra-hydroxyberberine chloride (B4) with four phenolic groups, to investigate their direct and indirect antioxidant activities. For DPPH assay, compounds B4, B3, and B2 showed good direct antioxidant activity (IC50 values=10.7±1.76, 55.2±2.24, and 87.4±6.65 μM, respectively) whereas the IC50 value of berberine was higher than 500 μM. Moreover, compound B4 exhibited a better DPPH scavenging activity than BHT as a standard antioxidant (IC50=72.7±7.22 μM) due to the ortho position of hydroxyl groups and its capacity to undergo intramolecular hydrogen bonding. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT reagent, the sequence of IC50 value at 7-day treatment stated that B1

DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells.

PubMed

Yu, Seon-Mi; Kim, Song-Ja

2015-10-01

The cytosine analogue 5'-azacytidine (5'-aza) induces DNA hypomethylation by inhibiting DNA methyltransferase. In clinical trials, 5'-aza is widely used in epigenetic anticancer treatments. Accumulated evidence shows that cyclooxygenase-2 (COX-2) is overexpressed in various cancers, indicating that it may play a critical role in carcinogenesis. However, few studies have been performed to explore the molecular mechanism underlying the increased COX-2 expression. Therefore, we tested the hypothesis that 5'-aza regulates COX-2 expression and prostaglandin E2 (PGE2) production. The human fibrosarcoma cell line HT1080, was treated with various concentrations of 5'-aza for different time periods. Protein expressions of COX-2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), pAkt, Akt, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (pERK) were determined using western blot analysis, and COX-2 mRNA expression was determined using RT-PCR. PGE2 production was evaluated using the PGE2 assay kit. The localization and expression of COX-2 were determined using immunofluorescence staining. Treatment with 5'-aza induces protein and mRNA expression of COX-2. We also observed that 5'-aza-induced COX-2 expression and PGE2 production were inhibited by S-adenosylmethionine (SAM), a methyl donor. Treatment with 5'-aza phosphorylates PI3-kinase/Akt and ERK-1/2; inhibition of these pathways by LY294002, an inhibitor of PI3-kinase/Akt, or PD98059, an inhibitor of ERK-1/2, respectively, prevents 5'-aza-induced COX-2 expression and PGE2 production. Overall, these observations indicate that the hypomethylating agent 5'-aza modulates COX-2 expression via the PI3-kinase/Akt and ERK-1/2 pathways in human HT1080 fibrosarcoma cells.

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

PubMed

Jahnke, A; Hirschberger, J; Fischer, C; Brill, T; Köstlin, R; Plank, C; Küchenhoff, H; Krieger, S; Kamenica, K; Schillinger, U

2007-12-01

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato] gallium complexes on breast carcinoma and fibrosarcoma cells.

PubMed

Mohsen, Ahmed; Saby, Charles; Collery, Philippe; Sabry, Gilane Mohamed; Hassan, Rasha Elsherif; Badawi, Abdelfattah; Jeannesson, Pierre; Desmaële, Didier; Morjani, Hamid

2016-10-01

Two water soluble gallium complexes described as [Ga(III)LCl], where L is the deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry, and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid derivative (GS2) has been found to be a promising anticancer drug candidate. This compound was found to be more cytotoxic against human breast carcinoma MDA-MB231 and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3. GS2 was able to induce apoptosis through downregulation of AKT phosphorylation, G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA-MB231 cells. This suggests that the mechanism of action of GS2 would not be mediated by the drug-induced oxidative stress but probably by directly and indirectly inhibiting the AKT cell-signaling pathway.

Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line.

PubMed Central

Mukaida, N; Gussella, G L; Kasahara, T; Ko, Y; Zachariae, C O; Kawai, T; Matsushima, K

1992-01-01

In order to analyse the effects of glucocorticoids on interleukin-8 (IL-8) production more precisely, we examined the effects of dexamethasone on IL-8 production at the molecular level in a human fibrosarcoma cell line, 8387, which IL-1 induces to express IL-8 messenger RNA (mRNA) and to secrete IL-8. Over a wide dose range, dexamethasone inhibited IL-8 production induced by IL-1 alpha stimulation. Northern blotting analysis showed that dexamethasone also inhibited the IL-8 mRNA accumulation in a similar dose-related manner. Nuclear run-off assay revealed that dexamethasone decreased the transcription of the IL-8 gene and the degree of inhibition of transcription correlated well with the inhibition of IL-8 production, suggesting that the action of glucocorticoids is mainly at the transcriptional level. Furthermore, transfection with chloramphenicol acetyl transferase (CAT) expression vectors inserted with the 5'-deleted IL-8 gene demonstrated that the 5'-flanking region which contains the glucocorticoid response element (GRE) was mainly involved in the dexamethasone-induced repression of the IL-8 gene. These data suggest that the inhibition of the IL-8 gene transcription by glucocorticoids occurs through the interaction of the glucocorticoid receptor complex with GRE in the 5'-flanking region of the IL-8 gene. Images Figure 1 Figure 2 Figure 3 PMID:1592440

High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range β-Globin Gene Regulation

PubMed Central

Stees, Jared R.; Hossain, Mir A.; Sunose, Tomoki; Kudo, Yasushi; Pardo, Carolina E.; Nabilsi, Nancy H.; Darst, Russell P.; Poudyal, Rosha; Igarashi, Kazuhiko; Kladde, Michael P.

2015-01-01

Enhancers and promoters assemble protein complexes that ultimately regulate the recruitment and activity of RNA polymerases. Previous work has shown that at least some enhancers form stable protein complexes, leading to the formation of enhanceosomes. We analyzed protein-DNA interactions in the murine β-globin gene locus using the methyltransferase accessibility protocol for individual templates (MAPit). The data show that a tandem Maf recognition element (MARE) in locus control region (LCR) hypersensitive site 2 (HS2) reveals a remarkably high degree of occupancy during differentiation of mouse erythroleukemia cells. Most of the other transcription factor binding sites in LCR HS2 or in the adult β-globin gene promoter regions exhibit low fractional occupancy, suggesting highly dynamic protein-DNA interactions. Targeting of an artificial zinc finger DNA-binding domain (ZF-DBD) to the HS2 tandem MARE caused a reduction in the association of MARE-binding proteins and transcription complexes at LCR HS2 and the adult βmajor-globin gene promoter but did not affect expression of the βminor-globin gene. The data demonstrate that a stable MARE-associated footprint in LCR HS2 is important for the recruitment of transcription complexes to the adult βmajor-globin gene promoter during erythroid cell differentiation. PMID:26503787

Lens-Specific Gene Recruitment of ζ-Crystallin through Pax6, Nrl-Maf, and Brain Suppressor Sites

PubMed Central

Sharon-Friling, Ronit; Richardson, Jill; Sperbeck, Sally; Lee, Douglas; Rauchman, Michael; Maas, Richard; Swaroop, Anand; Wistow, Graeme

1998-01-01

ζ-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an αCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates ζ-crystallin promoter activity in lens cells. A truncated ζ promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between −498 and −385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens. PMID:9528779

The effect of radiation therapy combined with natural killer cells against spontaneous murine fibrosarcoma.

PubMed

Nakagawa, K; Yoshida, F; Omori, N; Tsunoda, T; Nose, T

1990-01-01

The effect of radiation therapy combined with lymphoid cells against spontaneous murine fibrosarcoma (FSa-II) was investigated both in vivo and in vitro. In the in vivo experiment, syngeneic C3H mice were divided into 3 groups. Animals in the first group were injected with 1 x 10(5) tumor cells into the right hind leg. Animals in the second and third groups were injected with 1 x 10(5) tumor cells mixed with 1 x 10(7) normal lymphoid cells (NLC) or effector lymphoid cells (ELC), respectively. ELC were obtained from spleen and lymph nodes of FSa-II-bearing mice and incubated in vitro for 40 hr to eliminate suppressor T cell function. NLC were obtained from normal mice and incubated in the same way. Irradiation was given using 137Cs unit 3 days after cell inoculation. 12 out of 14 mice (85.7%) inoculated with tumor cells mixed with NLC did not show any tumor growth at 60 Gy local irradiation. 12 out of 21 mice (57.1%) inoculated with tumor cells alone and 6 out of 10 (60%) with tumor cells mixed with ELC rejected tumors at the same radiation dose. This synergistic effect with NLC was not observed when NLC was inoculated after irradiation, indicating that lymphoid cells should be in contact with tumor cells before irradiation. In the 51Cr release assay, lymphoid cells obtained from whole body irradiated (WBI) mice showed 17.8% lysis without irradiation and 28.8% lysis at 5 Gy irradiation. Untreated NLC showed almost no cytotoxic effect at the same radiation dose. This synergistic effect disappeared when WBI lymphoid cells were treated with anti asialo GM1 and complement.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative comparison using Generalized Relative Object Detectability (G-ROD) metrics of an amorphous selenium detector with high resolution Microangiographic Fluoroscopes (MAF) and standard flat panel detectors (FPD).

PubMed

Russ, M; Shankar, A; Jain, A; Setlur Nagesh, S V; Ionita, C N; Scott, C; Karim, K S; Bednarek, D R; Rudin, S

2016-02-27

A novel amorphous selenium (a-Se) direct detector with CMOS readout has been designed, and relative detector performance investigated. The detector features include a 25 μ m pixel pitch, and 1000 μ m thick a-Se layer operating at 10V/ μ m bias field. A simulated detector DQE was determined, and used in comparative calculations of the Relative Object Detectability (ROD) family of prewhitening matched-filter (PWMF) observer and non-prewhitening matched filter (NPWMF) observer model metrics to gauge a-Se detector performance against existing high resolution micro-angiographic fluoroscopic (MAF) detectors and a standard flat panel detector (FPD). The PWMF-ROD or ROD metric compares two x-ray imaging detectors in their relative abilities in imaging a given object by taking the integral over spatial frequencies of the Fourier transform of the detector DQE weighted by an object function, divided by the comparable integral for a different detector. The generalized-ROD (G-ROD) metric incorporates clinically relevant parameters (focal-spot size, magnification, and scatter) to show the degradation in imaging performance for detectors that are part of an imaging chain. Preliminary ROD calculations using simulated spheres as the object predicted superior imaging performance by the a-Se detector as compared to existing detectors. New PWMF-G-ROD and NPWMF-G-ROD results still indicate better performance by the a-Se detector in an imaging chain over all sphere sizes for various focal spot sizes and magnifications, although a-Se performance advantages were degraded by focal spot blurring. Nevertheless, the a-Se technology has great potential to provide breakthrough abilities such as visualization of fine details including of neuro-vascular perforator vessels and of small vascular devices.

Design considerations for a new, high resolution Micro-Angiographic Fluoroscope based on a CMOS sensor (MAF-CMOS).

PubMed

Loughran, Brendan; Swetadri Vasan, S N; Singh, Vivek; Ionita, Ciprian N; Jain, Amit; Bednarek, Daniel R; Titus, Albert; Rudin, Stephen

2013-03-06

The detectors that are used for endovascular image-guided interventions (EIGI), particularly for neurovascular interventions, do not provide clinicians with adequate visualization to ensure the best possible treatment outcomes. Developing an improved x-ray imaging detector requires the determination of estimated clinical x-ray entrance exposures to the detector. The range of exposures to the detector in clinical studies was found for the three modes of operation: fluoroscopic mode, high frame-rate digital angiographic mode (HD fluoroscopic mode), and DSA mode. Using these estimated detector exposure ranges and available CMOS detector technical specifications, design requirements were developed to pursue a quantum limited, high resolution, dynamic x-ray detector based on a CMOS sensor with 50 μm pixel size. For the proposed MAF-CMOS, the estimated charge collected within the full exposure range was found to be within the estimated full well capacity of the pixels. Expected instrumentation noise for the proposed detector was estimated to be 50-1,300 electrons. Adding a gain stage such as a light image intensifier would minimize the effect of the estimated instrumentation noise on total image noise but may not be necessary to ensure quantum limited detector operation at low exposure levels. A recursive temporal filter may decrease the effective total noise by 2 to 3 times, allowing for the improved signal to noise ratios at the lowest estimated exposures despite consequent loss in temporal resolution. This work can serve as a guide for further development of dynamic x-ray imaging prototypes or improvements for existing dynamic x-ray imaging systems.

The effects of different irrigation protocols on removing calcium hydroxide from the root canals.

PubMed

Üstün, Y; Aslan, T; Sagsen, B; Dincer, A N

2016-01-01

The aim of this study was to evaluate the efficiencies of different irrigation protocols and solutions in the removal of calcium hydroxide (Ca[OH]2). Sixty-eight maxillary incisors were used. Root canals were prepared and filled with Ca(OH)2. Two control (n = 4) and six experimental groups (n = 10) were adjusted: Group 1:1% peracetic acid (PAA) + master apical file (MAF); Group 2: 17% ethylenediaminetetraacetic acid (EDTA) + MAF; Group 3: 9% 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) + MAF; Group 4: 1% PAA + ultrasonic activation (UA); Group 5: 17% EDTA + UA; Group 6: 9% HEBP + UA. The cleanliness of root canal thirds were evaluated with scanning electron microscopy. Statistical analysis were performed (α = 0.05). At coronal thirds; PAA + UA was superior to EDTA + MAF, HEBP + MAF; and PAA + MAF was superior to EDTA + MAF, HEBP + MAF (P < 0.05). At middle thirds; PAA + MAF and PAA + UA were superior to EDTA + MAF and EDTA + UA; and, PAA + UA was superior to HEBP + MAF (P < 0.05). There were no significant differences among the rest of the experimental groups (P > 0.05). Complete removal of Ca(OH)2could not be achieved by none of the irrigants at all root thirds.

Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

PubMed Central

Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

2009-01-01

Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

Quantitative comparison using generalized relative object detectability (G-ROD) metrics of an amorphous selenium detector with high resolution microangiographic fluoroscopes (MAF) and standard flat panel detectors (FPD)

NASA Astrophysics Data System (ADS)

Russ, M.; Shankar, A.; Jain, A.; Setlur Nagesh, S. V.; Ionita, C. N.; Scott, C.; Karim, K. S.; Bednarek, D. R.; Rudin, S.

2016-03-01

A novel amorphous selenium (a-Se) direct detector with CMOS readout has been designed, and relative detector performance investigated. The detector features include a 25μm pixel pitch, and 1000μm thick a-Se layer operating at 10V/μm bias field. A simulated detector DQE was determined, and used in comparative calculations of the Relative Object Detectability (ROD) family of prewhitening matched-filter (PWMF) observer and non-pre-whitening matched filter (NPWMF) observer model metrics to gauge a-Se detector performance against existing high resolution micro-angiographic fluoroscopic (MAF) detectors and a standard flat panel detector (FPD). The PWMF-ROD or ROD metric compares two x-ray imaging detectors in their relative abilities in imaging a given object by taking the integral over spatial frequencies of the Fourier transform of the detector DQE weighted by an object function, divided by the comparable integral for a different detector. The generalized-ROD (G-ROD) metric incorporates clinically relevant parameters (focal- spot size, magnification, and scatter) to show the degradation in imaging performance for detectors that are part of an imaging chain. Preliminary ROD calculations using simulated spheres as the object predicted superior imaging performance by the a-Se detector as compared to existing detectors. New PWMF-G-ROD and NPWMF-G-ROD results still indicate better performance by the a-Se detector in an imaging chain over all sphere sizes for various focal spot sizes and magnifications, although a-Se performance advantages were degraded by focal spot blurring. Nevertheless, the a-Se technology has great potential to provide break- through abilities such as visualization of fine details including of neuro-vascular perforator vessels and of small vascular devices.

Quantitative comparison using Generalized Relative Object Detectability (G-ROD) metrics of an amorphous selenium detector with high resolution Microangiographic Fluoroscopes (MAF) and standard flat panel detectors (FPD)

PubMed Central

Russ, M.; Shankar, A.; Jain, A.; Setlur Nagesh, S. V.; Ionita, C. N.; Scott, C.; Karim, K. S.; Bednarek, D. R.; Rudin, S.

2017-01-01

A novel amorphous selenium (a-Se) direct detector with CMOS readout has been designed, and relative detector performance investigated. The detector features include a 25μm pixel pitch, and 1000μm thick a-Se layer operating at 10V/μm bias field. A simulated detector DQE was determined, and used in comparative calculations of the Relative Object Detectability (ROD) family of prewhitening matched-filter (PWMF) observer and non-prewhitening matched filter (NPWMF) observer model metrics to gauge a-Se detector performance against existing high resolution micro-angiographic fluoroscopic (MAF) detectors and a standard flat panel detector (FPD). The PWMF-ROD or ROD metric compares two x-ray imaging detectors in their relative abilities in imaging a given object by taking the integral over spatial frequencies of the Fourier transform of the detector DQE weighted by an object function, divided by the comparable integral for a different detector. The generalized-ROD (G-ROD) metric incorporates clinically relevant parameters (focal-spot size, magnification, and scatter) to show the degradation in imaging performance for detectors that are part of an imaging chain. Preliminary ROD calculations using simulated spheres as the object predicted superior imaging performance by the a-Se detector as compared to existing detectors. New PWMF-G-ROD and NPWMF-G-ROD results still indicate better performance by the a-Se detector in an imaging chain over all sphere sizes for various focal spot sizes and magnifications, although a-Se performance advantages were degraded by focal spot blurring. Nevertheless, the a-Se technology has great potential to provide breakthrough abilities such as visualization of fine details including of neuro-vascular perforator vessels and of small vascular devices. PMID:28615795

Emergence of novel and dominant acquired EGFR solvent-front mutations at Gly796 (G796S/R) together with C797S/R and L792F/H mutations in one EGFR (L858R/T790M) NSCLC patient who progressed on osimertinib.

PubMed

Ou, Sai-Hong Ignatius; Cui, Jean; Schrock, Alexa B; Goldberg, Michael E; Zhu, Viola W; Albacker, Lee; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M

2017-06-01

Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib. The patient was initiated on osimertinib with disease shrinkage after 2 months, but tumor regrowth was observed after 5 months of osimertinib treatment. Assay of plasma ctDNA at this time revealed these different secondary resistance mutations all in trans with each other including distinct mutations at the same codon producing different amino acid changes: G796S/R (mutant allele frequency [MAF]; 14.4%), C797S/G (MAF: 2.26%), L792F/H (MAF: 0.36%), and V802F (MAF: 0.40%), in addition to the pre-existing L858R (MAF:17.9%) and T790M (MAF:18.2%) but all in cis with T790M. The G796S/R mutations are homologous with known reported solvent front mutations in ALK G1202R, ROS1 G2032R, TrkA G595R and TrkC G623R, all of which are associated with acquired resistance to type I TKIs. In silico modeling revealed mutation at G796 interferes with osimertinib binding to the EGFR kinase domain at the phenyl aromatic ring position as this residue forms a narrow "hydrophobic sandwich" with L718, while L792F/H mutation interferes with osimertinib binding at the methoxyl group on the phenyl ring. Multiple resistance mutations at differing allele frequencies including novel EGFR solvent front mutations can emerge in a single patient with progression on osimertinib potentially due to tumor hetereogeneity and definitely present a

Inhibitory Effect of Hizikia fusiformis Solvent-Partitioned Fractions on Invasion and MMP Activity of HT1080 Human Fibrosarcoma Cells

PubMed Central

Lee, Seul-Gi; Karadeniz, Fatih; Oh, Jung Hwan; Yu, Ga Hyun; Kong, Chang-Suk

2017-01-01

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, H2O, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the H2O fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts. PMID:29043215

Potential PM2.5 impacts of festival-related burning and other inputs on air quality in an urban area of southern Taiwan.

PubMed

Tsai, Ying I; Sopajaree, Khajornsak; Kuo, Su-Ching; Yu, Sung-Po

2015-09-15

The Mid-Autumn Festival (MAF), or Moon Festival, is a harvest festival in Taiwan, celebrated by families across the island with evening barbecues outside. This study investigated the potential impact of these activities on the air quality in Tainan, a city in southern Taiwan. Fine particulate matter (PM2.5) was examined in the period leading up to the MAF (pre-MAF), during the Festival (MAF), after the Festival (post-MAF), and in the period after this (a period of moderate air quality: MAQ). Gaseous pollutants in PM2.5 were, from highest to lowest mean concentration, NH3, SO2, HCl, HNO3, HNO2, and oxalic acid, while inorganic salts were mainly in the form of the photochemical products SO4(2-), NH4(+), and NO3(-). These inorganic salts accounted for 37.6%-44.5% of the PM2.5 mass concentration, while a further 26.3%-42.8% of the PM2.5 mass was total carbon (TC). TC was mostly composed of organic carbon (OC) produced by photochemical reactions. Of this, 9.8%-14.9% was carboxylates, of which oxalate was the most abundant compound, accounting for 22.8%-31.9% of carboxylates. The presence of phthalates in the PM2.5 indicated emissions from the plastics industry. Although a noticeable amount of aerosol was produced by festival activities and burning of softwood and hardwood, onshore air currents during the festival prevented potential high aerosol loading. During the moderate air quality period following post-MAF, the concentration of total carbohydrates was 1.44-2.64 times the amount during the festival. Levoglucosan and myo-inositol accounted for 81.7%-89.6% of the total carbohydrate concentration. The average Levo/Manno ratio was 18.64 ± 5.24. The concentration of levoglucosan was closely related to that of PO4(3-), erythritol, and galactose. Backward trajectories indicated that biomass burning in China affected the air quality of Tainan City. Copyright © 2015 Elsevier B.V. All rights reserved.

Establishment and characterization of a fin cell line from blunt snout bream, Megalobrama amblycephala.

PubMed

Zhu, Dong-Mei; Yang, Kun; Wang, Wei-Min; Song, Wen

2013-12-01

This study established and characterized a new cell line (MAF) from the fin of blunt snout bream (Megalobrama amblycephala), a freshwater fish cultivated in China. MAF cells proliferated well in medium 199 supplemented with 10 % fetal bovine serum at 28 °C and have been subcultured more than 95 times in almost a year. MAF cells were revived at 90-95 % viability after 3-6 months of storage in liquid nitrogen. Karyotyping indicated that the modal chromosome number of MAF cells was 48. The MAF cell line consisted predominantly of fibroblastic and epithelial-like cells from M. amblycephala, which was confirmed by immunofluorescence and mitochondrial 12s rRNA sequencing. Viral susceptibility tests showed that MAF cells were susceptible to infection by snakehead rhabdovirus, spring viremia carp virus, and channel catfish virus, which was demonstrated by the presence of cytopathic effect, high viral titers, and PCR products. Bacterial cytotoxicity studies showed that extracellular products from Aeromonas hydrophila were toxic to MAF cells. Cu²⁺ was also cytotoxic to MAF cells, and the 24-h IC₅₀ value was 144.48 μmol/l. When MAF cells were transfected with pEGFP-N1 plasmid, bright fluorescent signals were observed, and the transfection efficiency reached up to 5 %. These results suggest that the MAF cell line may provide a valuable tool for studying virus pathogenesis, as well as cytotoxicity testing and genetic manipulation studies.

Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen.

PubMed

Kim, Yong-Tae; Kim, Se-kwon; Jeon, You-Jin; Park, Sun Joo

2014-12-01

α-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. α-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of α-enolase. In this study, we report that this peptide competes with cellular α-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer.

Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients.

PubMed

Yamamoto, N; Naraparaju, V R; Srinivasula, S M

1995-11-01

A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a precursor for MAF. Treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of plasma Gc protein was low in 16 (35%) of of these patients. Loss of the MAF precursor activity appeared to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Thus, precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in patient blood can serve as diagnostic and prognostic indices.

Evaluation of (188)Re-labeled NGR-VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts.

PubMed

Ma, Wenhui; Shao, Yahui; Yang, Weidong; Li, Guiyu; Zhang, Yingqi; Zhang, Mingru; Zuo, Changjing; Chen, Kai; Wang, Jing

2016-07-01

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine-glycine-arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR-VEGI fusion protein was prepared and labeled with (188)Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that (188)Re-NGR-VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of (188)Re-NGR-VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR-VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of (188)Re-NGR-VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of (188)Re-NGR-VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that (188)Re-NGR-VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.

Hydrophilic extract from Posidonia oceanica inhibits activity and expression of gelatinases and prevents HT1080 human fibrosarcoma cell line invasion

PubMed Central

Barletta, Emanuela; Ramazzotti, Matteo; Fratianni, Florinda; Pessani, Daniela; Degl'Innocenti, Donatella

2015-01-01

Posidonia oceanica (L.) Delile is an endemic Mediterranean sea-grass distributed in the infralittoral zones, where it forms meadows playing a recognized ecological role in the coastal marine habitat. Although its use as a traditional herbal remedy is poorly documented, recent literature reports interesting pharmacological activities as antidiabetic, antioxidant and vasoprotective. Differently from previous literature, this study presents a hydrophilic extraction method that recovers metabolites that may be tested in biological buffers. We showed for the first time in the highly invasive HT1080 human fibrosarcoma cell line that our hydrophilic extract from P. oceanica was able to strongly decrease gene and protein expression of gelatinases MMP-2 and MMP-9 and to directly inhibit in a dose-dependent manner gelatinolytic activity in vitro. Moreover, we have revealed that our extract strongly inhibited HT1080 cell migration and invasion. Biochemical analysis of the hydrophilic extract showed that catechins were the major constituents with minor contribution of gallic acid, ferulic acid and chlorogenic plus a fraction of uncharacterized phenols. However, if each individual compound was tested independently, none by itself was able to induce a direct inhibition of gelatinases as strong as that observed in total extract, opening up new routes to the identification of novel compounds. These results indicate that our hydrophilic extract from P. oceanica might be a source of new pharmacological natural products for treatment or prevention of several diseases related to an altered MMP-2 and MMP-9 expression. PMID:26176658

Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

PubMed

Schoeler, Natasha E; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A; Mackay, Mark; McMahon, Jacinta M; Scheffer, Ingrid E; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

2015-12-01

In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAF<0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF<0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran-Mantel-Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical performance analysis for CMOS based high resolution detectors.

PubMed

Jain, Amit; Bednarek, Daniel R; Rudin, Stephen

2013-03-06

High resolution imaging capabilities are essential for accurately guiding successful endovascular interventional procedures. Present x-ray imaging detectors are not always adequate due to their inherent limitations. The newly-developed high-resolution micro-angiographic fluoroscope (MAF-CCD) detector has demonstrated excellent clinical image quality; however, further improvement in performance and physical design may be possible using CMOS sensors. We have thus calculated the theoretical performance of two proposed CMOS detectors which may be used as a successor to the MAF. The proposed detectors have a 300 μm thick HL-type CsI phosphor, a 50 μm-pixel CMOS sensor with and without a variable gain light image intensifier (LII), and are designated MAF-CMOS-LII and MAF-CMOS, respectively. For the performance evaluation, linear cascade modeling was used. The detector imaging chains were divided into individual stages characterized by one of the basic processes (quantum gain, binomial selection, stochastic and deterministic blurring, additive noise). Ranges of readout noise and exposure were used to calculate the detectors' MTF and DQE. The MAF-CMOS showed slightly better MTF than the MAF-CMOS-LII, but the MAF-CMOS-LII showed far better DQE, especially for lower exposures. The proposed detectors can have improved MTF and DQE compared with the present high resolution MAF detector. The performance of the MAF-CMOS is excellent for the angiography exposure range; however it is limited at fluoroscopic levels due to additive instrumentation noise. The MAF-CMOS-LII, having the advantage of the variable LII gain, can overcome the noise limitation and hence may perform exceptionally for the full range of required exposures; however, it is more complex and hence more expensive.

Macular auto-fluorescence is a follow-up parameter for cystoids macular edema.

PubMed

Zhang, XinYuan; Gong, XiaoHong; Wang, YanHong; Wang, NingLi

2015-08-01

This study aimed to evaluate if macular autofluorescence (MAF) is a valuable, non-invasive follow-up parameter for cystoid macular edema. A total of 71 eyes (71 cases) with cystoid macular edema (CME) were included in the study. Macular pigment (MP) was evaluated using HRA2 (infrared) IF and FA models. The density of MP was graded into three categories: without, partial, and normal amount of MP. A comparison was made between the baseline (before the first administration) level and at the fourth month, following three consecutive intravitreal lucentis injections every month. The morphology and distribution of MAF, and the density and distribution of MP were regarded as the main outcome measures. At the baseline visit, all eyes with CME had petaloid/irregular-shaped MAF in the macular area (100%). No MAF was detected in the control eyes (0). There was significant difference in MAF between the CME and normal groups (P=0.000). At the fourth monthly visit, normal levels of MP density without MAF was detected in 68 eyes (95.8%) with the best corrected spectacular visual acuity increasing to at least 1 line accordingly. We conclude that macular MAF can be used as a follow-up parameter for patients with CME. MP and MAF can indirectly reflect the fovea cone function.

Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells.

PubMed

Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco

2012-01-01

Searching for additional therapeutic tools to fight breast cancer, we investigated the effects of vitamin D-binding protein-derived macrophage activating factor (DBP-MAF, also known as GcMAF) on a human breast cancer cell line (MCF-7). The effects of DBP-MAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane (CAM) assay. DBP-MAF inhibited human breast cancer cell proliferation and cancer cell-stimulated angiogenesis. MCF-7 cells treated with DBP-MAF predominantly grew in monolayer and appeared to be well adherent to each other and to the well surface. Exposure to DBP-MAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results are consistent with the hypothesis that the known anticancer efficacy of DBP-MAF can be ascribed to different biological properties of the molecule that include inhibition of tumour-induced angiogenesis and direct inhibition of cancer cell proliferation, migration and metastatic potential.

Piroxicam, indomethacin and aspirin action on a murine fibrosarcoma. Effects on tumour-associated and peritoneal macrophages.

PubMed Central

Valdéz, J C; Perdigón, G

1991-01-01

Growth of a methylcholanthrene-induced fibrosarcoma in BALB/c mice was accompanied by an increase in the activation state of tumour-associated macrophages (TAM), as measured by their FcIgG receptor expression, phagocytic index and beta-glucuronidase levels. All of these parameters were markedly higher in TAM than in peritoneal macrophages (PM) derived from the same animal. On the other hand, PM from tumour-bearing mice showed lower activation parameters than PM from normal animals. We also studied the effect on tumour development of three inhibitors of prostaglandin synthesis: indomethacin, piroxicam and aspirin. Intraperitoneal administration of these drugs during 8 d was followed by the regression of palpable tumours. Indomethacin (90 mg/d) induced 45% regression, while with piroxicam (two 400 mg/d doses and six 200 mg/d doses) and aspirin (1 mg/d) 32% and 30% regressions, respectively, were observed. The growth rate of nonregressing tumours, which had reached different volumes by the end of the treatment, was delayed to a similar extent by the three anti-inflammatory non-steroidal drugs (NSAID). With respect to TAM, the treatment did not induce any significant change in their activation state, though both piroxicam and indomethacin increased slightly the TAM number. In contrast, NSAID administration was followed by a remarkable increase in the activation parameters of PM when compared with PM from tumour-bearing mice receiving no treatment. Indeed, these parameters were in some cases higher than those of PM from normal mice. The leukocytosis (60,000/microliters) with neutrophilia (80%) induced by tumour growth on peripheral blood leukocytes (PBL) was reversed by the treatment to values close to normal, in parallel with the reduction of tumour size. A drop in haematocrit was also noted which was most probably a consequence of tumour growth rather than of the treatment. This study reveals that the three NSAID tested have a remarkable antitumour activity, which

Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

DTIC Science & Technology

1989-01-01

Reticuloendothelium Acute leukemia 32.7 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 40.5 M Proton 55 8.0 Brain Glioblastoma 42.9 M Electron 1.6 15.0...Subcutis (Leg) Fibrosarcoma 54.3 M Proton 55 6.0 Subcutis (Leg) Fibrosarcoma 54.5 M Proton 55 6.0 Brain Glioblastoma 54.8 M Electron 1.6 15.0 Kidney...55 4.0 Brain Glioblastoma 93.5 F Proton 55 6.0 Brain Glioblastoma 99.7 M Proton Mixed 12.0 Subcutis (Leg) Fibrosarcoma 108.1 M Proton 55 6.0 Mucosa

Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

DTIC Science & Technology

1990-05-01

Subcutis (Leg) Fibrosarcoma 108.1 M Proton 55 6.0 Mucosa ( Nasal ) Carcinoma 116.4 M Proton 138 5.0 Muscle Sarcoma 122.6 F X-ray 2 5.38 Subcutis (Elbow...55 6.0 Brain Glioblastoma 17.2 M Proton 400 1.0 Reticuloendothelium Acute leukemia 32.7 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 40.5 M Proton...55 8.0 Brain Glioblastoma 42.9 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 54.3 M Proton 55 6.0 Subcutis (Leg) Fibrosarcoma 54.5 M Proton 55 6.0

Impact of QTL minor allele frequency on genomic evaluation using real genotype data and simulated phenotypes in Japanese Black cattle.

PubMed

Uemoto, Yoshinobu; Sasaki, Shinji; Kojima, Takatoshi; Sugimoto, Yoshikazu; Watanabe, Toshio

2015-11-19

Genetic variance that is not captured by single nucleotide polymorphisms (SNPs) is due to imperfect linkage disequilibrium (LD) between SNPs and quantitative trait loci (QTLs), and the extent of LD between SNPs and QTLs depends on different minor allele frequencies (MAF) between them. To evaluate the impact of MAF of QTLs on genomic evaluation, we performed a simulation study using real cattle genotype data. In total, 1368 Japanese Black cattle and 592,034 SNPs (Illumina BovineHD BeadChip) were used. We simulated phenotypes using real genotypes under different scenarios, varying the MAF categories, QTL heritability, number of QTLs, and distribution of QTL effect. After generating true breeding values and phenotypes, QTL heritability was estimated and the prediction accuracy of genomic estimated breeding value (GEBV) was assessed under different SNP densities, prediction models, and population size by a reference-test validation design. The extent of LD between SNPs and QTLs in this population was higher in the QTLs with high MAF than in those with low MAF. The effect of MAF of QTLs depended on the genetic architecture, evaluation strategy, and population size in genomic evaluation. In genetic architecture, genomic evaluation was affected by the MAF of QTLs combined with the QTL heritability and the distribution of QTL effect. The number of QTL was not affected on genomic evaluation if the number of QTL was more than 50. In the evaluation strategy, we showed that different SNP densities and prediction models affect the heritability estimation and genomic prediction and that this depends on the MAF of QTLs. In addition, accurate QTL heritability and GEBV were obtained using denser SNP information and the prediction model accounted for the SNPs with low and high MAFs. In population size, a large sample size is needed to increase the accuracy of GEBV. The MAF of QTL had an impact on heritability estimation and prediction accuracy. Most genetic variance can be captured

Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor.

PubMed

Yamamoto, N; Naraparaju, V R

1997-06-01

Vitamin D3-binding protein (DBP; human DBP is known as Gc protein) is the precursor of macrophage activating factor (MAF). Treatment of mouse DBP with immobilized beta-galactosidase or treatment of human Gc protein with immobilized beta-galactosidase and sialidase generated a remarkably potent MAF, termed DBPMAF or GcMAF, respectively. The domain of Gc protein responsible for macrophage activation was cloned and enzymatically converted to the cloned MAF, designated CdMAF. In Ehrlich ascites tumor-bearing mice, tumor-specific serum alpha-N-acetylgalactosaminidase (NaGalase) activity increased linearly with time as the transplanted tumor cells grew in the peritoneal cavity. Therapeutic effects of DBPMAF, GcMAF, and CdMAF on mice bearing Ehrlich ascites tumor were assessed by survival time, the total tumor cell count in the peritoneal cavity, and serum NaGalase activity. Mice that received a single administration of DBPMAF or GcMAF (100 pg/mouse) on the same day after transplantation of tumor (1 x 10(5) cells) showed a mean survival time of 35 +/- 4 days, whereas tumor-bearing controls had a mean survival time of 16 +/- 2 days. When mice received the second DBPMAF or GcMAF administration at day 4, they survived more than 50 days. Mice that received two DBPMAF administrations, at days 4 and 8 after transplantation of 1 x 10(5) tumor cells, survived up to 32 +/- 4 days. At day 4 posttransplantation, the total tumor cell count in the peritoneal cavity was approximately 5 x 10(5) cells. Mice that received two DBPMAF administrations, at days 0 and 4 after transplantation of 5 x 10(5) tumor cells, also survived up to 32 +/- 4 days, while control mice that received the 5 x 10(5) ascites tumor cells only survived for 14 +/- 2 days. Four DBPMAF, GcMAF, or CdMAF administrations to mice transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals showed an extended survival of at least 90 days and an insignificantly low serum NaGalase level between days 30 and 90.

Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice.

PubMed

Koga, Y; Naraparaju, V R; Yamamoto, N

1999-01-01

Cancerous cells secrete alpha-N-acetylgalactosaminidase (NaGalase) into the blood stream, resulting in deglycosylation of serum vitamin D3-binding protein (known as Gc protein), which is a precursor for macrophage activating factor (MAF). Incubation of Gc protein with immobilized beta-galactosidase and sialidase generates the most potent macrophage activating factor (designated GcMAF). Administration of GcMAF to cancer-bearing hosts can bypass the inactivated MAF precursor and act directly on macrophages for efficient activation. Therapeutic effects of GcMAF on Ehrlich ascites tumor-bearing mice were assessed by survival time and serum NaGalase activity, because serum NaGalase activity was proportional to tumor burden. A single administration of GcMAF (100 pg/mouse) to eight mice on the same day after transplantation of the tumor (5 x 10(5) cells) showed a mean survival time of 21 +/- 3 days for seven mice, with one mouse surviving more than 60 days, whereas tumor-bearing controls had a mean survival time of 13 +/- 2 days. Six of the eight mice that received two GcMAF administrations, at Day 0 and Day 4 after transplantation, survived up to 31 +/- 4 days whereas, the remaining two mice survived for more than 60 days. Further, six of the eight mice that received three GcMAF administrations with 4-day intervals showed an extended survival of at least 60 days, and serum NaGalase levels were as low as those of control mice throughout the survival period. The cure with subthreshold GcMAF-treatments (administered once or twice) of tumor-bearing mice appeared to be a consequence of sustained macrophage activation by inflammation resulting from the macrophage-mediated tumoricidal process. Therefore, a protracted macrophage activation induced by a few administrations of minute amounts of GcMAF eradicated the murine ascites tumor.

Uptake and subcellular distribution of [3H]arachidonic acid in murine fibrosarcoma cells measured by electron microscope autoradiography

PubMed Central

1985-01-01

We have used quantitative electron microscope autoradiography to study uptake and distribution of arachidonate in HSDM1C1 murine fibrosarcoma cells and in EPU-1B, a mutant HSDM1C1 line defective in high affinity arachidonate uptake. Cells were labeled with [3H]arachidonate for 15 min, 40 min, 2 h, or 24 h. Label was found almost exclusively in cellular phospholipids; 92-96% of incorporated radioactivity was retained in cells during fixation and tissue processing. All incorporated radioactivity was found to be associated with cellular membranes. Endoplasmic reticulum (ER) contained the bulk of [3H]arachidonate at all time points in both cell types, while mitochondria, which contain a large portion of cellular membrane, were labeled slowly and to substantially lower specific activity. Plasma membrane (PM) also labeled slowly, achieving a specific activity only one-sixth that of ER at 15 min in HSDM1C1 cells (6% of total label) and one-third of ER in EPU-1B (10% of total label). Nuclear membrane (NM) exhibited the highest specific activity of labeling at 15 min in HSDM1C1 cells (twice that of ER) but was not preferentially labeled in the mutant. Over 24 h, PM label intensity increased to that of ER in both cell lines. However, NM activity diminished in HSDM1C1 cells by 24 h to a small fraction of that in ER. In response to agonists, HSDM1C1 cells release labeled arachidonate for eicosanoid synthesis most readily when they have been labeled for short times. Our results therefore suggest that NM and ER, sites of cyclooxygenase in murine fibroblasts, are probably sources for release of [3H]arachidonate, whereas PM and mitochondria are unlikely to be major sources of eicosanoid precursors. PMID:3926781

Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen

PubMed Central

Kim, Yong-Tae; Kim, Se-kwon; Jeon, You-Jin; Park, Sun Joo

2014-01-01

α-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. α-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of α-enolase. In this study, we report that this peptide competes with cellular α-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer. [BMB Reports 2014; 47(12): 691-696] PMID:24602611

Structure and function of three novel MHC class I antigens derived from a C3H ultraviolet-induced fibrosarcoma

PubMed Central

1986-01-01

The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not found on normal C3H tissue. Here we report the complete DNA sequence of the three novel class I genes encoding these molecules, and describe in detail the recognition of the individual products by tumor-reactive and allospecific CTL. Remarkably, although C3H does not appear to express H-2L locus information, this C3H tumor expresses two distinct antigens, termed A149 and A166, which are extremely homologous to each other and to the H-2Ld antigen from BALB/c. The gene encoding the third novel class I antigen from 1591, A216, is quite homologous to H-2Kk) throughout its 3' end. Since all three of these genes account for polymorphic restriction fragments not found in C3H, it is likely that they were derived by recombination from the endogenous class I genes of C3H. The DNA sequence homology of A149, A166, and H-2Ld is especially significant given the functional conservation observed between the products of these genes. Limited sequence substitutions appear to correlate with some of the discrete serological differences observed between these molecules. In addition, both A149 and A166 crossreact, but to differing extents, with H-2Ld at the level of T cell recognition. Our results are consistent with the view that CTL recognize complex conformational determinants on class I molecules, but extend previous observations by comparing a set of antigens with discrete and overlapping structural and functional differences. PMID:3489061

Advanced Manufacturing at the Marshall Space Flight Center and Application to Ares I and Ares V Launch Vehicles

NASA Technical Reports Server (NTRS)

Carruth, Ralph

2008-01-01

There are various aspects of advanced manufacturing technology development at the field centers of the National Aeronautics and Space Administration (NASA). The Marshall Space Flight Center (MSFC) has been given the assignment to lead the National Center for Advanced Manufacturing (NCAM) at MSFC and pursue advanced development and coordination with other federal agencies for NASA. There are significant activities at the Marshall Center as well as at the Michoud Assembly Facility (MAF) in New Orleans which we operate in conjunction with the University of New Orleans. New manufacturing processes in metals processing, component development, welding operations, composite manufacturing and thermal protection system material and process development will be utilized in the manufacturing of the United States two new launch vehicles, the Ares I and the Ares V. An overview of NCAM will be presented as well as some of the development activities and manufacturing that are ongoing in Ares Upper Stage development. Some of the tools and equipment produced by Italian owned companies and their application in this work will be mentioned.

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties.

PubMed

Wang, Meng-Yu; Nestvold, Janne; Rekdal, Øystein; Kvalheim, Gunnar; Fodstad, Øystein

2017-03-15

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports.

PubMed

Inui, Toshio; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Sakamoto, Norihiro; Mette, Martin

2015-08-01

Gc protein-derived macrophage-activating factor (GcMAF) immunotherapy has been steadily advancing over the last two decades. Oral colostrum macrophage-activating factor (MAF) produced from bovine colostrum has shown high macrophage phagocytic activity. GcMAF-based immunotherapy has a wide application for use in treating many diseases via macrophage activation or for use as supportive therapy. Three case studies demonstrate that oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects. We demonstrate that colostrum MAF shows promising clinical results in patients with infectious diseases and for symptoms of fatigue, which is common in many chronic diseases. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

PubMed

Sumiya, Y U; Inoue, Takahiro; Ishikawa, Mami; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2016-07-01

Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. Macrophage activation states and mechanisms are heterogeneous. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to proinflammatory cytokine downregulation following chronic NOD2 stimulation of human macrophages.

PubMed

Zheng, Shasha; Hedl, Matija; Abraham, Clara

2015-02-15

Microbial-induced cytokine regulation is critical to intestinal immune homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2 (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces cytokines. However, cytokines are attenuated after chronic NOD2 and pattern recognition receptor stimulation of macrophages; similar attenuation is observed in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in regulating chronic pattern recognition receptor stimulation and NOD2-induced outcomes has not been examined. Moreover, TAM receptors have been relatively less investigated in human macrophages. Whereas TAM receptors did not downregulate acute NOD2-induced cytokines in primary human macrophages, they were essential for downregulating signaling and proinflammatory cytokine secretion after chronic NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal tissues. Consistently, TAM expression was increased in human intestinal myeloid-derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-β-dependent TAM upregulation in human macrophages, which, in turn, upregulated suppressor of cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3 expression under TAM knockdown conditions restored chronic NOD2-mediated proinflammatory cytokine downregulation. In contrast to the upregulated proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM-deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to upregulate IL-10 secretion; however, full restoration of MAPK activation under these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore, TAM receptors are critical for

Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion.

PubMed

Mok, Yingting; Pang, Yin Huei; Sanjeev, Jain Sudhanshi; Kuick, Chik Hong; Chang, Kenneth Tou-En

2018-01-01

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

Vitamin D binding protein-macrophage activating factor inhibits HCC in SCID mice.

PubMed

Nonaka, Koichi; Onizuka, Shinya; Ishibashi, Hiromi; Uto, Yoshihiro; Hori, Hitoshi; Nakayama, Toshiyuki; Matsuura, Nariaki; Kanematsu, Takashi; Fujioka, Hikaru

2012-01-01

A high incidence of recurrence after treatment is the most serious problem in hepatocellular carcinoma (HCC). Therefore, a new strategy for the treatment of the disease is needed. The aim of the present study was to investigate whether vitamin D binding protein-macrophage activating factor (DBP-maf) is able to inhibit the growth of HCC. The effects of DBP-maf on endothelial cells and macrophage were evaluated by WST-1 assay and phagocytosis assay, respectively. Human HCC cells (HepG2) were implanted into the dorsum of severe combined immunodeficiency (SCID) mice. These mice were divided into control and DBP-maf treatment groups (n = 10/group). The mice in the treatment group received 40 ng/kg/d of DBP-maf for 21 d. DBP-maf showed anti-proliferative activity against endothelial cells and also activated phagocytosis by macrophages. DBP-maf inhibited the growth of HCC cells (treatment group: 126 ± 18mm(3), untreated group: 1691.5 ± 546.9mm(3), P = 0.0077). Histologic examinations of the tumors revealed the microvessel density was reduced and more macrophage infiltration was demonstrated in the tumor of mice in the treatment group. DBP-maf has at least two novel functions, namely, an anti-angiogenic activity and tumor killing activity through the activation of macrophages. DBP-maf may therefore represent a new strategy for the treatment of HCC. Copyright © 2012 Elsevier Inc. All rights reserved.

Intraabdominal pressure after full abdominoplasty in obese multiparous patients.

PubMed

Al-Basti, Habib B; El-Khatib, Hamdy A; Taha, Ahmed; Sattar, Hisham Abdul; Bener, Abdulbari

2004-06-01

This study measured intraabdominal pressure in morbidly obese and multiparous patients who underwent abdominoplasty with musculoaponeurotic plication. The purpose of this study was to evaluate any potential adverse effect on pulmonary function by virtue of pulmonary function tests and measurement of peak airway pressure. The study included 43 multiparous, morbidly obese women (mean body mass index, 35.8 kg/m2) with a mean age (+/- SD) of 38.6 +/- 7 years. All had full abdominoplasty and repair of the musculoaponeurotic system during the period from June of 1999 to May of 2002. Forty-three morbidly obese multiparous patients were seen over a period of 24 months. Their intraabdominal pressure was estimated by measuring the intravesical pressure before and after repair of severe diastases (divarication) of the rectus abdominis muscles with severely flaccid myofascial component before using a hydrometer connected to a Foley catheter both before and after repair. All patients had pulmonary function checked before and 2 months after the repair. The study confirmed that there are minimal changes on the intraabdominal pressure parameters compared with measurement before and after full abdominoplasty with plication of the rectus muscles, with minimal to negligible changes in the intrathoracic pressure. These changes are clinically and statistically significant (p < 0.0001). The study also recommended the safety of full abdominoplasty and repair of the musculoaponeurotic system in multiparous and morbidly obese patients. Furthermore, no statistically significant difference was found in pulmonary function parameters before and after surgery in patients with a history of bronchial asthma.

Differential effects of trichostatin A on gelatinase A expression in 3T3 fibroblasts and HT-1080 fibrosarcoma cells: implications for use of TSA in cancer therapy.

PubMed

Ailenberg, Menachem; Silverman, Mel

2003-03-07

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor with potential in cancer therapeutics. In a recent communication, we demonstrated that TSA is a selective, potent inhibitor of gelatinase A in 3T3 fibroblasts. In the present study, we extend these observations and examine the effects of TSA in 3T3 fibroblasts compared to HT-1080 fibrosarcoma cells with respect to gelatinase A expression, cell viability, and apoptosis. We find that while expression of gelatinase A in 3T3 fibroblasts is exquisitely sensitive to inhibition by TSA, expression of this enzyme in HT-1080 cells is minimally affected by this compound. Moreover, we show that TSA is pro-apoptotic in HT-1080 cells, but is anti-apoptotic in 3T3 cells. We propose a two-pronged model for the therapeutic action of TSA. On the one hand TSA selectively decreases cancer cell viability, while enhancing the viability of stromal cells. On the other hand, by selectively decreasing gelatinase A expression in stromal but not cancer cells, TSA acts to control metastatic potential by reducing the ability of metastatic cells to recruit stromal cells to secrete gelatinase A.

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

PubMed

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-08-01

α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

Oleic Acid, deglycosylated vitamin D-binding protein, nitric oxide: a molecular triad made lethal to cancer.

PubMed

Ruggiero, Marco; Ward, Emma; Smith, Rodney; Branca, Jacopo J V; Noakes, David; Morucci, Gabriele; Taubmann, Margit; Thyer, Lynda; Pacini, Stefania

2014-07-01

Oleic Acid (OA) has been shown to have anticancer properties mediated by interaction with proteins such as α-lactalbumin and lactoferrins. Therefore, we synthesized complexes of OA and Gc protein-derived macrophage activating factor (GcMAF) that inhibits per se cancer cell proliferation and metastatic potential. We hypothesised that OA-GcMAF complexes could exploit the anticancer properties of both OA and GcMAF in a synergistic manner. We postulated that the stimulating effects of GcMAF on macrophages might lead to release of nitric oxide (NO). Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination with a low-carbohydrate, high-protein diet, fermented milk products containing naturally-produced GcMAF, Vitamin D3, omega-3 fatty acids and low-dose acetylsalicylic acid. Measuring the tumour by ultrasonographic techniques, we observed a decrease of tumour volume of about 25%. These observations demonstrate that OA, GcMAF and NO can be properly combined and specifically delivered to advanced cancer patients with significant effects on immune system stimulation and tumour volume reduction avoiding harmful side-effects. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples

PubMed Central

Wang, Jingwen; Skoog, Tiina; Einarsdottir, Elisabet; Kaartokallio, Tea; Laivuori, Hannele; Grauers, Anna; Gerdhem, Paul; Hytönen, Marjo; Lohi, Hannes; Kere, Juha; Jiao, Hong

2016-01-01

High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies. PMID:27633116

The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancer

DTIC Science & Technology

2009-05-01

fibrosarcoma ),  HeLa   (cervical   carcinoma),   and...carcinoma),  TE671  (human  rhabdomyosarcoma),  2fTGH   cells  (human   fibrosarcoma ),  and  monitored  for  RT  release  for...cervical   carcinoma;   TE671   –   human   rhabdomyosarcoma;   2fTGH   –   human   fibrosarcoma ;  LNCaP  –

A Systematic Review of Studies Using the Multidimensional Assessment of Fatigue Scale.

PubMed

Belza, Basia; Miyawaki, Christina E; Liu, Minhui; Aree-Ue, Suparb; Fessel, Melissa; Minott, Kenya R; Zhang, Xi

2018-04-01

To review how the Multidimensional Assessment of Fatigue (MAF) has been used and evaluate its psychometric properties. We conducted a database search using "multidimensional assessment of fatigue" or "MAF" as key terms from 1993 to 2015, and located 102 studies. Eighty-three were empirical studies and 19 were reviews/evaluations. Research was conducted in 17 countries; 32 diseases were represented. Nine language versions of the MAF were used. The mean of the Global Fatigue Index ranged from 10.9 to 49.4. The MAF was reported to be easy-to-use, had strong reliability and validity, and was used in populations who spoke languages other than English. The MAF is an acceptable assessment tool to measure fatigue and intervention effectiveness in various languages, diseases, and settings across the world.

Antibiotic eluting clay mineral (Laponite®) for wound healing application: an in vitro study.

PubMed

Ghadiri, M; Chrzanowski, W; Rohanizadeh, R

2014-11-01

Different materials in form of sponge, hydrogel and film have been developed and formulated for treating and dressing burn wounds. In this study, the potential of Laponite, a gel forming clay, in combination with an antimicrobial agent (mafenide), as a wound dressing material was tested in vitro. Laponite/mafenide (Lap/Maf) hydrogel was formulated in three different ratios of Lap/Maf 1:1, 1:2, 1:3. Laponite/mafenide/alginate (Lap/Maf/Alg) film was also formulated by combining Lap/Maf gel (1:1) with alginate. Intercalation rate of mafenide into the layers of Laponite nanoparticles and physico-chemical properties, including wound dressing characteristics of materials were studied using various analytical methods. Furthermore, the degradation of materials and the release profile of mafenide were investigated in simulated wound exudates fluid and antibacterial effectiveness of the eluted mafenide was tested on a range of bacterial species. The cytotoxicity of materials was also evaluated in skin fibroblast culture. The results showed that mafenide molecules were intercalated between the nano-sized layers of Laponite. The eluted mafenide showed active antibacterial effects against all three tested bacteria. All intercalated mafenide released from Lap/Maf 1:1 and 1:2 gel formulations and nearly 80% release from 1:3 formulation during test period. No significant difference was observed in release profile of mafenide between Lap/Maf/Alg film and Lap/Maf formulations. Wound dressing tests on Lap/Maf/Alg film showed it is a breathable dressing and has capacity to absorb wound exudates. The study showed that prepared Lap/Maf composite has the potential to be used as an antibiotic eluting gel or film for wound healing application. Additionally, Laponite has shown benefits in wound healing processes by releasing Mg(2+) ions and thereby reducing the cytotoxic effect of mafenide on fibroblast cells.

JPRS Report Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-10

V.F. Shilina; GIGIYENA ISANITARIYA No 10, Oct 87] 14 PHYSIOLOGY Changes in Cerebral Electrical Activity of Cats After Intravenous and...from human fibrosarcoma , was studied and compared to expression in normal human leukocytes and slightly transformed cells from human melanoma line...06508 JPRS-ULS-88-009 10 June 1988 PHYSIOLOGY 15 Changes in Cerebral Electrical Activity of Cats After Intravenous and Cerebroventricular

Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas.

PubMed Central

Johnson, T S; Scholfield, C I; Parry, J; Griffin, M

1998-01-01

Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se, since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage. PMID:9512467

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

PubMed Central

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-01-01

α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients.

PubMed

Yamamoto, N; Naraparaju, V R; Asbell, S O

1996-06-15

Serum vitamin D3-binding protein (Gc protein) can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor of the macrophage activating factor (MAF). Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates an extremely high titered MAF, Gc-MAF. When peripheral blood monocytes/macrophages of 52 patients bearing various types of cancer were incubated with 100 pg/ml of GcMAF, the monocytes/macrophages of all patients were efficiently activated. However, the MAF precursor activity of patient plasma Gc protein was found to be severely reduced in about 25% of this patient population. About 45% of the patients had moderately reduced MAF precursor activities. Loss of the precursor activity was found to be due to deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase detected in the patient's bloodstream. The source of the enzyme appeared to be cancerous cells. Radiation therapy decreased plasma alpha-N-acetylgalactosaminidase activity with concomitant increase of precursor activity. This implies that radiation therapy decreases the number of cancerous cells capable of secreting alpha-N-acetylgalactosaminidase. Both alpha-N-acetylgalactosaminidase activity and MAF precursor activity of Gc protein in patient bloodstream can serve as diagnostic and prognostic indices.

Examining brain structures associated with the motive to achieve success and the motive to avoid failure: A voxel-based morphometry study.

PubMed

Ming, Dan; Chen, Qunlin; Yang, Wenjing; Chen, Rui; Wei, Dongtao; Li, Wenfu; Qiu, Jiang; Xu, Zhan; Zhang, Qinglin

2016-01-01

The motive to achieve success (MAS) and motive to avoid failure (MAF) are two different but classical kinds of achievement motivation. Though many functional magnetic resonance imaging studies have explored functional activation in motivation-related conditions, research has been silent as to the brain structures associated with individual differences in achievement motivation, especially with respect to MAS and MAF. In this study, the voxel-based morphometry method was used to uncover focal differences in brain structures related to MAS and MAF measured by the Mehrabian Achieving Tendency Scale in 353 healthy young Chinese adults. The results showed that the brain structures associated with individual differences in MAS and MAF were distinct. MAS was negatively correlated with regional gray matter volume (rGMV) in the medial prefrontal cortex (mPFC)/orbitofrontal cortex while MAF was negatively correlated with rGMV in the mPFC/subgenual cingulate gyrus. After controlling for mutual influences of MAS and MAF scores, MAS scores were found to be related to rGMV in the mPFC/orbitofrontal cortex and another cluster containing the parahippocampal gyrus and precuneus. These results may predict that compared with MAF, the generation process of MAS may be more complex and rational, thus in the real world, perhaps MAS is more beneficial to personal growth and guaranteeing the quality of task performance.

A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

PubMed

Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

1994-05-15

Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

Methylammonium formate as a mobile phase modifier for reversed-phase liquid chromatography

PubMed Central

Grossman, Shau; Danielson, Neil D.

2009-01-01

Although alkylammonium ionic liquids such as ethylammonium nitrate and ethylammonium formate have been used as mobile phase “solvents” for liquid chromatography (LC), we have shown that methylammonium formate (MAF), in part because of its lower viscosity, can be an effective replacement for methanol (MeOH) in reversed-phase LC. Plots of log retention factor versus the fraction of MeOH and MAF in the mobile phase indicate quite comparable solvent strength slope values of 2.50 and 2.05, respectively. Using a polar endcapped C18 column, furazolidone and nitrofurantoin using 20% MAF-80% water could be separated in 22 min but no baseline separation was possible using MeOH as the modifier, even down to 10%. Suppression of silanol peak broadening effects by MAF is important permitting a baseline separation of pyridoxine, thiamine, and nicotinamide using 5% MAF-95% water at 0.7 mL/min. Using 5% MeOH-95% water, severe peak broadening for thiamine is evident. The compatibility of MAF as a mobile phase modifer for LC with mass spectrometry detection of water soluble vitamins is also shown. PMID:18849044

Comparative uptake of ¹⁸F-FEN-DPAZn2, ¹⁸F-FECH, ¹⁸F-fluoride, and ¹⁸F-FDG in fibrosarcoma and aseptic inflammation.

PubMed

Liang, Xiang; Tang, Ganghua; Wang, Hongliang; Hu, Kongzhen; Tang, Xiaolan; Nie, Dahong; Sun, Ting; Huang, Tingting

2014-08-01

The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)-dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the combined S180 fibrosarcoma and turpentine-induced inflammation mice models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation-to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the best selectivity to inflammation. (18)F-FECH positron emission tomography (PET) imaging demonstrates some advantages over (18)F-FDG PET for the differentiation of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for PET imaging of aseptic inflammation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

PubMed

Behrangrad, Shabnam; Kordi Yoosefinejad, Amin

2018-03-01

The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

The Evolution of Host Mitochondrial Association and its Impact on Toxoplasma gondii Infection

NASA Astrophysics Data System (ADS)

English, Elizabeth D.

The association of intracellular pathogens with host mitochondria has been observed across taxa, from bacterial pathogens, such as Legionella pneumophila and Chlamydia trachomati, to the eukaryotic pathogen Toxoplasma gondii. However the functional impact of host mitochondrial association (HMA) remains difficult to assess in most of these species because in many cases the genes responsible for this phenomenon have not yet been identified. The recent discovery of the T. gondii gene responsible for HMA, Mitochondrial Association Factor 1 ( MAF1) has provided us with the tools to begin to understand the evolution and impact of HMA. Here we use multispecies sequence analysis to determine that the MAF1 locus is tandemly duplicated and diversified in both T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative Neospora caninum. Using cross-species complementation we find that T. gondii and H. hammondi harbor copies of MAF1 able to mediate HMA, while N. caninum does not. We have begun mutational analysis using naturally occurring HMA+ and HMA- paralogs of MAF1 in order to determine the portions of MAF1 protein necessary for HMA. Additionally, we have identified the first in vivo phenotypes associated with HMA using multiple mouse models, for both acute and chronic infection. Taken together these data indicate that HMA likely evolved via neofunctionalization of a duplicated ancestral MAF1 gene, and that the neofunctionalized, HMA competent copy of MAF1 provides a selective advantage.

A novel assay system for macrophage-activating factor activity using a human U937 cell line.

PubMed

Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2014-08-01

Macrophages play important roles in antitumor immunity, and immunotherapy with the group-specific component protein-derived macrophage-activating factor (GcMAF) has been reported to be effective in patients with various types of cancers. However, in macrophage research, it is important to properly evaluate macrophage activity. U937 macrophages were induced by 12-O-tetradecanoyl-13-phorbolacetate (TPA). The phagocytic activity of macrophages was evaluated as the internalized beads ratio. The MAF activity was assessed at 30 min after MAF addition as the activation ratio. We established a novel assay for phagocytic activities using differentiated U937 macrophages. The novel protocol was simple and rapid and was sensitive for GcMAF. This protocol should be useful not only for basic studies, such as those on molecular mechanisms underlying macrophage activation, but also for clinical studies, such as assessment of GcMAF activity prior to clinical use. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Reprogramming of Pancreatic Exocrine Cells AR42J Into Insulin-producing Cells Using mRNAs for Pdx1, Ngn3, and MafA Transcription Factors.

PubMed

Koblas, Tomas; Leontovyc, Ivan; Loukotova, Sarka; Kosinova, Lucie; Saudek, Frantisek

2016-05-17

Direct reprogramming of pancreatic nonendocrine cells into insulin-producing β-cells represents a promising approach for the treatment of insulin-dependent diabetes. However, its clinical application is limited by the potential for insertional mutagenesis associated with the viral vectors currently used for cell reprogramming. With the aim of developing a nonintegrative reprogramming strategy for derivation of insulin-producing cells, here, we evaluated a new approach utilizing synthetic messenger RNAs encoding reprogramming transcription factors. Administration of synthetic mRNAs encoding three key transcription regulators of β-cell differentiation-Pdx1, Neurogenin3, and MafA-efficiently reprogrammed the pancreatic exocrine cells into insulin-producing cells. In addition to the insulin genes expression, the synthetic mRNAs also induced the expressions of genes important for proper pancreatic β-cell function, including Sur1, Kir6.2, Pcsk1, and Pcsk2. Pretreating cells with the chromatin-modifying agent 5-Aza-2'-deoxycytidine further enhanced reprogramming efficiency, increasing the proportion of insulin-producing cells from 3.5 ± 0.9 to 14.3 ± 1.9% (n = 4). Moreover, 5-Aza-2'-deoxycytidine pretreatment enabled the reprogrammed cells to respond to glucose challenge with increased insulin secretion. In conclusion, our results support that the reprogramming of pancreatic exocrine cells into insulin-producing cells, induced by synthetic mRNAs encoding pancreatic transcription factors, represents a promising approach for cell-based diabetes therapy.

Black tea high-molecular-weight polyphenol stimulates exercise training-induced improvement of endurance capacity in mouse via the link between AMPK and GLUT4.

PubMed

Eguchi, Tomoaki; Kumagai, Chiaki; Fujihara, Takashi; Takemasa, Thoru; Ozawa, Tetsuo; Numata, Osamu

2013-01-01

Aerobic exercise can promote "fast-to-slow transition" in skeletal muscles, i.e. an increase in oxidative fibers, mitochondria, and myoglobin and improvement in glucose and lipid metabolism. Here, we found that mice administered Mitochondria Activation Factor (MAF) combined with exercise training could run longer distances and for a longer time compared with the exercise only group; MAF is a high-molecular-weight polyphenol purified from black tea. Furthermore, MAF intake combined with exercise training increased phosphorylation of AMPK and mRNA level of glucose transporter 4 (GLUT4). Thus, our data demonstrate for the first time that MAF activates exercise training-induced intracellular signaling pathways that involve AMPK, and improves endurance capacity.

Growth regulators in connective tissue. Systemic administration of an aortic extract inhibits tumor growth in mice.

PubMed Central

Eisenstein, R.; Schumacher, B.; Meineke, C.; Matijevitch, B.; Kuettner, K. E.

1978-01-01

A low-molecular-weight fraction prepared from extracts of bovine aorta inhibits the growth of a transplantable mammary tumor and a fibrosarcoma in mice when injected systemically. It also inhibits the growth of the fibrosarcoma in cell culture. The effect on the fibrosarcoma is much more marked than on the mammary tumor. Since the extract is more effective against the fibrosarcoma and is known to inhibit the growth of endothelial cells, it appears that the enhanced effect on this tumor is due to its activity on the endothelial cells of the host and the tumor cells themselves. The material injected is enriched in an antiproteinase we have previously isolated, which has anticollagneolytic activity and is presumed to be the effector molecule. Images Figure 1 Figure 2 PMID:645813

RFI to CMS: An Approach to Regulatory Acceptance of Site Remediation Technologies

NASA Technical Reports Server (NTRS)

Rowland, Martin A.

2001-01-01

Lockheed Martin made a smooth transition from RCRA Facility Investigation (RFI) at the National Aeronautics and Space Administrations'(NASA) Michoud Assembly Facility (MA-F) to its Corrective Measures Study (CMS) phase within the RCRA Corrective Action Process. We located trichloroethylene (TCE) contamination that resulted from the manufacture of the Apollo Program Saturn V rocket and the Space Shuttle External Tank, began the cleanup, and identified appropriate technologies for final remedies. This was accomplished by establishing a close working relationship with the state environmental regulatory agency through each step of the process, and resulted in receiving approvals for each of those steps. The agency has designated Lockheed Martin's management of the TCE-contamination at the MAF site as a model for other manufacturing sites in a similar situation. In February 1984, the Louisiana Department of Environmental Quality (LDEQ) issued a compliance order to begin the clean up of groundwater contaminated with TCE. In April 1984 Lockheed Martin began operating a groundwater recovery well to capture the TCE plume. The well not only removes contaminants, but also sustains an inward groundwater hydraulic gradient so that the potential offsite migration of the TCE plume is greatly diminished. This effort was successful, and for the agency to give orders and for a regulated industry to follow them is standard procedure, but this is a passive approach to solving environmental problems. The goal of the company thereafter was to take a leadership, proactive role and guide the MAF contamination clean up to its best conclusion at minimum time and lowest cost to NASA. To accomplish this goal, we have established a positive working relationship with LDEQ, involving them interactively in the implementation of advanced remedial activities at MAF as outlined in the following paragraphs.

Application of the diffusive gradients in thin films technique for available potassium measurement in agricultural soils: effects of competing cations on potassium uptake by the resin gel.

PubMed

Zhang, Yulin; Mason, Sean; McNeill, Ann; McLaughlin, Michael J

2014-09-09

The utilization of Amberlite (IRP-69 ion-exchange resin, 100-500 wet mesh) as the binding phase in the diffusive gradients in thin films (DGT) technique has shown potential to improve the assessment of plant-available K in soils. The binding phase has recently been optimized by using a mixed Amberlite and ferrihydrite (MAF) gel which results in linear K uptake over extended deployment periods and in solutions with higher K concentrations. As restriction of K uptake by Ca on the Amberlite based resin gel has been previously proposed, potential competing effects of Ca(2+), Mg(2+) and NH(4+) on K uptake by the MAF gel were investigated. These cations had no effect on K elution efficiency which was 85%. However, K uptake by the MAF gel was restricted in the presence of competing cations in solution. Consequently, the diffusion coefficient of K decreased in the presence of cations compared to previous studies but was stable at 1.12×10(-5)cm(2)s(-1) at 25°C regardless of cation concentrations. Uptake of K by the DGT device was affected by the presence of excessive Ca in more than 30% of twenty typical Australian agricultural soils. However, this problem could be circumvented by using a shorter deployment time than the normal 24 h. Moderate correlation of concentrations of K extracted by DGT with Colwell K (extracted by NaHCO(3), R(2)=0.69) and NH4OAc K (R(2)=0.61) indicates that DGT measures a different pool of K in soils than that measured by the standard extractants used. In addition, the MAF gel has the ability to measure Ca and Mg simultaneously. Copyright © 2014 Elsevier B.V. All rights reserved.

Lost in Translation: Bioinformatic Analysis of Variations Affecting the Translation Initiation Codon in the Human Genome.

PubMed

Abad, Francisco; de la Morena-Barrio, María Eugenia; Fernández-Breis, Jesualdo Tomás; Corral, Javier

2018-06-01

Translation is a key biological process controlled in eukaryotes by the initiation AUG codon. Variations affecting this codon may have pathological consequences by disturbing the correct initiation of translation. Unfortunately, there is no systematic study describing these variations in the human genome. Moreover, we aimed to develop new tools for in silico prediction of the pathogenicity of gene variations affecting AUG codons, because to date, these gene defects have been wrongly classified as missense. Whole-exome analysis revealed the mean of 12 gene variations per person affecting initiation codons, mostly with high (> 0:01) minor allele frequency (MAF). Moreover, analysis of Ensembl data (December 2017) revealed 11,261 genetic variations affecting the initiation AUG codon of 7,205 genes. Most of these variations (99.5%) have low or unknown MAF, probably reflecting deleterious consequences. Only 62 variations had high MAF. Genetic variations with high MAF had closer alternative AUG downstream codons than did those with low MAF. Besides, the high-MAF group better maintained both the signal peptide and reading frame. These differentiating elements could help to determine the pathogenicity of this kind of variation. Data and scripts in Perl and R are freely available at https://github.com/fanavarro/hemodonacion. jfernand@um.es. Supplementary data are available at Bioinformatics online.

Graphics Processing Unit (GPU) implementation of image processing algorithms to improve system performance of the Control, Acquisition, Processing, and Image Display System (CAPIDS) of the Micro-Angiographic Fluoroscope (MAF).

PubMed

Vasan, S N Swetadri; Ionita, Ciprian N; Titus, A H; Cartwright, A N; Bednarek, D R; Rudin, S

2012-02-23

We present the image processing upgrades implemented on a Graphics Processing Unit (GPU) in the Control, Acquisition, Processing, and Image Display System (CAPIDS) for the custom Micro-Angiographic Fluoroscope (MAF) detector. Most of the image processing currently implemented in the CAPIDS system is pixel independent; that is, the operation on each pixel is the same and the operation on one does not depend upon the result from the operation on the other, allowing the entire image to be processed in parallel. GPU hardware was developed for this kind of massive parallel processing implementation. Thus for an algorithm which has a high amount of parallelism, a GPU implementation is much faster than a CPU implementation. The image processing algorithm upgrades implemented on the CAPIDS system include flat field correction, temporal filtering, image subtraction, roadmap mask generation and display window and leveling. A comparison between the previous and the upgraded version of CAPIDS has been presented, to demonstrate how the improvement is achieved. By performing the image processing on a GPU, significant improvements (with respect to timing or frame rate) have been achieved, including stable operation of the system at 30 fps during a fluoroscopy run, a DSA run, a roadmap procedure and automatic image windowing and leveling during each frame.

Developing and testing a global-scale regression model to quantify mean annual streamflow

NASA Astrophysics Data System (ADS)

Barbarossa, Valerio; Huijbregts, Mark A. J.; Hendriks, A. Jan; Beusen, Arthur H. W.; Clavreul, Julie; King, Henry; Schipper, Aafke M.

2017-01-01

Quantifying mean annual flow of rivers (MAF) at ungauged sites is essential for assessments of global water supply, ecosystem integrity and water footprints. MAF can be quantified with spatially explicit process-based models, which might be overly time-consuming and data-intensive for this purpose, or with empirical regression models that predict MAF based on climate and catchment characteristics. Yet, regression models have mostly been developed at a regional scale and the extent to which they can be extrapolated to other regions is not known. In this study, we developed a global-scale regression model for MAF based on a dataset unprecedented in size, using observations of discharge and catchment characteristics from 1885 catchments worldwide, measuring between 2 and 106 km2. In addition, we compared the performance of the regression model with the predictive ability of the spatially explicit global hydrological model PCR-GLOBWB by comparing results from both models to independent measurements. We obtained a regression model explaining 89% of the variance in MAF based on catchment area and catchment averaged mean annual precipitation and air temperature, slope and elevation. The regression model performed better than PCR-GLOBWB for the prediction of MAF, as root-mean-square error (RMSE) values were lower (0.29-0.38 compared to 0.49-0.57) and the modified index of agreement (d) was higher (0.80-0.83 compared to 0.72-0.75). Our regression model can be applied globally to estimate MAF at any point of the river network, thus providing a feasible alternative to spatially explicit process-based global hydrological models.

Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus.

PubMed

Yamamoto, N; Naraparaju, V R; Moore, M; Brent, L H

1997-03-01

A serum glycoprotein, Gc protein (vitamin D3-binding protein), can be converted by beta-galactosidase of B cells and sialidase of T cells to a potent macrophage-activating factor (MAF), a protein with N-acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is the precursor for MAF. Treatment of Gc protein with immobilized beta-galactosidase and sialidase generates a remarkably high titered macrophage-activating factor (GcMAF). When peripheral blood monocytes/ macrophages (designated macrophages) of 33 systemic lupus erythematosus patients were incubated with GcMAF (100 pg/ml), the macrophages of all patients were activated as determined by superoxide generation. However, the precursor activity of patient plasma Gc protein was lost or reduced in these patients. Loss of the precursor activity was the result of deglycosylation of plasma Gc protein by alpha-N-acetylgalactosaminidase activity found in the patient plasma. Levels of plasma alpha-N-acetylgalactosaminidase activity in individual patients had an inverse correlation with the MAF precursor activity of their plasma Gc protein. Deglycosylated Gc protein cannot be converted to macro-phage-activating factor. The resulting defect in macro-phage activation may lead to an inability to clear pathogenic immune complexes. Thus, elevated plasma alpha-N-acetylgalactosaminidase activity resulting in the loss of MAF precursor activity and reduced macro-phage activity may play a role in the pathogenesis of systemic lupus erythematosus.

A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages.

PubMed

Thyer, Lynda; Ward, Emma; Smith, Rodney; Fiore, Maria Giulia; Magherini, Stefano; Branca, Jacopo J V; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco; Pacini, Stefania

2013-07-08

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This allows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects.

Aldosterone induces clonal β-cell failure through glucocorticoid receptor

PubMed Central

Chen, Fang; Liu, Jia; Wang, Yanyang; Wu, Tijun; Shan, Wei; Zhu, Yunxia; Han, Xiao

2015-01-01

Aldosterone excess causes insulin resistance in peripheral tissues and directly impairs the function of clonal β-cell. The aim of this study was to investigate the molecular mechanisms involved in the aldosterone-induced impairment of clonal β-cells. As expected, aldosterone induced apoptosis and β-cell dysfunction, including impairment of insulin synthesis and secretion, which were reversed by Glucocorticoid receptor (GR) antagonists or GR-specific siRNA. However, mineralocorticoid receptor (MR) antagonists or MR-specific siRNA had no effect on impairment of clonal β-cells induced by aldosterone. Besides, aldosterone significantly decreased expression and activity of MafA, while activated JNK and p38 MAPK in a GR-dependent manner. In addition, JNK inhibitors (SP600125) and/or p38 inhibitors (SB203580) could abolish the effect of aldosterone on MafA expression and activity. Importantly, overexpression of JNK1 or p38 reversed the protective effect of a GR antagonist on the decrease of MafA expression and activity. Furthermore, aldosterone inhibits MafA expression at the transcriptional and post-transcriptional level through activation of JNK and p38, respectively. Consequently, overexpression of MafA increased synthesis and secretion of insulin, and decreased apoptosis in clonal β-cells exposed to aldosterone. These findings identified aldosterone as an inducer of clonal β-cell failure that operates through the GR-MAPK-MafA signaling pathway. PMID:26287126

Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

PubMed

Morucci, Gabriele; Branca, Jacopo J V; Gulisano, Massimo; Ruggiero, Marco; Paternostro, Ferdinando; Pacini, Alessandra; Di Cesare Mannelli, Lorenzo; Pacini, Stefania

2015-02-01

Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce

Nasofacial defect following fibrosarcoma excision and radiotherapy.

PubMed

Burget, G L; Panje, W R; Krause, C J

1988-01-01

For initial reconstruction, Dr. Burget suggests that he would have advanced the cheek flap medially toward the nasal septum and, subsequently, reconstructed the missing right half of the nose with a forehead flap and cartilage grafts. Dr. Panje suggested early prosthetic rehabilitation, while Dr. Krause's concepts were similar to Dr. Burget's, with forehead flap nasal reconstruction, after cheek reconstruction to the nasofacial and nasolabial lines with a medially advanced cheek flap. Dr. Panje recommended an immediate maxillary denture prosthesis, as did Dr. Krause (who supplemented this with foam rubber). Dr. Burget placed the prosthesis 3 weeks after tumor ablation. For skin grafts, Drs. Panje and Burget suggested split thickness grafts to all new surfaces to decrease wound contracture, while Dr. Krause used dermis grafts for the same purpose. Other reconstructive methods mentioned were the (1) cervical tubed flap, (2) free scapular flap, (3) Washio flap, (4) tissue expansion, and (5) nasolabial flap. Suggestions for isolated defects included: Lower eyelid--increase internal support by building up the prosthesis; release lower lid from deltopectoral flap and V-Y advancement; support graft or irradiated cartilage (1-2 mm sheet) under orbicularis oculi. Nasal ala--bring present ala down and insert cartilage graft; turn internal skin down and fill the resulting defect with a composite graft. Upper lip--multiple Z-plasty. Retrodisplacement of cheek due to maxillectomy--release buccal scar; skin graft the raw internal surface and build up prosthesis.

Primary and acquired EGFR T790M-mutant NSCLC patients identified by routine mutation testing show different characteristics but may both respond to osimertinib treatment.

PubMed

Li, Weihua; Qiu, Tian; Guo, Lei; Ling, Yun; Gao, Yibo; Ying, Jianming; He, Jie

2018-06-01

Primary EGFR T790M mutation is occasionally identified by routine mutation testing in tyrosine kinase inhibitor (TKI)-naive patients with non-small cell lung cancer (NSCLC). We herein aimed to compare the characteristics of primary and acquired T790M mutations in NSCLC patients, and their response to osimertinib. Using amplification refractory mutation system (ARMS) detection, primary T790M was identified in 0.5% (46/8723) of TKI-naive patients, whereas acquired T790M was detected in 49.7% (71/143) of TKI-relapsed patients. T790M always coexisted with a sensitizing EGFR mutation. Primary T790M more commonly coexisted with L858R, whereas acquired T790M was more likely to coexist with exon 19 deletions. Moreover, next-generation sequencing (NGS) showed that concomitant sensitizing EGFR and primary T790M mutant allele frequencies (MAFs) were highly concordant, but acquired T790M MAFs were significantly lower than the sensitizing EGFR MAFs. Sixteen acquired T790M-mutant patients received osimertinib. The median progression-free survival (PFS) was 8.1 months. Four primary T790M-mutant patients received osimertinib and the median PFS was 8.0 months. Together, our study demonstrates that primary and acquired T790M-mutant patients show distinct differences in some clinical and molecular characteristics, but may both respond to osimertinib treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats.

PubMed

Benis, K A; Schneider, G B

1996-10-15

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein-macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line.

PubMed

Toyohara, Yukiyo; Hashitani, Susumu; Kishimoto, Hiromitsu; Noguchi, Kazuma; Yamamoto, Nobuto; Urade, Masahiro

2011-07-01

This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model.

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line

PubMed Central

TOYOHARA, YUKIYO; HASHITANI, SUSUMU; KISHIMOTO, HIROMITSU; NOGUCHI, KAZUMA; YAMAMOTO, NOBUTO; URADE, MASAHIRO

2011-01-01

This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model. PMID:22848250

A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages

PubMed Central

Thyer, Lynda; Ward, Emma; Smith, Rodney; Fiore, Maria Giulia; Magherini, Stefano; Branca, Jacopo J. V.; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco; Pacini, Stefania

2013-01-01

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects. PMID:23857228

Identification-While-Scanning of a Multi-Aircraft Formation Based on Sparse Recovery for Narrowband Radar.

PubMed

Jiang, Yuan; Xu, Jia; Peng, Shi-Bao; Mao, Er-Ke; Long, Teng; Peng, Ying-Ning

2016-11-23

It is known that the identification performance of a multi-aircraft formation (MAF) of narrowband radar mainly depends on the time on target (TOT). To realize the identification task in one rotated scan with limited TOT, the paper proposes a novel identification-while-scanning (IWS) method based on sparse recovery to maintain high rotating speed and super-resolution for MAF identification, simultaneously. First, a multiple chirp signal model is established for MAF in a single scan, where different aircraft may have different Doppler centers and Doppler rates. Second, based on the sparsity of MAF in the Doppler parameter space, a novel hierarchical basis pursuit (HBP) method is proposed to obtain satisfactory sparse recovery performance as well as high computational efficiency. Furthermore, the parameter estimation performance of the proposed IWS identification method is analyzed with respect to recovery condition, signal-to-noise ratio and TOT. It is shown that an MAF can be effectively identified via HBP with a TOT of only about one hundred microseconds for IWS applications. Finally, some numerical experiment results are provided to demonstrate the effectiveness of the proposed method based on both simulated and real measured data.

Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

PubMed

Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

2013-07-01

Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

Modified artificial fish school algorithm for free space optical communication with sensor-less adaptive optics system

NASA Astrophysics Data System (ADS)

Cao, Jingtai; Zhao, Xiaohui; Li, Zhaokun; Liu, Wei; Gu, Haijun

2017-11-01

The performance of free space optical (FSO) communication system is limited by atmospheric turbulent extremely. Adaptive optics (AO) is the significant method to overcome the atmosphere disturbance. Especially, for the strong scintillation effect, the sensor-less AO system plays a major role for compensation. In this paper, a modified artificial fish school (MAFS) algorithm is proposed to compensate the aberrations in the sensor-less AO system. Both the static and dynamic aberrations compensations are analyzed and the performance of FSO communication before and after aberrations compensations is compared. In addition, MAFS algorithm is compared with artificial fish school (AFS) algorithm, stochastic parallel gradient descent (SPGD) algorithm and simulated annealing (SA) algorithm. It is shown that the MAFS algorithm has a higher convergence speed than SPGD algorithm and SA algorithm, and reaches the better convergence value than AFS algorithm, SPGD algorithm and SA algorithm. The sensor-less AO system with MAFS algorithm effectively increases the coupling efficiency at the receiving terminal with fewer numbers of iterations. In conclusion, the MAFS algorithm has great significance for sensor-less AO system to compensate atmospheric turbulence in FSO communication system.

Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma gondii via Neofunctionalization of a Gene Duplicate

PubMed Central

Adomako-Ankomah, Yaw; English, Elizabeth D.; Danielson, Jeffrey J.; Pernas, Lena F.; Parker, Michelle L.; Boulanger, Martin J.; Dubey, Jitender P.; Boyle, Jon P.

2016-01-01

In Toxoplasma gondii, an intracellular parasite of humans and other animals, host mitochondrial association (HMA) is driven by a gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. However, the importance of MAF1 gene duplication in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we used within- and between-species comparative analysis to determine that the MAF1 locus is duplicated in T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative, Neospora caninum. Using cross-species complementation, we determined that the MAF1 locus harbors multiple distinct paralogs that differ in their ability to mediate HMA, and that only T. gondii and H. hammondi harbor HMA+ paralogs. Additionally, we found that exogenous expression of an HMA+ paralog in T. gondii strains that do not normally exhibit HMA provides a competitive advantage over their wild-type counterparts during a mouse infection. These data indicate that HMA likely evolved by neofunctionalization of a duplicate MAF1 copy in the common ancestor of T. gondii and H. hammondi, and that the neofunctionalized gene duplicate is selectively advantageous. PMID:26920761

Characterization of corneal damage from Pseudomonas aeruginosa infection by the use of multiphoton microscopy

NASA Astrophysics Data System (ADS)

Chang, Yu-Lin; Chen, Wei-Liang; Lo, Wen; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

2010-11-01

Using multiphoton autofluorescence (MAF) and second harmonic generation (SHG) microscopy, we investigate the morphology and the structure of the corneal epithelium and stroma collagen of bovine cornea following injection of Pseudomonas aeruginosa. We found that corneal epithelial cells are damaged and stromal collagen becoming increasingly autofluorescent with time. We also characterized infected cornea cultured for 0, 6, 12, and 24 h by quantitative ratiometric MAF to SHG index (MAFSI) analysis. MAFSI results show that the destruction of the stromal collagen corresponds to a decrease in SHG intensity and increase of MAF signal with time.

Architecture of the Suprahyoid Muscles: A Volumetric Musculoaponeurotic Analysis.

PubMed

Shaw, Stephanie M; Martino, Rosemary; Mahdi, Ali; Sawyer, Forrest Kip; Mathur, Sunita; Hope, Andrew; Agur, Anne M

2017-10-17

Suprahyoid muscles play a critical role in swallowing. The arrangement of the fiber bundles and aponeuroses has not been investigated volumetrically, even though muscle architecture is an important determinant of function. Thus, the purpose was to digitize, model in three dimensions, and quantify the architectural parameters of the suprahyoid muscles to determine and compare their relative functional capabilities. Fiber bundles and aponeuroses from 11 formalin-embalmed specimens were serially dissected and digitized in situ. Data were reconstructed in three dimensions using Autodesk Maya. Architectural parameters were quantified, and data were compared using independent samples t-tests and analyses of variance. Based on architecture and attachment sites, suprahyoid muscles were divided into 3 groups: anteromedial, superolateral, and superoposterior. Architectural parameters differed significantly (p < .05) across muscles and across the 3 groups, suggesting differential roles in hyoid movement during swallowing. When activated simultaneously, anteromedial and superoposterior muscle groups could work together to elevate the hyoid. The results suggest that the suprahyoid muscles can have individualized roles in hyoid excursion during swallowing. Muscle balance may be important for identifying and treating hyolaryngeal dysfunction in patients with dysphagia.

Architecture of the Suprahyoid Muscles: A Volumetric Musculoaponeurotic Analysis

ERIC Educational Resources Information Center

Shaw, Stephanie M.; Martino, Rosemary; Mahdi, Ali; Sawyer, Forrest Kip; Mathur, Sunita; Hope, Andrew; Agur, Anne M.

2017-01-01

Purpose: Suprahyoid muscles play a critical role in swallowing. The arrangement of the fiber bundles and aponeuroses has not been investigated volumetrically, even though muscle architecture is an important determinant of function. Thus, the purpose was to digitize, model in three dimensions, and quantify the architectural parameters of the…

Acute molecular response of mouse hindlimb muscles to chronic stimulation.

PubMed

LaFramboise, W A; Jayaraman, R C; Bombach, K L; Ankrapp, D P; Krill-Burger, J M; Sciulli, C M; Petrosko, P; Wiseman, R W

2009-09-01

Stimulation of the mouse hindlimb via the sciatic nerve was performed for a 4-h period to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 +/- 0.1 g/g body wt) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon study completion. An immediate-early growth response was present in the extensor digitorum longus (EDL) muscle (FOS, JUN, activating transcription factor 3, and musculoaponeurotic fibrosarcoma oncogene) with a similar but attenuated pattern in the soleus muscle. Transcript profiles showed decreased fast fiber-specific mRNA (myosin heavy chains 2A and 2B, fast troponins T(3) and I, alpha-tropomyosin, muscle creatine kinase, and parvalbumin) and increased slow transcripts (myosin heavy chain-1beta/slow, troponin C slow, and tropomyosin 3y) in the EDL versus soleus muscles. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration in stimulated versus control muscles, whereas ultrastructural analysis showed no evidence of myofiber damage after stimulation. Multiple fiber type-specific transcription factors (tea domain family member 1, nuclear factor of activated T cells 1, peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta, circadian locomotor output cycles kaput, and hypoxia-inducible factor-1alpha) increased in the EDL along with transcription factors characteristic of embryogenesis (Kruppel-like factor 4; SRY box containing 17; transcription factor 15; PBX/knotted 1 homeobox 1; and embryonic lethal, abnormal vision). No established in vivo satellite cell markers or genes activated in our parallel experiments of satellite cell proliferation in vitro (cyclins A(2), B(2), C, and E(1) and MyoD) were differentially increased in the stimulated muscles. These results indicated that the molecular onset of fast to slow phenotype conversion occurred in the EDL within

Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam

PubMed Central

Panchal, Trupti; Chen, Xi; Poon, James; Kouptsova, Jane

2017-01-01

Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2–3 germline stem cells. In particular, we focused on the question of how cap cells form. Cap cells express Tj and are considered the key component of a mature germline stem cell niche. We conclude that Tj controls the specification of cap cells, as the complete loss of Tj function caused the development of additional terminal filament cells at the expense of cap cells, and terminal filament cells developed cap cell characteristics when induced to express Tj. Further, we propose that Tj controls the morphogenetic behavior of cap cells as they adopted the shape and spatial organization of terminal filament cells but otherwise appeared to retain their fate when Tj expression was only partially reduced. Our data indicate that Tj contributes to the establishment of germline stem cells by promoting the cap cell fate, and controls the stem cell-carrying capacity of the niche by regulating niche architecture. Analysis of the interactions between Tj and the Notch (N) pathway indicates that Tj and N have distinct functions in the cap cell specification program. We propose that formation of cap cells depends on the combined activities of Tj and the N pathway, with Tj promoting the cap cell fate by blocking the terminal filament cell fate, and N supporting cap cells by preventing the escort cell fate and/or controlling the number of cap cell precursors. PMID:28542174

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

PubMed

Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D

2017-09-01

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting

PubMed Central

Khan, Tarik A.; Friedensohn, Simon; de Vries, Arthur R. Gorter; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T.

2016-01-01

High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion—the intraclonal diversity index—which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology. PMID:26998518

Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting.

PubMed

Khan, Tarik A; Friedensohn, Simon; Gorter de Vries, Arthur R; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T

2016-03-01

High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology.

Whole-genome sequence-based analysis of thyroid function.

PubMed

Taylor, Peter N; Porcu, Eleonora; Chew, Shelby; Campbell, Purdey J; Traglia, Michela; Brown, Suzanne J; Mullin, Benjamin H; Shihab, Hashem A; Min, Josine; Walter, Klaudia; Memari, Yasin; Huang, Jie; Barnes, Michael R; Beilby, John P; Charoen, Pimphen; Danecek, Petr; Dudbridge, Frank; Forgetta, Vincenzo; Greenwood, Celia; Grundberg, Elin; Johnson, Andrew D; Hui, Jennie; Lim, Ee M; McCarthy, Shane; Muddyman, Dawn; Panicker, Vijay; Perry, John R B; Bell, Jordana T; Yuan, Wei; Relton, Caroline; Gaunt, Tom; Schlessinger, David; Abecasis, Goncalo; Cucca, Francesco; Surdulescu, Gabriela L; Woltersdorf, Wolfram; Zeggini, Eleftheria; Zheng, Hou-Feng; Toniolo, Daniela; Dayan, Colin M; Naitza, Silvia; Walsh, John P; Spector, Tim; Davey Smith, George; Durbin, Richard; Richards, J Brent; Sanna, Serena; Soranzo, Nicole; Timpson, Nicholas J; Wilson, Scott G

2015-03-06

Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10(-9)) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10(-9)) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10(-11)). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.

Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma gondii via Neofunctionalization of a Gene Duplicate.

PubMed

Adomako-Ankomah, Yaw; English, Elizabeth D; Danielson, Jeffrey J; Pernas, Lena F; Parker, Michelle L; Boulanger, Martin J; Dubey, Jitender P; Boyle, Jon P

2016-05-01

In Toxoplasma gondii, an intracellular parasite of humans and other animals, host mitochondrial association (HMA) is driven by a gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. However, the importance of MAF1 gene duplication in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we used within- and between-species comparative analysis to determine that the MAF1 locus is duplicated in T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative, Neospora caninum Using cross-species complementation, we determined that the MAF1 locus harbors multiple distinct paralogs that differ in their ability to mediate HMA, and that only T. gondii and H. hammondi harbor HMA(+) paralogs. Additionally, we found that exogenous expression of an HMA(+) paralog in T. gondii strains that do not normally exhibit HMA provides a competitive advantage over their wild-type counterparts during a mouse infection. These data indicate that HMA likely evolved by neofunctionalization of a duplicate MAF1 copy in the common ancestor of T. gondii and H. hammondi, and that the neofunctionalized gene duplicate is selectively advantageous. Copyright © 2016 by the Genetics Society of America.

RNA Polymerase III Output Is Functionally Linked to tRNA Dimethyl-G26 Modification

PubMed Central

Arimbasseri, Aneeshkumar G.; Blewett, Nathan H.; Iben, James R.; Lamichhane, Tek N.; Cherkasova, Vera; Hafner, Markus; Maraia, Richard J.

2015-01-01

Control of the differential abundance or activity of tRNAs can be important determinants of gene regulation. RNA polymerase (RNAP) III synthesizes all tRNAs in eukaryotes and it derepression is associated with cancer. Maf1 is a conserved general repressor of RNAP III under the control of the target of rapamycin (TOR) that acts to integrate transcriptional output and protein synthetic demand toward metabolic economy. Studies in budding yeast have indicated that the global tRNA gene activation that occurs with derepression of RNAP III via maf1-deletion is accompanied by a paradoxical loss of tRNA-mediated nonsense suppressor activity, manifested as an antisuppression phenotype, by an unknown mechanism. We show that maf1-antisuppression also occurs in the fission yeast S. pombe amidst general activation of RNAP III. We used tRNA-HydroSeq to document that little changes occurred in the relative levels of different tRNAs in maf1Δ cells. By contrast, the efficiency of N2,N2-dimethyl G26 (m2 2G26) modification on certain tRNAs was decreased in response to maf1-deletion and associated with antisuppression, and was validated by other methods. Over-expression of Trm1, which produces m2 2G26, reversed maf1-antisuppression. A model that emerges is that competition by increased tRNA levels in maf1Δ cells leads to m2 2G26 hypomodification due to limiting Trm1, reducing the activity of suppressor-tRNASerUCA and accounting for antisuppression. Consistent with this, we show that RNAP III mutations associated with hypomyelinating leukodystrophy decrease tRNA transcription, increase m2 2G26 efficiency and reverse antisuppression. Extending this more broadly, we show that a decrease in tRNA synthesis by treatment with rapamycin leads to increased m2 2G26 modification and that this response is conserved among highly divergent yeasts and human cells. PMID:26720005

The effect of rare alleles on estimated genomic relationships from whole genome sequence data.

PubMed

Eynard, Sonia E; Windig, Jack J; Leroy, Grégoire; van Binsbergen, Rianne; Calus, Mario P L

2015-03-12

Relationships between individuals and inbreeding coefficients are commonly used for breeding decisions, but may be affected by the type of data used for their estimation. The proportion of variants with low Minor Allele Frequency (MAF) is larger in whole genome sequence (WGS) data compared to Single Nucleotide Polymorphism (SNP) chips. Therefore, WGS data provide true relationships between individuals and may influence breeding decisions and prioritisation for conservation of genetic diversity in livestock. This study identifies differences between relationships and inbreeding coefficients estimated using pedigree, SNP or WGS data for 118 Holstein bulls from the 1000 Bull genomes project. To determine the impact of rare alleles on the estimates we compared three scenarios of MAF restrictions: variants with a MAF higher than 5%, variants with a MAF higher than 1% and variants with a MAF between 1% and 5%. We observed significant differences between estimated relationships and, although less significantly, inbreeding coefficients from pedigree, SNP or WGS data, and between MAF restriction scenarios. Computed correlations between pedigree and genomic relationships, within groups with similar relationships, ranged from negative to moderate for both estimated relationships and inbreeding coefficients, but were high between estimates from SNP and WGS (0.49 to 0.99). Estimated relationships from genomic information exhibited higher variation than from pedigree. Inbreeding coefficients analysis showed that more complete pedigree records lead to higher correlation between inbreeding coefficients from pedigree and genomic data. Finally, estimates and correlations between additive genetic (A) and genomic (G) relationship matrices were lower, and variances of the relationships were larger when accounting for allele frequencies than without accounting for allele frequencies. Using pedigree data or genomic information, and including or excluding variants with a MAF below 5

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats.

PubMed

Kumar, S Selva; Karrunakaran, C M; Rao, M R K; Balasubramanian, M P

2011-01-11

The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties.

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats

PubMed Central

Kumar, S. Selva; Karrunakaran, C. M.; Rao, M. R. K.; Balasubramanian, M. P.

2011-01-01

Background: The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. Materials and Methods: The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. Results: The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. Conclusion: The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties. PMID:21297921

New acute transforming feline retovirus with fms homology specifies a C-terminally truncated version of the c-fms protein that is different from SM-feline sarcoma virus v-fms protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Besmer, P.; Lader, E.; George, P.C.

1986-10-01

The HZ5-feline sarcoma virus (FeSV) is a new acute transforming feline retrovirus which was isolated from a multicentric fibrosarcoma of a domestic cat. The HZ5-FeSV transforms fibroblasts in vitro and is replication defective. A biologically active integrated HZ5-FeSV provirus was molecularly cloned from cellular DNA of HZ5-FeSV-infected FRE-3A rat cells. The HZ5-FeSV has oncogene homology with the fms sequences of the SM-FeSV. The genome organization of the 8.6-kilobase HZ5-FeSV provirus is 5' ..delta..gag-fms-..delta..pol-..delta..env 3'. The HZ5- and SM-FeSVs display indistinguishable in vitro transformation characteristics, and the structures of the gag-fms transforming genes in the two viruses are very similar. Inmore » the HZ5-FeSV and the SM-FeSV, identical c-fms and feline leukemia virus p10 sequences form the 5' gag-fms junction. With regard to v-fms the two viruses are homologous up to 11 amino acids before the C terminus of the SM-FeSV v-fms protein. In HZ5-FeSV a segment of 362 nucleotides then follows before the 3' recombination site with feline leukemia virus pol. The new 3' v-fms sequence encodes 27 amino acids before reaching a TGA termination signal. The relationship of this sequence with the recently characterized human c-fms sequence has been examined. The 3' HZ5-FeSV v-fms sequence is homologous with 3' c-fms sequences. A frameshift mutation (11-base-pair deletion) was found in the C-terminal fms coding sequence of the HZ5-FeSV. As a result, the HZ5-FeSV v-fms protein is predicted to be a C-terminally truncated version of c-fms. This frameshift mutation may determine the oncogenic properties of v-fms in the HZ5-FeSV.« less

Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

PubMed

Yamamoto, N; Naraparaju, V R

1998-06-01

Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.

Design, construction, and evaluation of new high resolution medical imaging detector/systems

NASA Astrophysics Data System (ADS)

Jain, Amit

Increasing need of minimally invasive endovascular image guided interventional procedures (EIGI) for accurate and successful treatment of vascular disease has set a quest for better image quality. Current state of the art detectors are not up to the mark for these complex procedures due to their inherent limitations. Our group has been actively working on the design and construction of a high resolution, region of interest CCD-based X-ray imager for some time. As a part of that endeavor, a Micro-angiographic fluoroscope (MAF) was developed to serve as a high resolution, ROI X-ray imaging detector in conjunction with large lower resolution full field of view (FOV) state-of-the-art x-ray detectors. The newly developed MAF is an indirect x-ray imaging detector capable of providing real-time images with high resolution, high sensitivity, no lag and low instrumentation noise. It consists of a CCD camera coupled to a light image intensifier (LII) through a fiber optic taper. The CsI(Tl) phosphor serving as the front end is coupled to the LII. For this work, the MAF was designed and constructed. The linear system cascade theory was used to evaluate the performance theoretically. Linear system metrics such as MTF and DQE were used to gauge the detector performance experimentally. The capabilities of the MAF as a complete system were tested using generalized linear system metrics. With generalized linear system metrics the effects of finite size focal spot, geometric magnification and the presence of scatter are included in the analysis and study. To minimize the effect of scatter, an anti-scatter grid specially designed for the MAF was also studied. The MAF was compared with the flat panel detector using signal-to-noise ratio and the two dimensional linear system metrics. The signal-to-noise comparison was carried out to point out the effect of pixel size and Point Spread Function of the detector. The two dimensional linear system metrics were used to investigate the

Comparison of Motive to Succeed, Motive to Avoid Failure, and Fear of Success Levels between Male and Female Intercollegiate Swimmers.

ERIC Educational Resources Information Center

Houseworth, Steven; Thirer, Joel

A study investigated sex based differences among intercollegiate athletes for the variables: motive to succeed (Ms), motive to avoid failure (Maf), and fear of success (FOS). Actual athletic competitions were used as target situations to elicit feelings of Ms, Maf, and FOS within each athlete. Mehrabian's scale of achieving tendencies, Martens'…

A new acute transforming feline retrovirus with fms homology specifies a C-terminally truncated version of the c-fms protein that is different from SM-feline sarcoma virus v-fms protein.

PubMed Central

Besmer, P; Lader, E; George, P C; Bergold, P J; Qiu, F H; Zuckerman, E E; Hardy, W D

1986-01-01

The HZ5-feline sarcoma virus (FeSV) is a new acute transforming feline retrovirus which was isolated from a multicentric fibrosarcoma of a domestic cat. The HZ5-FeSV transforms fibroblasts in vitro and is replication defective. A biologically active integrated HZ5-FeSV provirus was molecularly cloned from cellular DNA of HZ5-FeSV-infected FRE-3A rat cells. The HZ5-FeSV has oncogene homology with the fms sequences of the SM-FeSV. The genome organization of the 8.6-kilobase HZ5-FeSV provirus is 5' delta gag-fms-delta pol-delta env 3'. The HZ5-and SM-FeSVs display indistinguishable in vitro transformation characteristics, and the structures of the gag-fms transforming genes in the two viruses are very similar. In the HZ5-FeSV and the SM-FeSV, identical c-fms and feline leukemia virus p10 sequences form the 5' gag-fms junction. With regard to v-fms the two viruses are homologous up to 11 amino acids before the C terminus of the SM-FeSV v-fms protein. In HZ5-FeSV a segment of 362 nucleotides then follows before the 3' recombination site with feline leukemia virus pol. The new 3' v-fms sequence encodes 27 amino acids before reaching a TGA termination signal. The relationship of this sequence with the recently characterized human c-fms sequence has been examined. The 3' HZ5-FeSV v-fms sequence is homologous with 3' c-fms sequences. A frameshift mutation (11-base-pair deletion) was found in the C-terminal fms coding sequence of the HZ5-FeSV. As a result, the HZ5-FeSV v-fms protein is predicted to be a C-terminally truncated version of c-fms. This frameshift mutation may determine the oncogenic properties of v-fms in the HZ5-FeSV. Images PMID:3018286

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes.

PubMed

Albrechtsen, A; Grarup, N; Li, Y; Sparsø, T; Tian, G; Cao, H; Jiang, T; Kim, S Y; Korneliussen, T; Li, Q; Nie, C; Wu, R; Skotte, L; Morris, A P; Ladenvall, C; Cauchi, S; Stančáková, A; Andersen, G; Astrup, A; Banasik, K; Bennett, A J; Bolund, L; Charpentier, G; Chen, Y; Dekker, J M; Doney, A S F; Dorkhan, M; Forsen, T; Frayling, T M; Groves, C J; Gui, Y; Hallmans, G; Hattersley, A T; He, K; Hitman, G A; Holmkvist, J; Huang, S; Jiang, H; Jin, X; Justesen, J M; Kristiansen, K; Kuusisto, J; Lajer, M; Lantieri, O; Li, W; Liang, H; Liao, Q; Liu, X; Ma, T; Ma, X; Manijak, M P; Marre, M; Mokrosiński, J; Morris, A D; Mu, B; Nielsen, A A; Nijpels, G; Nilsson, P; Palmer, C N A; Rayner, N W; Renström, F; Ribel-Madsen, R; Robertson, N; Rolandsson, O; Rossing, P; Schwartz, T W; Slagboom, P E; Sterner, M; Tang, M; Tarnow, L; Tuomi, T; van't Riet, E; van Leeuwen, N; Varga, T V; Vestmar, M A; Walker, M; Wang, B; Wang, Y; Wu, H; Xi, F; Yengo, L; Yu, C; Zhang, X; Zhang, J; Zhang, Q; Zhang, W; Zheng, H; Zhou, Y; Altshuler, D; 't Hart, L M; Franks, P W; Balkau, B; Froguel, P; McCarthy, M I; Laakso, M; Groop, L; Christensen, C; Brandslund, I; Lauritzen, T; Witte, D R; Linneberg, A; Jørgensen, T; Hansen, T; Wang, J; Nielsen, R; Pedersen, O

2013-02-01

Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Can We Use Regression Modeling to Quantify Mean Annual Streamflow at a Global-Scale?

NASA Astrophysics Data System (ADS)

Barbarossa, V.; Huijbregts, M. A. J.; Hendriks, J. A.; Beusen, A.; Clavreul, J.; King, H.; Schipper, A.

2016-12-01

Quantifying mean annual flow of rivers (MAF) at ungauged sites is essential for a number of applications, including assessments of global water supply, ecosystem integrity and water footprints. MAF can be quantified with spatially explicit process-based models, which might be overly time-consuming and data-intensive for this purpose, or with empirical regression models that predict MAF based on climate and catchment characteristics. Yet, regression models have mostly been developed at a regional scale and the extent to which they can be extrapolated to other regions is not known. In this study, we developed a global-scale regression model for MAF using observations of discharge and catchment characteristics from 1,885 catchments worldwide, ranging from 2 to 106 km2 in size. In addition, we compared the performance of the regression model with the predictive ability of the spatially explicit global hydrological model PCR-GLOBWB [van Beek et al., 2011] by comparing results from both models to independent measurements. We obtained a regression model explaining 89% of the variance in MAF based on catchment area, mean annual precipitation and air temperature, average slope and elevation. The regression model performed better than PCR-GLOBWB for the prediction of MAF, as root-mean-square error values were lower (0.29 - 0.38 compared to 0.49 - 0.57) and the modified index of agreement was higher (0.80 - 0.83 compared to 0.72 - 0.75). Our regression model can be applied globally at any point of the river network, provided that the input parameters are within the range of values employed in the calibration of the model. The performance is reduced for water scarce regions and further research should focus on improving such an aspect for regression-based global hydrological models.

Effects of oxaliplatin and oleic acid Gc-protein-derived macrophage-activating factor on murine and human microglia.

PubMed

Branca, Jacopo J V; Morucci, Gabriele; Malentacchi, Francesca; Gelmini, Stefania; Ruggiero, Marco; Pacini, Stefania

2015-09-01

The biological properties and characteristics of microglia in rodents have been widely described, but little is known about these features in human microglia. Several murine microglial cell lines are used to investigate neurodegenerative and neuroinflammatory conditions; however, the extrapolation of the results to human conditions is frequently met with criticism because of the possibility of species-specific differences. This study compares the effects of oxaliplatin and of oleic acid Gc-protein-derived macrophage-activating factor (OA-GcMAF) on two microglial cell lines, murine BV-2 cells and human C13NJ cells. Cell viability, cAMP levels, microglial activation, and vascular endothelial growth factor (VEGF) expression were evaluated. Our data demonstrate that oxaliplatin induced a significant decrease in cell viability in BV-2 and in C13NJ cells and that this effect was not reversed with OA-GcMAF treatment. The signal transduction pathway involving cAMP/VEGF was activated after treatment with oxaliplatin and/or OA-GcMAF in both cell lines. OA-GcMAF induced a significant increase in microglia activation, as evidenced by the expression of the B7-2 protein, in BV-2 as well as in C13NJ cells that was not associated with a concomitant increase in cell number. Furthermore, the effects of oxaliplatin and OA-GcMAF on coculture morphology and apoptosis were evaluated. Oxaliplatin-induced cell damage and apoptosis were nearly completely reversed by OA-GcMAF treatment in both BV-2/SH-SY5Y and C13NJ/SH-SY5Y cocultures. Our data show that murine and human microglia share common signal transduction pathways and activation mechanisms, suggesting that the murine BV-2 cell line may represent an excellent model for studying human microglia. © 2015 Wiley Periodicals, Inc.

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

Workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, install the last engine on the S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor.

PubMed

Matsuura, Takashi; Uematsu, Takashi; Yamaoka, Minoru; Furusawa, Kiyofumi

2004-03-01

The aim of this study was to clarify the effects of alpha-N-acetylgalactosaminidase (alpha-NaGalase) produced by human salivary gland adenocarcinoma (SGA) cells on the bioactivity of macrophage-activating factor (GcMAF). High exo-alpha-NaGalase activity was detected in the SGA cell line HSG. HSG alpha-NaGalase had both exo- and endo-enzyme activities, cleaving the Gal-GalNAc and GalNAc residues linked to Thr/Ser but not releasing the [NeuAc2-6]GalNac residue. Furthermore, GcMAF enzymatically prepared from the Gc protein enhanced the superoxide-generation capacity and phagocytic activity of monocytes/macrophages. However, GcMAF treated with purified alpha-NaGalase did not exhibit these effects. Thus, HSG possesses the capacity to produce larger quantities of alpha-NaGalase, which inactivates GcMAF produced from Gc protein, resulting in reduced phagocytic activity and superoxide-generation capacity of monocytes/macrophages. The present data strongly suggest that HSG alpha-NaGalase acts as an immunodeficiency factor in cancer patients.

Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.

PubMed Central

Soncin, M.; Polo, L.; Reddi, E.; Jori, G.; Kenney, M. E.; Cheng, G.; Rodgers, M. A.

1995-01-01

Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and phototherapeutic efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The GePcs were i.v. injected at a dose of 0.35 mumol kg-1 body weight after incorporation into either Cremophor emulsions or small unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the delivery system and the chemical structure of the phthalocyanine were found to affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding liposome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced for those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc(hexyl)2 at 24 h after injection. Consistently, the Ge-Pc(hexyl)2, administered via Cremophor, showed the highest phototherapeutic activity towards MS-2 fibrosarcoma. PMID:7710936

Dehydration-induced endodormancy in crown buds of leafy spurge highlights involvement of MAF3- and RVE1-like homologs, and hormone signaling cross-talk.

PubMed

Doğramacı, Münevver; Horvath, David P; Anderson, James V

2014-11-01

Vegetative shoot growth from underground adventitious buds of leafy spurge is critical for survival of this invasive perennial weed after episodes of severe abiotic stress. To determine the impact that dehydration-stress has on molecular mechanisms associated with vegetative reproduction of leafy spurge, greenhouse plants were exposed to mild- (3-day), intermediate- (7-day), severe- (14-day) and extended- (21-day) dehydration treatments. Aerial tissues of treated plants were then decapitated and soil was rehydrated to determine the growth potential of underground adventitious buds. Compared to well-watered plants, mild-dehydration accelerated new vegetative shoot growth, whereas intermediate- through extended-dehydration treatments both delayed and reduced shoot growth. Results of vegetative regrowth further confirmed that 14 days of dehydration induced a full-state of endodormancy in crown buds, which was correlated with a significant (P < 0.05) change in abundance of 2,124 transcripts. Sub-network enrichment analyses of transcriptome data obtained from the various levels of dehydration treatment also identified central hubs of over-represented genes involved in processes such as hormone signaling (i.e., ABA, auxin, ethylene, GA, and JA), response to abiotic stress (DREB1A/2A, RD22) and light (PIF3), phosphorylation (MPK4/6), circadian regulation (CRY2, PHYA), and flowering (AGL20, AP2, FLC). Further, results from this and previous studies highlight homologs most similar to Arabidopsis HY5, MAF3, RVE1 and RD22 as potential molecular markers for endodormancy in crown buds of leafy spurge. Early response to mild dehydration also highlighted involvement of upstream ethylene and JA-signaling, whereas severe dehydration impacted ABA-signaling. The identification of conserved ABRE- and MYC-consensus, cis-acting elements in the promoter of leafy spurge genomic clones similar to Arabidopsis RVE1 (AT5G17300) implicates a potential role for ABA-signaling in its dehydration

SU-E-CAMPUS-I-04: Automatic Skin-Dose Mapping for An Angiographic System with a Region-Of-Interest, High-Resolution Detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vijayan, S; Rana, V; Setlur Nagesh, S

2014-06-15

Purpose: Our real-time skin dose tracking system (DTS) has been upgraded to monitor dose for the micro-angiographic fluoroscope (MAF), a high-resolution, small field-of-view x-ray detector. Methods: The MAF has been mounted on a changer on a clinical C-Arm gantry so it can be used interchangeably with the standard flat-panel detector (FPD) during neuro-interventional procedures when high resolution is needed in a region-of-interest. To monitor patient skin dose when using the MAF, our DTS has been modified to automatically account for the change in scatter for the very small MAF FOV and to provide separated dose distributions for each detector. Themore » DTS is able to provide a color-coded mapping of the cumulative skin dose on a 3D graphic model of the patient. To determine the correct entrance skin exposure to be applied by the DTS, a correction factor was determined by measuring the exposure at the entrance surface of a skull phantom with an ionization chamber as a function of entrance beam size for various beam filters and kVps. Entrance exposure measurements included primary radiation, patient backscatter and table forward scatter. To allow separation of the dose from each detector, a parameter log is kept that allows a replay of the procedure exposure events and recalculation of the dose components.The graphic display can then be constructed showing the dose distribution from the MAF and FPD separately or together. Results: The DTS is able to provide separate displays of dose for the MAF and FPD with field-size specific scatter corrections. These measured corrections change from about 49% down to 10% when changing from the FPD to the MAF. Conclusion: The upgraded DTS allows identification of the patient skin dose delivered when using each detector in order to achieve improved dose management as well as to facilitate peak skin-dose reduction through dose spreading. Research supported in part by Toshiba Medical Systems Corporation and NIH Grants R43FD0158401

Validating Facial Aesthetic Surgery Results with the FACE-Q.

PubMed

Kappos, Elisabeth A; Temp, Mathias; Schaefer, Dirk J; Haug, Martin; Kalbermatten, Daniel F; Toth, Bryant A

2017-04-01

In aesthetic clinical practice, surgical outcome is best measured by patient satisfaction and quality of life. For many years, there has been a lack of validated questionnaires. Recently, the FACE-Q was introduced, and the authors present the largest series of face-lift patients evaluated by the FACE-Q with the longest follow-up to date. Two hundred consecutive patients were identified who underwent high-superficial musculoaponeurotic system face lifts, with or without additional facial rejuvenation procedures, between January of 2005 and January of 2015. Patients were sent eight FACE-Q scales and were asked to answer questions with regard to their satisfaction. Rank analysis of covariance was used to compare different subgroups. The response rate was 38 percent. Combination of face lift with other procedures resulted in higher satisfaction than face lift alone (p < 0.05). Patients who underwent lipofilling as part of their face lift showed higher satisfaction than patients without lipofilling in three subscales (p < 0.05). Facial rejuvenation surgery, combining a high-superficial musculoaponeurotic system face lift with lipofilling and/or other facial rejuvenation procedures, resulted in a high level of patient satisfaction. The authors recommend the implementation of the FACE-Q by physicians involved in aesthetic facial surgery, to validate their clinical outcomes from a patient's perspective.

Optimization of the diffusive gradients in thin films (DGT) method for simultaneous assay of potassium and plant-available phosphorus in soils.

PubMed

Zhang, Yulin; Mason, Sean; McNeill, Ann; McLaughlin, Michael J

2013-09-15

Potassium (K) and phosphorus (P) are two important macronutrients for crops, and are usually applied to soils as granular fertilizer before seeding. Therefore, accurate soil tests prior to planting to predict crop response to fertilizers are important in optimizing crop yields. Traditional methods used for testing both available K and P in soils, which are based on chemical extraction procedures, are to be soil-type dependent, and the predictive relationships across a broad range of soils are generally poor. The diffusive gradients in thin films (DGT) technique, based on diffusion theory, is extensively used to measure the diffusive supply of trace elements, metals and some nutrients in soils and water. When DGT is used to assess plant-available P in soils, a good relationship is found between crop response to P fertilizer and concentrations of P in soil measured by DGT, and therefore the DGT method provides a more precise recommendation of P fertilizer requirements. Adaptation of the DGT method to measure plant-available K in soils has already been attempted [1], but limitations were reported due to the non-uniform size of the resin gel, decreased K binding rate of the gel at long deployment times and a limited ability to measure a wide range of K concentrations. To eliminate these problems, a new resin gel has been developed by combining Amberlite and ferrihydrite. This mixed Amberlite and ferrihydrite (MAF) gel has improved properties in terms of handling and even distribution of Amberlite in the gel. The elution efficiencies of the MAF gel for K and P were 90% and 96%, respectively. The diffusion coefficient of K through the diffusive gel was 1.30 × 10(-5)cm(2)s(-1) at 22 ± 1°C and was stable through time. Since ferrihydrite is already used in DGT P testing, the ability of the MAF gel to assess available P simultaneously was also assessed. The MAF gel performed the same as the traditional ferrihydrite gel for available P assessment in a wide variety of

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats.

PubMed

Burade, Vinod; Bhowmick, Subhas; Maiti, Kuntal; Zalawadia, Rishit; Jain, Deepak; Rajamannar, Thennati

2017-05-01

The liposomal formulation of doxorubicin [doxorubicin (DXR) hydrochloride (HCl) liposome injection, Caelyx ® ] alters the tissue distribution of DXR as compared with nonliposomal DXR, resulting in an improved benefit-risk profile. We conducted studies in murine models to compare the plasma and tissue distribution of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceuticals Industries Limited (SPIL DXR HCl liposome injection) with Caelyx ® . The plasma and tissue distributions of the SPIL and reference DXR HCl liposome injections were compared in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Different batches and different lots of the same batch of the reference product were also compared with each other. The SPIL and reference DXR HCl liposome injections exhibited generally comparable plasma and tissue distribution profiles in both models. While minor differences were observed between the two products in some tissues, different batches and lots of the reference product also showed some differences in the distribution of various analytes in some tissues. The ratios of estimated free to encapsulated DXR for plasma and tissue were generally comparable between the SPIL and reference DXR HCl liposome injections in both models, indicating similar extents of absorption into the tissues and similar rates of drug release from liposomes. The plasma and tissue distribution profiles of the SPIL and reference DXR HCl liposome injections were shown to be generally comparable. Inconsistencies between the products observed in some tissues were thought to be due to biological variation.

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

Three S-IB stages near completion at the NASA's Michoud Assembly Facility (MAF) near New Orleans, Louisiana, in November 1967. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at MAF, the 90,000-pound booster utilized eight H-1 engines and each produced 200,000 pounds of thrust for the Saturn IB launch vehicle's first stage.

Saturn Apollo Program

NASA Image and Video Library

1968-01-01

The Saturn 1B S-IB (first) stage being prepared for shipment at Michoud Assembly Facility (MAF), near New Orleans, Louisiana. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at MAF, the S-IB stage utilized the eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

PubMed Central

Soucie, Erinn L.; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Gregory; VanHille, Laurent; Beniazza, Meryam; Favret, Jeremy; Berruyer, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, J.-C.; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H.

2016-01-01

Differentiated macrophages can self-renew in tissues and expand long-term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. Single cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. PMID:26797145

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

PubMed Central

Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

1998-01-01

To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

Power considerations for λ inflation factor in meta-analyses of genome-wide association studies.

PubMed

Georgiopoulos, Georgios; Evangelou, Evangelos

2016-05-19

The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor (λ) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0·001 to 0·5 and λ was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real λ values) and (ii) selected scenario from simulation parameter modification. Adjustment for λ was considered under single correction (within study corrected standard errors) and double correction (additional λ corrected summary estimate). MAF was a pivotal determinant of observed power. In random λ scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF 1·2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.

Mango seed uses: thermal behaviour of mango seed almond fat and its mixtures with cocoa butter.

PubMed

Solís-Fuentes, J A; Durán-de-Bazúa, M C

2004-03-01

This paper deals with the physicochemical characterization, including thermal behaviour, by differential scanning calorimetry of mango seed almond fat (MAF), alone and in mixtures with cocoa butter (CB). Results showed that mango almond seeds contain about 5.28-11.26% (dw) of fat. The refraction index is 1.466, the saponification index 189.0 and the iodine index 41.76. Fatty acids found in MAF are oleic, stearic, and palmitic acids (40.81%, 39.07% and 9.29% (w/w), respectively) as well as smaller amounts of linoleic, with arachidic, behenic, lignoceric, and linolenic acids, among others. Calorimetric analysis showed that MAF crystallizes between 14.6 and -24.27 degrees C with a DeltaHc of 56.06 J/g and melts between -17.1 and 53.8 degrees C, with fusion maxima at 18.54 degrees C and 40.0 degrees C for the alpha and beta polymorphic forms. Their fusion enthalpies are 70.12 and 115.7 J/g. The MAF solids content profile is very similar to that of CB, both in stabilized and non-stabilized samples. The mixing compatibility was analyzed using isosolids curves of mixtures of different compositions.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

Workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, hoist the thrust structure assembly for the Saturn IB S-IB (first) stage. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

PubMed

Sumiya, Yu; Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2015-08-01

Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells.

PubMed

Soucie, Erinn L; Weng, Ziming; Geirsdóttir, Laufey; Molawi, Kaaweh; Maurizio, Julien; Fenouil, Romain; Mossadegh-Keller, Noushine; Gimenez, Gregory; VanHille, Laurent; Beniazza, Meryam; Favret, Jeremy; Berruyer, Carole; Perrin, Pierre; Hacohen, Nir; Andrau, J-C; Ferrier, Pierre; Dubreuil, Patrice; Sidow, Arend; Sieweke, Michael H

2016-02-12

Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells. Copyright © 2016, American Association for the Advancement of Science.

Effect of variable soil texture, metal saturation of soil organic matter (SOM) and tree species composition on spatial distribution of SOM in forest soils in Poland.

PubMed

Gruba, Piotr; Socha, Jarosław; Błońska, Ewa; Lasota, Jarosław

2015-07-15

In this study we investigated the effect of fine (ϕ<0.05mm) fraction, i.e., silt+clay (FF) content in soils, site moisture, metal (Al and Fe) of soil organic matter (SOM) and forest species composition on the spatial distribution of carbon (C) pools in forest soils at the landscape scale. We established 275 plots in regular 200×200m grid in a forested area of 14.4km(2). Fieldwork included soil sampling of the organic horizon, mineral topsoil and subsoil down to 40cm deep. We analysed the vertical and horizontal distribution of soil organic carbon (SOC) stocks, as well as the quantity of physically separated fractions including the free light (fLF), occluded light (oLF) and mineral associated fractions (MAF) in the mineral topsoil (A, AE) horizons. Distribution of C in soils was predominantly affected by the variation in the FF content. In soils richer in the FF more SOC was accumulated in mineral horizons and less in the organic horizons. Accumulation of SOC in mineral soil was also positively affected by the degree of saturation of SOM with Al and Fe. The increasing share of beech influenced the distribution of C stock in soil profiles by reducing the depth of O horizon and increasing C stored in mineral soil. The content of FF was positively correlated with the content of C in MAF and fLF fractions. The content of oLF and MAF fractions was also positively influenced by a higher degree of metal saturation, particularly Al. Our results confirmed that Al plays an important role in the stabilization of SOM inside aggregates (CoLF) and as in CMAF fractions. We also found a significant, positive effect of beech on the CfLF and fir on the CoLF content. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular Determinants of Antiestrogen and Drug Sensitivity in Breast Carcinoma Cells

DTIC Science & Technology

1997-08-01

W.S. human HT1080 fibrosarcoma cells (a gift of Pear, personal communication). G.R. Stark), susceptible to ecotropic retrovirus In several...transfection with equal amounts of plasmid pOPRSVIluc (generated by replacing CAT of pORRSVICAT with luc) which expresses luc from R02 promoter, and control...retroviral transduction into (Fig. 1). During transient co-transfection of NIH 3T3 human HT1080 fibrosarcoma or mouse NIH 3T3 cell cells with a laac expressing

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 4, Volume 3, Appendix 11: Final Pathology Report

DTIC Science & Technology

1984-04-01

bladder 1 muscle, s k e l e t a l 5 bone marrow smear --- 3 nasal t u rb ina tes *ti ~ s u e masses ,- and any o the r t i ssues w i t h...Lymphoma, lymphocytic type .__ - __ __ ___ .____. . _ - --- Fibrosarcoma , me ta s t a t i c - __ .._._- _ __._ - - .- Granulosa-cell Carcinoma... Fibrosarcoma , m e t a s t a t i c . -- RENAL LYMPH NODE -- E ’ L - --.I- t Malignant Lymphoma, mixed type Malignant

Radiation induction of cancer of the skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fry, R.J.M.; Storer, J.B.; Burns, F.J.

1985-01-01

The induction of epidermal tumors was studied using exposures to 25 kV x-rays with or without subsequent exposures to 12-0-tetradeconyl phorbol-13 acetate (TPA) or ultraviolet radiation (uvr) 280-400 nm. Fractionation regimens and total exposure up to 4000R produced no squamous cell carcinomas. When these regimes were followed by TPA an incidence of about 80% was obtained, and incidence of 60% when uvr exposures followed the x-irradiation. A dose-dependent increase in fibrosarcomas was found when x-irradiation was followed by 24 weeks of topical treatment with TPA. These results support the contention that uvr can enhance the expression of cells initiated bymore » x-rays. The experimental evidence is compared with the data from the tinea capitis patients treated with x-rays. In C3HF/He male mice exposed to 50, 100, 150 and 200 rads /sup 137/Cs gamma rays the induction rate for fibrosarcomas was 2.9 x 10/sup -4/ per cGy/per mouse. This result compares with 2.5 x 10/sup -6/ transformations per surviving cell per cGy with 10T1/2 cells that are fibroblasts derived from C3H mice. 16 refs., 1 fig., 1 tab.« less

MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement.

PubMed

Doyle, Leona A; Wang, Wei-Lien; Dal Cin, Paola; Lopez-Terrada, Dolores; Mertens, Fredrik; Lazar, Alexander J F; Fletcher, Christopher D M; Hornick, Jason L

2012-10-01

Sclerosing epithelioid fibrosarcoma (SEF) is a rare aggressive fibroblastic neoplasm composed of cords of epithelioid cells embedded in a dense collagenous stroma. The reported immunophenotype of SEF is nonspecific. Some SEF cases show morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS), suggesting a relationship between these tumor types. MUC4 has recently been identified as a sensitive and specific marker for LGFMS; MUC4 expression was also observed in 2 tumors with hybrid features of SEF and LGFMS. We investigated MUC4 expression in SEF and other epithelioid soft tissue tumors to determine (1) the potential diagnostic utility of MUC4 for SEF and (2) the association between MUC4 expression and FUS rearrangement in SEF. Whole sections of 180 tumors were evaluated: 41 cases of SEF (including 29 "pure" SEF and 12 hybrid LGFMS-SEF), 20 epithelioid sarcomas, 11 clear cell sarcomas, 11 metastatic melanomas, 10 perivascular epithelioid cell tumors, 10 alveolar soft part sarcomas, 10 epithelioid angiosarcomas, 10 epithelioid hemangioendotheliomas, 10 epithelioid gastrointestinal stromal tumors, 10 myoepithelial carcinomas, 17 ossifying fibromyxoid tumors, 10 leiomyosarcomas, and 10 biphasic synovial sarcomas. Immunohistochemical analysis was performed after antigen retrieval using a mouse anti-MUC4 monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed on 33 SEF cases using FUS break-apart probes. A subset of cases was also evaluated for EWSR1 and CREB3L2/L1 rearrangements by FISH. Strong diffuse cytoplasmic staining for MUC4 was observed in 32 of 41 (78%) cases of SEF, including all 12 hybrid tumors. FUS rearrangement was detected in 8 of 21 (38%) MUC4-positive cases of SEF with successful FISH studies. The prevalence of FUS rearrangement was similar in hybrid LGFMS-SEF (2 of 6; 33%) and SEF without an LGFMS component (6 of 15; 40%). FUS rearrangement was not detected in any cases of MUC4-negative SEF. Two hybrid tumors had

Radiation-induced antrochoanal fibrosarcoma.

PubMed

Liddington, M I; Harrison, R F; Booth, A P; Das Gupta, A R

1992-06-01

Therapeutic radiation for malignant conditions is known to cause sarcomatous change in an irradiated field after a latent period; equally this change may occur following radiotherapy to benign conditions which may result in a more difficult management problem later. Radiotherapy to benign conditions should be reserved for use after failure of conventional surgery or other interventional techniques.

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel.

PubMed

Mitt, Mario; Kals, Mart; Pärn, Kalle; Gabriel, Stacey B; Lander, Eric S; Palotie, Aarno; Ripatti, Samuli; Morris, Andrew P; Metspalu, Andres; Esko, Tõnu; Mägi, Reedik; Palta, Priit

2017-06-01

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF)≥5% and low-frequency variants (0.5≤MAF<5%) across diverse populations, but the imputation of rare variation (MAF<0.5%) is still rather limited. In the current study, we evaluate imputation accuracy achieved with reference panels from diverse populations with a population-specific high-coverage (30 ×) whole-genome sequencing (WGS) based reference panel, comprising of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian-specific panel contains fewer haplotypes and variants, the imputation confidence and accuracy of imputed low-frequency and rare variants was significantly higher. The results indicate the utility of population-specific reference panels for human genetic studies.

Multimodal, multiphoton microscopy and image correlation analysis for characterizing corneal thermal damage

NASA Astrophysics Data System (ADS)

Lo, Wen; Chang, Yu-Lin; Liu, Jia-Shiu; Hseuh, Chiu-Mei; Hovhannisyan, Vladimir; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

2009-09-01

We used the combination of multiphoton autofluorescence (MAF), forward second-harmonic generation (FWSHG), and backward second-harmonic generation (BWSHG) imaging for the qualitative and quantitative characterization of thermal damage of ex vivo bovine cornea. We attempt to characterize the structural alterations by qualitative MAF, FWSHG, and BWSHG imaging in the temperature range of 37 to 90°C. In addition to measuring the absolute changes in the three types of signals at the stromal surface, we also performed image correlation analysis between FWSHG and BWSHG and demonstrate that with increasing thermal damage, image correlation between FWSHG and BWSHG significantly increases. Our results show that while MAF and BWSHG intensities may be used as preliminary indicators of the extent of corneal thermal damage, the most sensitive measures are provided by the decay in FWSHG intensity and the convergence of FWSHG and BWSHG images.

Psychometric evaluation of the Multidimensional Assessment of Fatigue scale for use with pregnant and postpartum women.

PubMed

Fairbrother, Nichole; Hutton, Eileen K; Stoll, Kathrin; Hall, Wendy; Kluka, Sandy

2008-06-01

Although fatigue is a common experience for pregnant women and new mothers, few measures of fatigue have been validated for use with this population. To address this gap, the authors assessed psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale, which was used in 2 independent samples of pregnant women. Results indicated that the psychometric properties of the scale were very similar across samples and time points. The scale possesses a high level of internal consistency, has good convergent validity with measures of sleep quality and depression, and discriminates well from a measure of social support. Contrary to previous evaluations of the MAF, data strongly suggest that the scale represents a unidimensional construct best represented by a single factor. Results indicate that the MAF is a useful measure of fatigue among pregnant and postpartum women.

Gender Integration in the USAF Fighter Community: 25 Years of Progress and Persistent Challenges

DTIC Science & Technology

2017-04-25

experience. This work builds on the research of two AF Fellows who studied female aviators in the Mobility Air Force (MAF) in 2015 to address subtle...distilling the 25- year period under study . Prior to determining instructional fixes, great instructors listen to their students and other members...were a number of non-member Company Grade Officers (CGOs), to understand their experiences and thoughts on retention.18 As in the MAF studies , but to a

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In one of the initial assembly steps for the Saturn IB launch vehicle's S-IB (first) stage, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, position the thrust structure. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In one of the initial assembly steps for the Saturn IB launch vehicle's S-IB (first) stage, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, complete the thrust structure. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study

PubMed Central

Piskorz, Anna M.; Biggs, Heather; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen; Gounaris, Ioannis; Earl, Helena M.; Rosenfeld, Nitzan; Brenton, James D.

2016-01-01

Background Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). Methods and Findings We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%–22%) compared to 0.7% (IQR 0.3%–2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to

Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

PubMed

Parkinson, Christine A; Gale, Davina; Piskorz, Anna M; Biggs, Heather; Hodgkin, Charlotte; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen; Gounaris, Ioannis; Jimenez-Linan, Mercedes; Earl, Helena M; Qian, Wendi; Rosenfeld, Nitzan; Brenton, James D

2016-12-01

Circulating tumour DNA (ctDNA) carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC). We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP). We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF) was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22%) compared to 0.7% (IQR 0.3%-2.0%) for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p < 0.001), and this correlation improved when patients with ascites were excluded (r = 0.82). The ratio of TP53MAF to volume of disease was higher in relapsed patients (0.04% per cm3) than in untreated patients (0.0008% per cm3, p = 0.004). In nearly all relapsed patients with disease volume > 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ct

Repair of a facial defect with an interpolation skin flap in a cat.

PubMed

Allen, S W; Miller, M A; Haas, K M

1997-05-01

A 9-year-old domestic shorthair cat was referred for removal of a rostrally located fibrosarcoma on the face, which had previously recurred twice following excision. A wide excision was performed, using a neodymium:yttrium-aluminumgarnet (Nd:YAG) laser, resulting in a facial defect that could not be closed by primary suture. An interpolation skin flap was elevated, using skin from the side of the cat's face, and sutured in place over the defect. Recurrence of the tumor at the medial canthus of the left eye, which was observed 4 months after surgery, was treated by laser excision and cryotherapy. Other recurrences of the fibrosarcoma were not noticed for 2.5 years after referral, at which time the cat was euthanatized for other reasons. Necropsy revealed that the fibrosarcoma had not recurred. In this cat, an interpolation skin flap was useful in repairing a large rostral facial defect. Care should be taken when elevating this flap to preserve the palpebral nerve.

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-12-01

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

MAF Resource Reel August 2016

NASA Image and Video Library

2016-08-01

Edited b-roll video of NASA's Michoud Assembly Facility, which is managed by the Marshall Space Flight Center in Huntsville, Alabama. This B-roll shows various projects including manufacturing of the Space Launch System core stage and the Orion spacecraft pressure vessel. It includes interior and exterior views of the facility. For more information and more detailed footage, please contact the center's Public & Employee Communications Office. PAO Name:Tracy McMahan Phone Number:256-544-0034 Email Address: tracy.mcmahan@nasa.gov

The Michoud Assembly Facility (MAF)

NASA Technical Reports Server (NTRS)

2000-01-01

NASA's Michoud Assembly Facility, located in eastern New Orleans, Louisiana, is an 832 acre site that is a government-owned, contractor-operated component of the George C. Marshall Space Flight Center (MSFC). The facility was acquired by NASA in 1961 at the recommendation of Dr. Wernher von Braun and his rocket team in Huntsville Alabama. The cavernous plant served as the assembly facility for the Saturn launch vehicles and most recently the external tank (ET) used for the Space Shuttle Program. The facility features one of the world's biggest manufacturing plants with 43 acres under one roof and a port with deep-water access for the transportation of large space structures. When completed, space hardware is towed on a barge across the Gulf of Mexico, around Florida and up to Kennedy Space Center. The original tract of land was part of a 34,500 acre French Royal land grant to local merchant, Gilbert Antoine de St. Maxent in 1763. Later, the land was acquired by French transplant Antoine Michoud, the son of Napoleon's Administrator of Domains, who moved to the city in 1827. Michoud operated a sugar cane plantation and refinery on the site until his death in 1863. His heirs continued operating the refinery and kept the original St. Maxent estate intact into the 20th century. Visible on the right, is one of two brick smokestacks from the original refinery that still stand before the Michoud facility today.

The Michoud Assembly Facility (MAF)

NASA Technical Reports Server (NTRS)

2000-01-01

NASA's Michoud Assembly Facility, located in eastern New Orleans, Louisiana, is an 832 acre site that is a government-owned, contractor-operated component of the George C. Marshall Space Flight Center (MSFC). The facility was acquired by NASA in 1961 at the recommendation of Dr. Wernher von Braun and his rocket team in Huntsville Alabama. The cavernous plant served as the assembly facility for the Saturn launch vehicles and most recently the external tank (ET) used for the Space Shuttle Program. The facility features one of the world's biggest manufacturing plants with 43 acres under one roof and a port with deep-water access for the transportation of large space structures. When completed, space hardware is towed on a barge across the Gulf of Mexico, around Florida and up to Kennedy Space Center. The original tract of land was part of a 34,500 acre French Royal land grant to local merchant, Gilbert Antoine de St. Maxent in 1763. Later, the land was acquired by French transplant Antoine Michoud, the son of Napoleon's Administrator of Domains, who moved to the city in 1827. Michoud operated a sugar cane plantation and refinery on the site until his death in 1863. His heirs continued operating the refinery and kept the original St. Maxent estate intact into the 20th century. Two brick smokestacks from the original refinery still stand before the Michoud facility today.

75 FR 47709 - Amendment of VOR Federal Airways V-8, V-14, V-38, V-47, V-279, and V-422 in the Vicinity of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-09

...-0709; Airspace Docket No. 09-AGL-28] RIN 2120-AA66 Amendment of VOR Federal Airways V-8, V-14, V-38, V-47, V-279, and V-422 in the Vicinity of Findlay, OH AGENCY: Federal Aviation Administration (FAA... Range (VOR) Federal Airways V-8, V-14, V-38, V-47, V- 279, and V-422 in the vicinity of Findlay, OH. The...

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

ClinicalTrials.gov

2018-05-30

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Melanoma; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms; Fibrosarcoma; Infantile Fibrosarcoma; Congenital Mesoblastic Nephroma; Central Nervous System Neoplasms

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In one of the initial assembly steps for the Saturn IB launch vehicle's S-IB (first) stage, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, complete the lower shroud assembly. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized the eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the clustering procedure, an initial assembly step for the Saturn IB launch vehicle's S-IB (first) stage, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, position the central liquid-oxygen tank. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel

PubMed Central

Mitt, Mario; Kals, Mart; Pärn, Kalle; Gabriel, Stacey B; Lander, Eric S; Palotie, Aarno; Ripatti, Samuli; Morris, Andrew P; Metspalu, Andres; Esko, Tõnu; Mägi, Reedik; Palta, Priit

2017-01-01

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF)≥5% and low-frequency variants (0.5≤MAF<5%) across diverse populations, but the imputation of rare variation (MAF<0.5%) is still rather limited. In the current study, we evaluate imputation accuracy achieved with reference panels from diverse populations with a population-specific high-coverage (30 ×) whole-genome sequencing (WGS) based reference panel, comprising of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian-specific panel contains fewer haplotypes and variants, the imputation confidence and accuracy of imputed low-frequency and rare variants was significantly higher. The results indicate the utility of population-specific reference panels for human genetic studies. PMID:28401899

Measuring awareness of financial skills: reliability and validity of a new measure.

PubMed

Cramer, K; Tuokko, H A; Mateer, C A; Hultsch, D F

2004-03-01

This paper examines the psychometric properties of a three-part (participant, informant, and performance) Measure for assessing Awareness of Financial Skills (MAFS). The MAFS was administered to 10 seniors with dementia and 25 well-functioning seniors, and their informants. Measures of cognitive functioning, social desirability, neuroticism, and perceived control were administered to each participant to allow for an assessment of validity. Internal consistency estimates for the participant and informant questionnaires were found to be 0.92 and 0.97, respectively. Convergent validity analysis indicated that performance on this measure was related to level of cognitive functioning, with higher level of unawareness associated with decreased cognitive ability. Discriminant validity analysis showed that performance on this measure was not related to social desirability or neuroticism. This study provides evidence that the MAFS is a reliable and valid tool for assessing awareness of financial skills in older adults.

MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies.

PubMed

Honoré, Paul; Granjeaud, Samuel; Tagett, Rebecca; Deraco, Stéphane; Beaudoing, Emmanuel; Rougemont, Jacques; Debono, Stéphane; Hingamp, Pascal

2006-09-20

High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option.GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and industry service providers alike.

MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies

PubMed Central

Honoré, Paul; Granjeaud, Samuel; Tagett, Rebecca; Deraco, Stéphane; Beaudoing, Emmanuel; Rougemont, Jacques; Debono, Stéphane; Hingamp, Pascal

2006-01-01

Background High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option. GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported. Results MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF. Conclusion MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and

Genetic association with low concentrations of high density lipoprotein-cholesterol in a pediatric population of the Middle East and North Africa: the CASPIAN-III study.

PubMed

Kelishadi, Roya; Haghjooy Javanmard, Shaghayegh; Tajadini, Mohammad Hasan; Mansourian, Marjan; Motlagh, Mohammad Esmaeil; Ardalan, Gelayol; Ban, Matthew

2014-11-01

Depressed high-density lipoprotein cholesterol (HDL-C) is prevalent the Middle East and North Africa. Some studies have documented associations between HDL-C and several single nucleotide polymorphisms (SNPs) in candidate gene polymorphisms. We investigated the associations between SNP genotypes and HDL-C levels in Iranian students, aged 10-18 years. Genotyping was performed in 750 randomly selected participants among those with low HDL-C levels (below 5th percentile), intermediate HDL-C levels (5-95th) and high HDL-C levels (above the 95th percentile). Minor allele frequencies (MAFs) of the SNPs of interest were compared between the three HDL-C groups. The vast majority of pairwise comparisons of MAFs between HDL-C groups were significant. Pairwise comparisons between low and high HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for APOC3 rs5128. Pairwise comparisons between low and intermediate HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for APOC3 rs5128 and APOA1 rs2893157. Pairwise comparisons between intermediate and high HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for ABCA1 APOC3 rs5128 and APOA1 rs2893157. After adjustment for confounding factors, including age, sex, body mass index, low physical activity, consumption of saturated fats, and socioeconomic status, ABCA1 r1587K and CETP A373P significantly increased the risk of depressed HDL-C, and CETP Taq1 had a protective role. This study replicated several associations between HDL-C levels and candidate gene SNPs from genome-wide associations with HDL-C in Iranians from the pediatric age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

One Size Doesn’t Fit All: Measuring Individual Privacy in Aggregate Genomic Data

PubMed Central

Simmons, Sean; Berger, Bonnie

2017-01-01

Even in the aggregate, genomic data can reveal sensitive information about individuals. We present a new model-based measure, PrivMAF, that provides provable privacy guarantees for aggregate data (namely minor allele frequencies) obtained from genomic studies. Unlike many previous measures that have been designed to measure the total privacy lost by all participants in a study, PrivMAF gives an individual privacy measure for each participant in the study, not just an average measure. These individual measures can then be combined to measure the worst case privacy loss in the study. Our measure also allows us to quantify the privacy gains achieved by perturbing the data, either by adding noise or binning. Our findings demonstrate that both perturbation approaches offer significant privacy gains. Moreover, we see that these privacy gains can be achieved while minimizing perturbation (and thus maximizing the utility) relative to stricter notions of privacy, such as differential privacy. We test PrivMAF using genotype data from the Wellcome Trust Case Control Consortium, providing a more nuanced understanding of the privacy risks involved in an actual genome-wide association studies. Interestingly, our analysis demonstrates that the privacy implications of releasing MAFs from a study can differ greatly from individual to individual. An implementation of our method is available at http://privmaf.csail.mit.edu. PMID:29202050

Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages.

PubMed Central

Homma, Y; Hashimoto, T; Nagai, Y; Takenawa, T

1985-01-01

Alterations of phospholipid and arachidonic acid metabolism were studied by treatment of guinea-pig peritoneal-exudate macrophages with chemotactic peptide, formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) and macrophage activation factor (MAF). The chemotactic peptide caused a rapid rearrangement in inositol phospholipids, including a breakdown of polyphosphoinositides within 30s, followed by a resultant formation of phosphatidylinositol (PI), diacylglycerol, phosphatidic acid and non-esterified arachidonic acid within 5 min. In addition to these sequential alterations, arachidonic acid was released mainly from PI. On the other hand, MAF induced a slow liberation of arachidonic acid, mainly from phosphatidylethanolamine (PE) and phosphatidylcholine (PC) by phospholipase A2 after the incubation period of 30 min, but not any rapid changes in phospholipids. Treatment of macrophages for 15 min with fMet-Leu-Phe produced the leukotrienes (LTs) B4, C4 and D4, prostaglandins (PG) E2 and F2 alpha and thromboxane (TX) B2. In contrast, MAF could not stimulate the production of arachidonic acid metabolites during the incubation period of 15 min, but could enhance that of PGE2, PGF2 alpha, TXB2 and hydroxyeicosatetraenoic acids at 6 h. However, the stimulated formation of LTs was not detected at any time. These results indicate that the effects of fMet-Leu-Phe on both phospholipid and arachidonic acid metabolism are very different from those mediated by MAF. PMID:3931627

Cajanus cajan Linn. (Leguminosae) prevents alcohol-induced rat liver damage and augments cytoprotective function.

PubMed

Kundu, Rakesh; Dasgupta, Suman; Biswas, Anindita; Bhattacharya, Anirban; Pal, Bikas C; Bandyopadhyay, Debashis; Bhattacharya, Shelley; Bhattacharya, Samir

2008-08-13

Cajanus cajan Linn. (Leguminosae) is a nontoxic edible herb, widely used in Indian folk medicine for the prevention of various liver disorders. In the present study we have demonstrated that methanol-aqueous fraction (MAF2) of Cajanus cajan leaf extract could prevent the chronically treated alcohol induced rat liver damage. Chronic doses of alcohol (3.7 g/ kg) orally administered to rats for 28 days and liver function marker enzymes such as GPT, GOT, ALP and anti-oxidant enzyme activities were determined. Effect of MAF2 at a dose of 50mg/kg body weight on alcohol treated rats was noted. Alcohol effected significant increase in liver marker enzyme activities and reduced the activities of anti-oxidant enzymes. Co-administration of MAF2 reversed the liver damage due to alcohol; it decreased the activities of liver marker enzymes and augmented antioxidant enzyme activities. We also demonstrate significant decrease of the phase II detoxifying enzyme, UDP-glucuronosyl transferase (UGT) activity along with a three- and two-fold decrease of UGT2B gene and protein expression respectively. MAF2 co-administration normalized UGT activity and revived the expression of UGT2B with a concomitant expression and nuclear translocation of Nrf2, a transcription factor that regulates the expression of many cytoprotective genes. Cajanus cajan extract therefore shows a promise in therapeutic use in alcohol induced liver dysfunction.

V&V framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hills, Richard G.; Maniaci, David Charles; Naughton, Jonathan W.

2015-09-01

A Verification and Validation (V&V) framework is presented for the development and execution of coordinated modeling and experimental program s to assess the predictive capability of computational models of complex systems through focused, well structured, and formal processes.The elements of the framework are based on established V&V methodology developed by various organizations including the Department of Energy, National Aeronautics and Space Administration, the American Institute of Aeronautics and Astronautics, and the American Society of Mechanical Engineers. Four main topics are addressed: 1) Program planning based on expert elicitation of the modeling physics requirements, 2) experimental design for model assessment, 3)more » uncertainty quantification for experimental observations and computational model simulations, and 4) assessment of the model predictive capability. The audience for this document includes program planners, modelers, experimentalist, V &V specialist, and customers of the modeling results.« less

Saturn Apollo Program

NASA Image and Video Library

1965-01-01

In one of the initial assembly steps for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, position a "Spider Beam" to the central liquid-oxygen tank of the S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

This photograph is a view of the Saturn V S-IC-5 (first) flight stage being hoisted into the S-IC-B1 test stand at the Mississippi Test Facility (MTF), Bay St. Louis, Mississippi. Begirning operations in 1966, the MTF has two test stands, a dual-position structure for running the S-IC stage at full throttle, and two separate stands for the S-II (Saturn V third) stage. It became the focus of the static test firing program. The completed S-IC stage was shipped from Michoud Assembly Facility (MAF) to the MTF. The stage was then installed into the 124-meter-high test stand for static firing tests before shipment to the Kennedy Space Center for final assembly of the Saturn V vehicle. The MTF was renamed to the National Space Technology Laboratory (NSTL) in 1974 and later to the Stennis Space Center (SSC) in May 1988.

Monitoring the process of pulmonary melanoma metastasis using large area and label-free nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Hua, Daozhu; Qi, Shuhong; Li, Hui; Zhang, Zhihong; Fu, Ling

2012-06-01

We performed large area nonlinear optical microscopy (NOM) for label-free monitoring of the process of pulmonary melanoma metastasis ex vivo with subcellular resolution in C57BL/6 mice. Multiphoton autofluorescence (MAF) and second harmonic generation (SHG) images of lung tissue are obtained in a volume of ~2.2 mm×2.2 mm×30 μm. Qualitative differences in morphologic features and quantitative measurement of pathological lung tissues at different time points are characterized. We find that combined with morphological features, the quantitative parameters, such as the intensity ratio of MAF and SHG between pathological tissue and normal tissue and the MAF to SHG index versus depth clearly shows the tissue physiological changes during the process of pulmonary melanoma metastasis. Our results demonstrate that large area NOM succeeds in monitoring the process of pulmonary melanoma metastasis, which can provide a powerful tool for the research in tumor pathophysiology and therapy evaluation.

Gliosarcoma developing from an irradiated ependymoma.

PubMed

Kepes, J J; Bastian, F O; Weber, E D

1996-11-01

A 17-year-old girl was operated for a cystic mass located deep within the left parieto-occipital white matter. Histologically the tumor was an ependymoma with a vascular stroma. In spite of irradiation the tumor recurred locally twice, 1 and 2 years respectively after the original operation. The ependymoma portion of the tumor remained unchanged, but the stroma showed increased vascular hyperplasia at the time of the second operation and transformation into a fibrosarcoma in the third operative specimen. Proliferating cell markers (MIB-1) were positive only in the ependymoma cell nuclei in the first two specimens, but were also extensively present in the nuclei of the fibrosarcoma in the third specimen. In the latter, the fibrosarcoma portion greatly overwhelmed the residual ependymoma islands, but remained sharply delineated from them. This is the first observed case of a gliosarcoma originating from an ependymoma. The histological pattern of this mixed tumor clearly indicates that the source of the sarcomatous portions was the neoplastically transformed fibrovascular stroma of the original tumor, rather than "desmoplastic" alterations of the neoplastic ependymal cells themselves.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the "clustering" procedure, an initial assembly step for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, place the first of eight outboard fuel tanks (left) next to the central liquid-oxygen tank of S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the clustering procedure, an initial assembly step for the Saturn IB launch vehicle's S-IB (first) stage, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, place the first of eight outboard fuel tanks atop the central liquid-oxygen tank. Developed by the Marshall Space Flight Center and built by the Chrysler Corporation at Michoud Assembly Facility (MAF), the S-IB utilized eight H-1 engines and each produced 200,000 pounds of thrust, a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1969-01-01

In the clustering procedure, an initial assembly step for the first stage (S-IB stage) of the Saturn IB launch vehicle, workers at the Michoud Assembly Facility (MAF) near New Orleans, Louisiana, place the first of eight outboard fuel tanks next to the central liquid-oxygen tank of the S-IB stage. Developed by the Marshall Space Flight Center (MSFC) and built by the Chrysler Corporation at MAF, the S-IB stage utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Evidence for a gamma-interferon receptor that regulates macrophage tumoricidal activity

PubMed Central

1984-01-01

Gamma-interferon (IFN-gamma) is the macrophage-activating factor (MAF) produced by normal murine splenic cells and the murine T cell hybridoma 24/G1 that induces nonspecific tumoricidal activity in macrophages. Incubation of 24/G1 supernatants diluted to 8.3 IRU IFN-gamma/ml with 6 X 10(6) elicited peritoneal macrophages or bone marrow-derived macrophages for 4 h at 37 degrees C, resulted in removal of 80% of the MAF activity from the lymphokine preparation. Loss of activity appeared to result from absorption and not consumption because (a) 40% of the activity was removed after exposure to macrophage for 30 min at 4 degrees C, (b) no reduction of MAF activity was detected when the 24/G1 supernatant was incubated with macrophage culture supernatants, and (c) macrophage-treated supernatants showed a selective loss of MAF activity but not interleukin 2 (IL-2) activity. Absorption was dependent on the input of either IFN-gamma or macrophages and was time dependent at 37 degrees C but not at 4 degrees C. With four rodent species tested, absorption of murine IFN-gamma displayed species specificity. However, cultured human peripheral blood monocytes and the human histiocytic lymphoma cell line U937 were able to absorb the murine lymphokine. Although the majority of murine cell lines tested absorbed 24/G1 MAF activity, two murine macrophage cell lines, P388D1 and J774, were identified which absorbed significantly reduced amounts of natural IFN- gamma. Purified murine recombinant IFN-gamma was absorbed by elicited macrophages but not by P388D1. Normal macrophages but not P388D1 bound fluoresceinated microspheres coated with recombinant IFN-gamma and binding was inhibited by pretreatment of the normal cells with 24/G1 supernatants. Scatchard plot analysis showed that 12,000 molecules of soluble 125I-recombinant IFN-gamma bound per bone marrow macrophage with a Ka of 0.9 X 10(8) M-1. Binding was quantitatively inhibitable by natural IFN-gamma but not by murine IFN alpha. IFN

Infusing and selecting V&V activities

NASA Technical Reports Server (NTRS)

Feather, M. S.

2002-01-01

The evolving nature of software development poses a continuing series of challenges for V&V. In response, the V&V community selectively adapts the use of existing V&V activities, and introduces new and improved ones.

Application of Vibration and Oil Analysis for Reliability Information on Helicopter Main Rotor Gearbox

NASA Astrophysics Data System (ADS)

Murrad, Muhamad; Leong, M. Salman

Based on the experiences of the Malaysian Armed Forces (MAF), failure of the main rotor gearbox (MRGB) was one of the major contributing factors to helicopter breakdowns. Even though vibration and oil analysis are the effective techniques for monitoring the health of helicopter components, these two techniques were rarely combined to form an effective assessment tool in MAF. Results of the oil analysis were often used only for oil changing schedule while assessments of MRGB condition were mainly based on overall vibration readings. A study group was formed and given a mandate to improve the maintenance strategy of S61-A4 helicopter fleet in the MAF. The improvement consisted of a structured approach to the reassessment/redefinition suitable maintenance actions that should be taken for the MRGB. Basic and enhanced tools for condition monitoring (CM) are investigated to address the predominant failures of the MRGB. Quantitative accelerated life testing (QALT) was considered in this work with an intent to obtain the required reliability information in a shorter time with tests under normal stress conditions. These tests when performed correctly can provide valuable information about MRGB performance under normal operating conditions which enable maintenance personnel to make decision more quickly, accurately and economically. The time-to-failure and probability of failure information of the MRGB were generated by applying QALT analysis principles. This study is anticipated to make a dramatic change in its approach to CM, bringing significant savings and various benefits to MAF.

Substituting freshwater: Can ocean desalination and water recycling capacities substitute for groundwater depletion in California?

PubMed

Badiuzzaman, Pierre; McLaughlin, Eoin; McCauley, Darren

2017-12-01

While the sustainability of resource depletion is a longstanding environmental concern, wider attention has recently been given to growing water scarcity and groundwater depletion. This study seeks to test the substitutability assumption embedded in weak sustainability indicators using a case study of Californian water supply. The volume of groundwater depletion is used as a proxy for unsustainable water consumption, and defined by synthesising existing research estimates into low, medium and high depletion baselines. These are compared against projected water supply increases from ocean desalination and water recycling by 2035, to determine whether new, drought-proof water sources can substitute for currently unsustainable groundwater consumption. Results show that the maximum projected supply of new water, 2.47 million acre-feet per year (MAF/yr), is sufficient to meet low depletion estimates of 2.02 MAF/yr, but fails to come near the high depletion estimate of 3.44 MAF/yr. This does not necessarily indicate physical limitations of substitutability, but more so socio-economic limitations influenced by high comparative costs. By including capacities in demand-substitutability via urban water conservation, maximum predicted capacities reach 5.57 MAF/yr, indicating wide room for substitution. Based on these results, investment in social and institutional capital is an important factor to enhance demand-side substitutability of water and other natural resources, which has been somewhat neglected by the literature on the substitutability of natural resources. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of beta-major globin gene transcription is associated with recruitment of NF-E2 to the beta-globin LCR and gene promoter.

PubMed

Sawado, T; Igarashi, K; Groudine, M

2001-08-28

The mouse beta-globin gene locus control region (LCR), located upstream of the beta-globin gene cluster, is essential for the activated transcription of genes in the cluster. The LCR contains multiple binding sites for transactivators, including Maf-recognition elements (MAREs). However, little is known about the specific proteins that bind to these sites or the time at which they bind during erythroid differentiation. We have performed chromatin immunoprecipitation experiments to determine the recruitment of the erythroid-specific transactivator p45 NF-E2/MafK (p18 NF-E2) heterodimer and small Maf proteins to various regions in the globin gene locus before and after the induction of murine erythroleukemia (MEL) cell differentiation. We report that, before induction, the LCR is occupied by small Maf proteins, and, on erythroid maturation, the NF-E2 complex is recruited to the LCR and the active globin promoters, even though the promoters do not contain MAREs. This differentiation-coupled recruitment of NF-E2 complex correlates with a greater than 100-fold increase in beta-major globin transcription, but is not associated with a significant change in locus-wide histone H3 acetylation. These findings suggest that the beta-globin gene locus exists in a constitutively open chromatin conformation before terminal differentiation, and we speculate that recruitment of NF-E2 complex to the LCR and active promoters may be a rate-limiting step in the activation of beta-globin gene expression.

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

ClinicalTrials.gov

2017-09-07

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

76 FR 20835 - Amendment of VOR Federal Airways V-1, V-7, V-11 and V-20; Kona, HI

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

...; Airspace Docket No. 10-AWP-20] Amendment of VOR Federal Airways V-1, V-7, V-11 and V-20; Kona, HI AGENCY..., HI; V-1, V-7, V-11 and V-20. The FAA is taking this action due to procedural changes requiring..., (76 FR 13082), amends VOR Federal Airways V-1, V-7 V-11 and V-20; Kona, HI. These VHF Omnidirectional...

Geologic Mapping of V-19, V-28, and V-53

NASA Technical Reports Server (NTRS)

Stofan, E. R.; Martin, P.; Guest, J. E.

2008-01-01

The Sedna Planitia Quadrangle (V-19) extend from 25 deg N - 50 deg N latitude, 330 deg - 0 deg longitude. The quadrangle contains the northern-most portion of western Eistla Regio and the Sedna Planitia lowlands. Geologic maps of Sedna Planitia (V-199), Hecate Chasma (V-28) quadrangles have been completed at the 1:5,000,000 scale as part of the NASA Planetary Geologic Mapping Program. All quadrangles (V-53, V-28 and V-19) have been reviewed at lease once and will be resubmitted. In V-28 and V-53, more plains materials units have been mapped than in previously mapped quadrangles V-46 and V-39. V-19 is more comparable to these latter maps in terms of numbers of plains units. In V-28, all of the plains materials units to the south of the rift have an unusually high concentration of volcanic edifices, which both predate and postdate the units. A similar situation is seen in V-53 and V-19, where small edifice formation is not confined to any specific time period. In the two chasma-related quadrangles, coronae are located along the rift, as well as to the north and the south of the rifts. Coronae in both quadrangles exhibit all forms of corona topographic shapes, including depressions, rimmed depressions, plateaus and domes. In V-28 and V-53, some coronae along the rift do not have much associated volcanism; coronae with the most volcanism in these quadrangles are located at least 500 km off the rifts or on the Themis Regio highland. All three quadrangles have very horizontal stratigraphic columns, as limited contact between units prevents clear age determinations. While this results in the appearance that all units formed at the same time, the use of hachured columns for each unit illustrates the limited nature of our stratigraphic knowledge in these quadrangles, allowing for numerous possible geologic histories. The scale of resurfacing in these quadrangles is on the scale of 100s of kilometers, consistent with the fact that they lie in the most volcanic region of

Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study.

PubMed

Teslovich, Tanya M; Kim, Daniel Seung; Yin, Xianyong; Stancáková, Alena; Jackson, Anne U; Wielscher, Matthias; Naj, Adam; Perry, John R B; Huyghe, Jeroen R; Stringham, Heather M; Davis, James P; Raulerson, Chelsea K; Welch, Ryan P; Fuchsberger, Christian; Locke, Adam E; Sim, Xueling; Chines, Peter S; Narisu, Narisu; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Gudnason, Vilmundur; Musani, Solomon K; Jarvelin, Marjo-Riitta; Schellenberg, Gerard D; Speliotes, Elizabeth K; Kuusisto, Johanna; Collins, Francis S; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L

2018-05-01

Comprehensive metabolite profiling captures many highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serum amino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6 million genotyped and imputed variants in 8545 non-diabetic Finnish men from the METabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966). We identified five novel loci associated with amino acid levels (P = < 5×10-8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3×10-26); ZFHX3 (chr16:73326579, minor allele frequency (MAF) = 0.42%, P = 3.6×10-9), LIPC (rs10468017, P = 1.5×10-8), and WWOX (rs9937914, P = 3.8×10-8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8×10-9). Gene-based tests identified two novel genes harboring missense variants of MAF <1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5×10-6) and BCAT2 with valine (Pgene = 7.4×10-7); neither gene was implicated by single variant association tests. These findings are among the first applications of gene-based tests to identify new loci for amino acid levels. In addition to the seven novel gene associations, we identified five independent signals at established amino acid loci, including two rare variant signals at GLDC (rs138640017, MAF=0.95%, Pconditional = 5.8×10-40) with glycine levels and HAL (rs141635447, MAF = 0.46%, Pconditional = 9.4×10-11) with histidine levels. Examination of all single variant association results in our data revealed a strong inverse relationship between effect size and MAF (Ptrend<0.001). These novel signals provide further insight into the molecular mechanisms of amino acid metabolism and potentially, their perturbations in

Saturn Apollo Program

NASA Image and Video Library

1967-01-01

This photograph is a view of the Saturn V S-IC (first) test stage being hoisted into the S-IC-B1 test stand at the Mississippi Test Facility (MTF), Bay St. Louis, Mississippi. This stage was used to prove the operational readiness of the stand. Begirning operations in 1966, the MTF has two test stands; a dual-position structure for running the S-IC stage at full throttle, and two separate stands for the S-II (Saturn V third) stage. It became the focus of the static test firing program. The completed S-IC stage was shipped from the Michoud Assembly Facility (MAF) to the MTF. The stage was then installed into the 124-meter-high test stand for static firing tests before shipment to the Kennedy Space Center for final assembly of the Saturn V vehicle. The MTF was renamed to the National Space Technology Laboratory (NSTL) in 1974 and later to the Stennis Space Center (SSC) in May 1988.

Saturn Apollo Program

NASA Image and Video Library

1967-08-01

This photograph is a view of the Saturn V S-IC-5 (first) flight stage static test firing at the S-IC-B1 test stand at the Mississippi Test Facility (MTF), Bay St. Louis, Mississippi. Begirning operations in 1966, the MTF has two test stands, a dual-position structure for running the S-IC stage at full throttle, and two separate stands for the S-II (Saturn V third) stage. It became the focus of the static test firing program. The completed S-IC stage was shipped from Michoud Assembly Facility (MAF) to the MTF. The stage was then installed into the 407-foot-high test stand for the static firing tests before shipment to the Kennedy Space Center for final assembly of the Saturn V vehicle. The MTF was renamed to the National Space Technology Laboratory (NSTL) in 1974 and later to the Stennis Space Center (SSC) in May 1988.

Structural definition of a potent macrophage activating factor derived from vitamin D3-binding protein with adjuvant activity for antibody production.

PubMed

Yamamoto, N

1996-10-01

Incubation of human vitamin D3-binding protein (Gc protein), with a mixture of immobilized beta-galactosidase and sialidase, efficiently generated a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase, and isolation of the intermediates with immobilized lectins, revealed that either sequence of hydrolysis of Gc glycoprotein by these glycosidases yields the macrophage-activating factor, implying that Gc protein carries a trisaccharide composed of N-acetylgalactosamine and dibranched galactose and sialic acid termini. A 3 hr incubation of mouse peritoneal macrophages with picomolar amounts of the enzymatically generated macrophage-activating factor (GcMAF) resulted in a greatly enhanced phagocytic activity. Administration of a minute amount (10-50 pg/mouse) of GcMAF resulted in a seven- to nine-fold enhanced phagocytic activity of macrophages. Injection of sheep red blood cells (SRBC) along with GcMAF into mice produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days.

Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice.

PubMed

Aoki, Yuki; Ozawa, Tetsuo; Takemasa, Tohru; Numata, Osamu

2017-03-29

Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5' adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample "E80" from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K), and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy.

Combined approach for facial contour restoration: treatment of malar and cheek areas during rhytidectomy.

PubMed

Tapia, Antonio; Ruiz-de-Erenchun, Richard; Rengifo, Miguel

2006-08-01

One of the main objectives in facial lifting is to achieve an adequate facial contour, to enhance facial characteristics. Sometimes, facial areas are more or less accentuated, resulting in an unbalanced or inharmonious facial contour; this can be resolved in the context of a face lift. In the middle third of the face, two anatomical regions define the facial silhouette: the malar contour, with its bone support and superficial structures and, at the cheek level, intimately associated with the mastication system and the facial nerve, the buccal fat pad or Bichat fat pad. The authors describe their experience since 1998 using the double approach to malar atrophy and buccal fat pad hypertrophy in 194 patients with facial aging signs undergoing a face lift. All patients were offered a face lift with partial resection of the fat pad through facial incisions and a stronger malar projection using an inverse superficial musculoaponeurotic system flap. The main complications observed regarding this surgical technique, in order of appearance, were light asymmetry, caused by a persistent hematoma or swelling; paresthesia of the buccal and zygomatic branches, which resolved spontaneously; and a light sinking of the cheek caused by excessive resection. One patient underwent correction with a fat injection. The superior superficial musculoaponeurotic system flap and buccal fat pad resection provided excellent aesthetic results for a more harmonic and proportioned facial contour during rhytidectomy. Particularly in patients with round faces, the authors were able to obtain permanent malar symmetry and projection in addition to diminishing the cheek fullness.

Nonlinear Filtering Effects of Reservoirs on Flood Frequency Curves at the Regional Scale: RESERVOIRS FILTER FLOOD FREQUENCY CURVES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei; Li, Hong-Yi; Leung, L. Ruby

Anthropogenic activities, e.g., reservoir operation, may alter the characteristics of Flood Frequency Curve (FFC) and challenge the basic assumption of stationarity used in flood frequency analysis. This paper presents a combined data-modeling analysis of the nonlinear filtering effects of reservoirs on the FFCs over the contiguous United States. A dimensionless Reservoir Impact Index (RII), defined as the total upstream reservoir storage capacity normalized by the annual streamflow volume, is used to quantify reservoir regulation effects. Analyses are performed for 388 river stations with an average record length of 50 years. The first two moments of the FFC, mean annual maximummore » flood (MAF) and coefficient of variations (CV), are calculated for the pre- and post-dam periods and compared to elucidate the reservoir regulation effects as a function of RII. It is found that MAF generally decreases with increasing RII but stabilizes when RII exceeds a threshold value, and CV increases with RII until a threshold value beyond which CV decreases with RII. The processes underlying the nonlinear threshold behavior of MAF and CV are investigated using three reservoir models with different levels of complexity. All models capture the non-linear relationships of MAF and CV with RII, suggesting that the basic flood control function of reservoirs is key to the non-linear relationships. The relative roles of reservoir storage capacity, operation objectives, available storage prior to a flood event, and reservoir inflow pattern are systematically investigated. Our findings may help improve flood-risk assessment and mitigation in regulated river systems at the regional scale.« less

Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: support for a variable-size bottleneck

PubMed Central

Li, Mingkun; Rothwell, Rebecca; Vermaat, Martijn; Wachsmuth, Manja; Schröder, Roland; Laros, Jeroen F.J.; van Oven, Mannis; de Bakker, Paul I.W.; Bovenberg, Jasper A.; van Duijn, Cornelia M.; van Ommen, Gert-Jan B.; Slagboom, P. Eline; Swertz, Morris A.; Wijmenga, Cisca; Kayser, Manfred; Boomsma, Dorret I.; Zöllner, Sebastian; de Knijff, Peter; Stoneking, Mark

2016-01-01

Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies. PMID:26916109

V&V Within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1996-01-01

Verification and Validation (V&V) is used to increase the level of assurance of critical software, particularly that of safety-critical and mission-critical software. V&V is a systems engineering discipline that evaluates the software in a systems context, and is currently applied during the development of a specific application system. In order to bring the effectiveness of V&V to bear within reuse-based software engineering, V&V must be incorporated within the domain engineering process.

V & V Within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1996-01-01

Verification and validation (V&V) is used to increase the level of assurance of critical software, particularly that of safety-critical and mission critical software. This paper describes the working group's success in identifying V&V tasks that could be performed in the domain engineering and transition levels of reuse-based software engineering. The primary motivation for V&V at the domain level is to provide assurance that the domain requirements are correct and that the domain artifacts correctly implement the domain requirements. A secondary motivation is the possible elimination of redundant V&V activities at the application level. The group also considered the criteria and motivation for performing V&V in domain engineering.

Effects of synthetic sphingosine-1-phosphate analogs on cytosolic phospholipase A2alpha-independent release of arachidonic acid and cell toxicity in L929 fibrosarcoma cells: the structure-activity relationship.

PubMed

Shimizu, Masaya; Muramatsu, Yuki; Tada, Eiko; Kurosawa, Takeshi; Yamaura, Erika; Nakamura, Hiroyuki; Fujino, Hiromichi; Houjyo, Yuuya; Miyasaka, Yuri; Koide, Yuuki; Nishida, Atsushi; Murayama, Toshihiko

2009-03-01

Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells. Among the analogs tested, several compounds including DMB-mC11S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMB-mC9S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-nonyl)phenylpropyl phosphate] released AA within 1 h and caused cell death 6 h after treatment. The release of AA was observed in C12 cells [a L929 variant lacking a type alpha cytosolic phospholipase A(2) (cPLA(2)alpha)] and L929-cPLAalpha-siRNA cells (L929 cells treated with small interference RNA for cPLA(2)alpha). Treatment with pharmacological inhibitors of secretory and Ca(2+)-independent PLA(2)s decreased the DMB-mC11S-induced release of AA. The effect of the S1P analogs tested on the release of AA was comparable to that on cell death in L929 cells, and a high correlation coefficient was observed. Two analogs lacking a butoxycarbonyl moiety [DMAc-mC11S (dimethyl (2S,3R)-2-acetamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMAm-mC11S [dimethyl (2S,3R)-2-amino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate)] had inhibitory effects on the release of AA and cell toxicity induced by DMB-mC11S. Synthetic phosphorylated lipid analogs may be useful for studying PLA(2) activity and its toxicity in cells. [Supplementary Fig. 1: available only at http://dx.doi.org/10.1254/jphs.08284FP].

Label-free structural characterization of mitomycin C-modulated wound healing after photorefractive keratectomy by the use of multiphoton microscopy

NASA Astrophysics Data System (ADS)

Lo, Wen; Wang, Tsung-Jen; Chen, Wei-Liang; Hsueh, Chiu-Mei; Chen, Shean-Jen; Chen, Yang-Fang; Chou, Hsiu-Chu; Lin, Pi-Jung; Hu, Fung-Rong; Dong, Chen-Yuan

2010-05-01

We applied multiphoton autofluorescence (MAF) and second-harmonic generation (SHG) microscopy to monitor corneal wound healing after photorefractive keratectomy (PRK). Our results show that keratocyte activation can be observed by an increase in its MAF, while SHG imaging of corneal stroma can show the depletion of Bowman's layer after PRK and the reticular collagen deposition in the wound healing stage. Furthermore, quantification of the keratocyte activation and collagen deposition in conjunction with immunohistochemistry and histological images demonstrate the effectiveness of mitomycin C (MMC) in suppressing myofibroblast proliferation and collagen regeneration in the post-PRK wound healing process.

Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2018-02-08

Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma

Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2

PubMed Central

Nielson, Carrie M; Liu, Ching-Ti; Smith, Albert V; Ackert-Bicknell, Cheryl L; Reppe, Sjur; Jakobsdottir, Johanna; Wassel, Christina; Register, Thomas C; Oei, Ling; Alonso, Nerea; Oei, Edwin H; Parimi, Neeta; Samelson, Elizabeth J; Nalls, Mike A; Zmuda, Joseph; Lang, Thomas; Bouxsein, Mary; Latourelle, Jeanne; Claussnitzer, Melina; Siggeirsdottir, Kristin; Srikanth, Priya; Lorentzen, Erik; Vandenput, Liesbeth; Langefeld, Carl; Raffield, Laura; Terry, Greg; Cox, Amanda J; Allison, Matthew A; Criqui, Michael H; Bowden, Don; Ikram, M Arfan; Mellstrom, Dan; Karlsson, Magnus K; Carr, John; Budoff, Matthew; Phillips, Caroline; Cupples, L Adrienne; Chou, Wen-Chi; Myers, Richard H; Ralston, Stuart H; Gautvik, Kaare M; Cawthon, Peggy M; Cummings, Steven; Karasik, David; Rivadeneira, Fernando; Gudnason, Vilmundur; Orwoll, Eric S; Harris, Tamara B; Ohlsson, Claes; Kiel, Douglas P; Hsu, Yi-Hsiang

2017-01-01

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10−8) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10−10) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10−4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10−3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to linkSLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help

Sensing Traffic Density Combining V2V and V2I Wireless Communications.

PubMed

Sanguesa, Julio A; Barrachina, Javier; Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J; Cano, Juan-Carlos; Calafate, Carlos T; Manzoni, Pietro

2015-12-16

Wireless technologies are making the development of new applications and services in vehicular environments possible since they enable mobile communication between vehicles (V2V), as well as communication between vehicles and infrastructure nodes (V2I). Usually, V2V communications are dedicated to the transmission of small messages mainly focused on improving traffic safety. Instead, V2I communications allow users to access the Internet and benefit from higher level applications. The combination of both V2V and V2I, known as V2X communications, can increase the benefits even further, thereby making intelligent transportation systems (ITS) a reality. In this paper, we introduce V2X-d, a novel architecture specially designed to estimate traffic density on the road. In particular, V2X-d exploits the combination of V2V and V2I communications. Our approach is based on the information gathered by sensors (i.e., vehicles and road side units (RSUs)) and the characteristics of the roadmap topology to accurately make an estimation of the instant vehicle density. The combination of both mechanisms improves the accuracy and coverage area of the data gathered, while increasing the robustness and fault tolerance of the overall approach, e.g., using the information offered by V2V communications to provide additional density information in areas where RSUs are scarce or malfunctioning. By using our collaborative sensing scheme, future ITS solutions will be able to establish adequate dissemination protocols or to apply more efficient traffic congestion reduction policies, since they will be aware of the instantaneous density of vehicles.

Sensing Traffic Density Combining V2V and V2I Wireless Communications

PubMed Central

Sanguesa, Julio A.; Barrachina, Javier; Fogue, Manuel; Garrido, Piedad; Martinez, Francisco J.; Cano, Juan-Carlos; Calafate, Carlos T.; Manzoni, Pietro

2015-01-01

Wireless technologies are making the development of new applications and services in vehicular environments possible since they enable mobile communication between vehicles (V2V), as well as communication between vehicles and infrastructure nodes (V2I). Usually, V2V communications are dedicated to the transmission of small messages mainly focused on improving traffic safety. Instead, V2I communications allow users to access the Internet and benefit from higher level applications. The combination of both V2V and V2I, known as V2X communications, can increase the benefits even further, thereby making intelligent transportation systems (ITS) a reality. In this paper, we introduce V2X-d, a novel architecture specially designed to estimate traffic density on the road. In particular, V2X-d exploits the combination of V2V and V2I communications. Our approach is based on the information gathered by sensors (i.e., vehicles and road side units (RSUs)) and the characteristics of the roadmap topology to accurately make an estimation of the instant vehicle density. The combination of both mechanisms improves the accuracy and coverage area of the data gathered, while increasing the robustness and fault tolerance of the overall approach, e.g., using the information offered by V2V communications to provide additional density information in areas where RSUs are scarce or malfunctioning. By using our collaborative sensing scheme, future ITS solutions will be able to establish adequate dissemination protocols or to apply more efficient traffic congestion reduction policies, since they will be aware of the instantaneous density of vehicles. PMID:26694405

Survey of NASA V and V Processes/Methods

NASA Technical Reports Server (NTRS)

Pecheur, Charles; Nelson, Stacy

2002-01-01

The purpose of this report is to describe current NASA Verification and Validation (V&V) techniques and to explain how these techniques are applicable to 2nd Generation RLV Integrated Vehicle Health Management (IVHM) software. It also contains recommendations for special V&V requirements for IVHM. This report is divided into the following three sections: 1) Survey - Current NASA V&V Processes/Methods; 2) Applicability of NASA V&V to 2nd Generation RLV IVHM; and 3) Special 2nd Generation RLV IVHM V&V Requirements.

Mitochondrial dynamics and respiration within cells with increased open pore cytoskeletal meshes

PubMed Central

Jang, David H.; Seeger, Sarah C.; Grady, Martha E.; Shofer, Frances S.

2017-01-01

ABSTRACT The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of

Genome-Wide Meta-Analysis of Sciatica in Finnish Population.

PubMed

Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppälä, Ilkka; Juonala, Markus; Kähönen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T; Lehtimäki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti

2016-01-01

Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6) were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6-7%) than in other European populations (1-2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate.

Genome-Wide Meta-Analysis of Sciatica in Finnish Population

PubMed Central

Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppälä, Ilkka; Juonala, Markus; Kähönen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T.; Lehtimäki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti

2016-01-01

Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6) were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6–7%) than in other European populations (1–2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate. PMID:27764105

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts.

PubMed

Bouwman, Aniek C; Hayes, Ben J; Calus, Mario P L

2017-10-30

Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of allele counts results in less shrinkage towards the mean for low minor allele frequency (MAF) variants. Scaling may become relevant for estimating ASE as more low MAF variants will be used in genomic evaluations. We show the impact of scaling on estimates of ASE using real data and a theoretical framework, and in terms of power, model fit and predictive performance. In a dairy cattle dataset with 630 K SNP genotypes, the correlation between DGV for stature from a random regression model using centered allele counts (RRc) and centered and scaled allele counts (RRcs) was 0.9988, whereas the overall correlation between ASE using RRc and RRcs was 0.27. The main difference in ASE between both methods was found for SNPs with a MAF lower than 0.01. Both the ratio (ASE from RRcs/ASE from RRc) and the regression coefficient (regression of ASE from RRcs on ASE from RRc) were much higher than 1 for low MAF SNPs. Derived equations showed that scenarios with a high heritability, a large number of individuals and a small number of variants have lower ratios between ASE from RRc and RRcs. We also investigated the optimal scaling parameter [from - 1 (RRcs) to 0 (RRc) in steps of 0.1] in the bovine stature dataset. We found that the log-likelihood was maximized with a scaling parameter of - 0.8, while the mean squared error of prediction was minimized with a scaling parameter of - 1, i.e., RRcs. Large differences in estimated ASE were observed for low MAF SNPs when allele counts were scaled or not scaled because there is less shrinkage towards the mean for scaled allele counts. We derived a theoretical framework that shows that the difference in ASE due to shrinkage is heavily influenced by the

Future water demand in California under a broad range of land use scenarios

NASA Astrophysics Data System (ADS)

Wilson, T. S.; Sleeter, B. M.; Cameron, D. R.

2016-12-01

California continues to be gripped by the most severe drought on record. Most general circulation models agree the state will continue to warm this century and research suggests persistent, long-term droughts may become the new normal, exacerbating an already uncertain water supply future. Population increases and agricultural intensification will likely stress existing, highly variable inter-annual water supplies even further in coming decades. Using the Land Use and Carbon Scenario Simulator (LUCAS) model, we explore a wide range of potential water demand futures from 2012 to 2062 based on 8 alternative, spatially-explicit (1 km) land use scenarios and land-use related water demand. Scenarios include low and high rates for urbanization, agricultural expansion, and agricultural contraction as well as lowest and highest rates for the combined suite of anthropogenic land uses. Land change values were sampled from county-level historical (1991-2012) land change data and county-level average water use data for urban areas (i.e. municipal and industrial) and annual and perennial cropland. We modeled 100 Monte Carlo simulations for each scenario to better characterize and capture model uncertainty and a range of potential future outcomes. Results show water demand in Mediterranean California was lowest in the low anthropogenic change scenario, dropping an average 2.7 million acre feet (MAF) by 2062. The highest water demand was seen in the high urbanization (+3.2 MAF), high agricultural expansion (+4.1 MAF), and the high anthropogenic (+4.3 MAF) scenarios. Results provide water managers and policy makers with information on diverging land use and water use futures, based on observed land change and water use trends, helping better inform land and resource management decisions.

Development of a cell-based high throughput luciferase enzyme fragment complementation assay to identify nuclear-factor-e2-related transcription factor 2 activators.

PubMed

Xie, Wensheng; Pao, Christina; Graham, Taylor; Dul, Ed; Lu, Quinn; Sweitzer, Thomas D; Ames, Robert S; Li, Hu

2012-12-01

Nuclear-factor-E2-related transcription factor 2 (Nrf2) regulates a large panel of Phase II genes and plays an important role in cell survival. Nrf2 activation has been shown as preventing cigarette smoke-induced alveolar enlargement in mice. Therefore, activation of the Nrf2 protein by small-molecule activators represents an attractive therapeutic strategy that is used for chronic obstructive pulmonary disease. In this article, we describe a cell-based luciferase enzyme fragment complementation assay that identifies Nrf2 activators. This assay is based on the interaction of Nrf2 with its nuclear partner MafK or runt-related transcription factor 2 (RunX2) and is dependent on the reconstitution of a "split" luciferase. Firefly luciferase is split into two fragments, which are genetically fused to Nrf2 and MafK or RunX2, respectively. BacMam technology was used to deliver the fusion constructs into cells for expression of the tagged proteins. When the BacMam-transduced cells were treated with Nrf2 activators, the Nrf2 protein was stabilized and translocated into the nucleus where it interacted with MafK or RunX2. The interaction of Nrf2 and MafK or RunX2 brought together the two luciferase fragments that form an active luciferase. The assay was developed in a 384-well format and was optimized by titrating the BacMam concentration, transduction time, cell density, and fetal bovine serum concentration. It was further validated with known Nrf2 activators. Our data show that this assay is robust, sensitive, and amenable to high throughput screening of a large compound collection for the identification of novel Nrf2 activators.

Along-the-net reconstruction of hydropower potential with consideration of anthropic alterations

NASA Astrophysics Data System (ADS)

Masoero, A.; Claps, P.; Gallo, E.; Ganora, D.; Laio, F.

2014-09-01

Even in regions with mature hydropower development, requirements for stable renewable power sources suggest revision of plans of exploitation of water resources, while taking care of the environmental regulations. Mean Annual Flow (MAF) is a key parameter when trying to represent water availability for hydropower purposes. MAF is usually determined in ungauged basins by means of regional statistical analysis. For this study a regional estimation method consistent along-the-river network has been developed for MAF estimation; the method uses a multi-regressive approach based on geomorphoclimatic descriptors, and it is applied on 100 gauged basins located in NW Italy. The method has been designed to keep the estimates of mean annual flow congruent at the confluences, by considering only raster-summable explanatory variables. Also, the influence of human alterations in the regional analysis of MAF has been studied: impact due to the presence of existing hydropower plants has been taken into account, restoring the "natural" value of runoff through analytical corrections. To exemplify the representation of the assessment of residual hydropower potential, the model has been applied extensively to two specific mountain watersheds by mapping the estimated mean flow for the basins draining into each pixel of a the DEM-derived river network. Spatial algorithms were developed using the OpenSource Software GRASS GIS and PostgreSQL/PostGIS. Spatial representation of the hydropower potential was obtained using different mean flow vs hydraulic-head relations for each pixel. Final potential indices have been represented and mapped through the Google Earth platform, providing a complete and interactive picture of the available potential, useful for planning and regulation purposes.

Psychometric properties of the Multidimensional Assessment of Fatigue scale in traumatic brain injury: an NIDRR Traumatic Brain Injury Model Systems study.

PubMed

Lequerica, Anthony; Bushnik, Tamara; Wright, Jerry; Kolakowsky-Hayner, Stephanie A; Hammond, Flora M; Dijkers, Marcel P; Cantor, Joshua

2012-01-01

To investigate the psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale in a traumatic brain injury (TBI) sample. Prospective survey study. Community. One hundred sixty-seven individuals with TBI admitted for inpatient rehabilitation, enrolled into the TBI Model Systems national database, and followed up at either the first or second year postinjury. Not applicable. Multidimensional Assessment of Fatigue. The initial analysis, using items 1 to 14, which are based on a 10-point rating scale, found that only 1 item ("walking") misfit the overall construct of fatigue in this TBI population. However, this 10-point rating scale was found to have disordered thresholds. When ratings were collapsed into 4 response categories, all MAF items used to calculate the Global Fatigue Index formed a unidimensional scale. Findings generally support the unidimensionality of the MAF when used in a TBI population but call into question the use of a 10-point rating scale for items 1 to 14. Further study is needed to investigate the use of a 4-category rating scale across all items and the fit of the "walking" item for a measure of fatigue among individuals with TBI.

As(V) and Sb(V) co-adsorption onto ferrihydrite: synergistic effect of Sb(V) on As(V) under competitive conditions.

PubMed

Wu, Debo; Sun, Sheng-Peng; He, Minghe; Wu, Zhangxiong; Xiao, Jie; Chen, Xiao Dong; Wu, Winston Duo

2018-05-01

Competitive adsorption of As(V) and Sb(V) at environmentally relevant concentrations onto ferrihydrite was investigated. Batch experiments and XPS analyses confirmed that in a binary system, the presence of Sb(V) exhibited a slight synergistic effect on As(V) adsorption. XPS analyses showed that As(V) and Sb(V) adsorption led to obvious diminishment of Fe-O-Fe and Fe-O-H bonds respectively. At pH of 9, a more significant decrease of Fe-O-Fe was observed in the binary system than that in a single system, indicating that As(V) displayed an even stronger interaction with lattice oxygen atoms under competitive conditions. Basically, ionic strength demonstrated a negligible or positive influence on As(V) and Sb(V) adsorption in binary system. Study of adsorption sequence also indicated that the presence of Sb(V) showed a promotion effect on As(V) adsorption at neutral pHs. Considering that co-contamination of As and Sb in waters has been of great concern throughout the world, our findings contributed to a better understanding of their distribution, mobility, and fate in environment.

Purified umbilical cord derived mesenchymal stem cell treatment in a case of systemic lupus erythematosus.

PubMed

Phillips, Christopher D; Wongsaisri, Pornpatcharin; Htut, Thein; Grossman, Terry

2017-12-01

Systemic lupus erythematosus (SLE) is a multiple organ system autoimmune disorder for which there is no known cure. We report a case of a young adult lady with SLE and Sjogren's with diagnostic and clinical resolution following purified umbilical cord derived mesenchymal stem cell (MSC) and globulin component protein macrophage activating factor (GcMAF) therapy in a combined multidisciplinary integrative medicine protocol. Our patient had complete reversal of all clinical and laboratory markers. We recommend a prospective randomized double blind study to assess the sustained efficacy of MSC and GcMAF in the treatment of autoimmune connective tissue diseases such as systemic lupus erythematosus.

INTERFERON α ACTIVATES NF-κ B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

PubMed Central

Yang, Chuan He; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence M.

2005-01-01

In addition to activating members of the STAT transcription factor family, IFN α/β activates the NF-κ B transcription factor. To determine the role of the JAK-STAT pathway in NF-κ B activation by IFN, we examined NF-κ B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH) IFN activates STAT1, STAT2 and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells IFN induces NF-κB activation and NF-κB dependent gene transcription, but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically-inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF-κB activation requires only TYK2. PMID:15883164

75 FR 6860 - Airworthiness Directives; International Aero Engines AG (IAE) V2500-A1, V2522-A5, V2524-A5, V2525...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-12

... Airworthiness Directives; International Aero Engines AG (IAE) V2500-A1, V2522-A5, V2524-A5, V2525-D5, V2527-A5, V2527E-A5, V2527M-A5, V2528-D5, V2530-A5, and V2533-A5 Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for all International Aero Engines AG (IAE) V2500-A1, V2525-D5 and V2528-D5...

V&V of Fault Management: Challenges and Successes

NASA Technical Reports Server (NTRS)

Fesq, Lorraine M.; Costello, Ken; Ohi, Don; Lu, Tiffany; Newhouse, Marilyn

2013-01-01

This paper describes the results of a special breakout session of the NASA Independent Verification and Validation (IV&V) Workshop held in the fall of 2012 entitled "V&V of Fault Management: Challenges and Successes." The NASA IV&V Program is in a unique position to interact with projects across all of the NASA development domains. Using this unique opportunity, the IV&V program convened a breakout session to enable IV&V teams to share their challenges and successes with respect to the V&V of Fault Management (FM) architectures and software. The presentations and discussions provided practical examples of pitfalls encountered while performing V&V of FM including the lack of consistent designs for implementing faults monitors and the fact that FM information is not centralized but scattered among many diverse project artifacts. The discussions also solidified the need for an early commitment to developing FM in parallel with the spacecraft systems as well as clearly defining FM terminology within a project.

75 FR 43813 - Modification of VOR Federal Airways V-82, V-175, V-191, and V-430 in the Vicinity of Bemidji, MN

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

...-0241; Airspace Docket No. 10-AGL-4] RIN 2120-AA66 Modification of VOR Federal Airways V-82, V-175, V-191, and V-430 in the Vicinity of Bemidji, MN AGENCY: Federal Aviation Administration (FAA), DOT...) Federal Airways V-82, V-175, V-191, and V- 430 in the vicinity of Bemidji, MN. The Bemidji (BJI) VOR, that...

High-resolution infrared studies of the v 10, v 11, v 14, and v 18 levels of [1.1.1]propellane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirkpatrick, Robynne W.; Masiello, Tony; Martin, Matthew A.

2012-11-15

This paper is a continuation of earlier work for which the high resolution infrared spectrum of [1.1.1]propellane was measured and its k and l structure resolved for the first time. Here we present results from an analysis of more than 16,000 transitions involving three fundamental bands v 10 (E'-A1'), v 11 (E'-A1'), v 14 (A2''-A1') and two difference bands (v 10- v 18) (E'-E'') and (v 11-v 18) (E'-E"). Additional information about v18 was also obtained from the difference band (v 15+v 18)-v 18 (E'-E") and the binary combination band (v 15+v 18) (E'-A1'). Through the use of the groundmore » state constants reported in an earlier paper [1], rovibrational constants have been determined for all the vibrational states involved in these bands. The rovibrational parameters for the v 18(E'') state were obtained from combination-differences and showed no need to include interactions with other states. The v 10(E') state analysis was also straight-forward, with only a weak Coriolis interaction with the levels of the v 14(A2'') state. The latter levels are much more affected by a strong Coriolis interaction with the levels of the nearby v 11(E') state and also by a small but significant interaction with another state, presumably the v16(E'') state, that is not directly observed. Gaussian calculations (B3LYP/cc-pVTZ) computed at the anharmonic level aided the analyses by providing initial values for many of the parameters. These theoretical results generally compare favorably with the final parameter values deduced from the spectral analyses. Finally, evidence was obtained for several level crossings between the rotational levels of the v 11 and v 14 states and, using a weak coupling term corresponding to a Δk = ±5, Δl = ∓1 matrix element, it was possible to find transitions from the ground state that, combined with transitions to the same upper state, give a value of C 0 = 0.1936519(4) cm -1. This result, combined with the value of B 0 = 0.28755833(14) cm-1 reported

Ultrasound skin tightening.

PubMed

Minkis, Kira; Alam, Murad

2014-01-01

Ultrasound skin tightening is a noninvasive, nonablative method that allows for energy deposition into the deep dermal and subcutaneous tissue while avoiding epidermal heating. Ultrasound coagulation is confined to arrays of 1-mm(3) zones that include the superficial musculoaponeurotic system and connective tissue. This technology gained approval from the Food and Drug Administration as the first energy-based skin "lifting" device, specifically for lifting lax tissue on the neck, submentum, and eyebrows. Ultrasound has the unique advantage of direct visualization of treated structures during treatment. Ultrasound is a safe and efficacious treatment for mild skin tightening and lifting. Copyright © 2014 Elsevier Inc. All rights reserved.

Successful Management of Aggressive Fibromatosis of the Neck: A Case Report

PubMed

Avinçsal, Özgür Mehmet; Shinomiya, Hirotaka; Otsuki, Naoki; Sasaki, Ryohei; Nibu, Ken-ichi

2018-05-29

Aggressive fibromatoses are histologically benign fibrous neoplasms originating from musculoaponeurotic structures throughout the body. They are locally invasive and erode adjacent vital structures. The head and neck region constitutes 7-25% of all extra-abdominal cases. Here, we report the case of a patient with aggressive fibromatosis in the left side of the neck. While the tumor deeply invaded the scalene muscles, the lesion was successfully treated by surgery followed by radiotherapy. The patient has been disease free for the last 7 years following treatment. Due to its unusual location in the head and neck region, aggressive fibromatosis should be considered in the differential diagnosis of invading lesions of the neck.

Expert system verification and validation study: ES V/V Workshop

NASA Technical Reports Server (NTRS)

French, Scott; Hamilton, David

1992-01-01

The primary purpose of this document is to build a foundation for applying principles of verification and validation (V&V) of expert systems. To achieve this, some V&V as applied to conventionally implemented software is required. Part one will discuss the background of V&V from the perspective of (1) what is V&V of software and (2) V&V's role in developing software. Part one will also overview some common analysis techniques that are applied when performing V&V of software. All of these materials will be presented based on the assumption that the reader has little or no background in V&V or in developing procedural software. The primary purpose of part two is to explain the major techniques that have been developed for V&V of expert systems.

The spectrum of metanephric adenofibroma and related lesions: clinicopathologic study of 25 cases from the National Wilms Tumor Study Group Pathology Center.

PubMed

Arroyo, M R; Green, D M; Perlman, E J; Beckwith, J B; Argani, P

2001-04-01

The authors report nine new metanephric adenofibroma (MAFs; previously termed nephrogenic adenofibroma) and 16 related tumors from the files of the National Wilms Tumor Study Group Pathology Center (NWTSGPC). All tumors contained a variable amount of a bland spindle cell stroma, which is essentially identical to the recently described metanephric stromal tumor (MST). Features that distinguish this stroma from congenital mesoblastic nephroma (CMN) include intratumoral angiodysplasia, concentric cuffing of entrapped tubules ("onion skinning"), and heterologous differentiation. The epithelial components of these lesions spanned a wide range of appearances. All tumors contained at least focally an inactive embryonal epithelium identical morphologically to metanephric adenoma (MA), and hence each case could be classified as containing MAF. The epithelium of nine tumors had this appearance throughout, and hence these were considered usual MAFs. The epithelium of four tumors demonstrated increased mitotic activity but was otherwise similar to MA. The epithelial component of seven tumors spanned a morphologic spectrum from inactive MA to malignant epithelial predominant Wilms tumor (WT), with gradual transitions noted in several cases. Five other tumors contained a carcinomatous component distinct from these lesions but identical morphologically to papillary renal cell carcinoma (PRCC). In one of these cases, this component had metastasized to the regional lymph nodes at the time of diagnosis. No tumor recurred during follow-up, although almost all patients received adjuvant therapy for WT regardless of their tumor's histology and NWTSGPC diagnosis. In conclusion, MAF is a biphasic tumor that spans the morphologic spectrum between benign pure stromal (MST) and pure epithelial (MA) lesions, and can merge with the morphology of WT, supporting the concept that these are all related lesions. A relationship to PRCC is also evident.

Novel Genetic Loci Associated with Retinal Microvascular Diameter

PubMed Central

Jensen, Richard A.; Sim, Xueling; Smith, Albert Vernon; Li, Xiaohui; Jakobsdóttir, Jóhanna; Cheng, Ching-Yu; Brody, Jennifer A.; Cotch, Mary Frances; Mcknight, Barbara; Klein, Ronald; Wang, Jie Jin; Kifley, Annette; Harris, Tamara B.; Launer, Lenore J.; Taylor, Kent D.; Klein, Barbara E.K.; Raffel, Leslie J.; Li, Xiang; Ikram, M. Arfan; Klaver, Caroline C.; van der Lee, Sven J.; Mutlu, Unal; Hofman, Albert; Uitterlinden, Andre G.; Liu, Chunyu; Kraja, Aldi T.; Mitchell, Paul; Gudnason, Vilmundur; Rotter, Jerome I.; Boerwinkle, Eric; van Duijn, Cornelia M.; Psaty, Bruce M.; Wong, Tien Y.

2015-01-01

Background There is increasing evidence that retinal microvascular diameters are associated with cardio- and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. Methods and Results This study extends previous genome-wide association study results using 24,000+ multi-ethnic participants from 7 discovery and 5,000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single nucleotide polymorphisms (SNPs) and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent (CRVE) and the central retinal arteriole equivalent (CRAE). We report 4 new loci associated with CRVE, one of which is also associated with CRAE. The 4 SNPs are rs7926971 in TEAD1 (p=3.1×10−11, minor allele frequency (MAF)=0.43), rs201259422 in TSPAN10 (p=4.4×10−9, MAF=0.27), rs5442 in GNB3 (p=7.0×10−10, MAF=0.05) and rs1800407 in OCA2 (p=3.4×10−8, MAF=0.05). The latter SNP, rs1800407, was also associated with CRAE (p=6.5×10−12). Results from the gene-based burden tests were null. In phenotype look-ups, SNP rs201255422 was associated with both systolic (p=0.001) and diastolic blood pressure (p=8.3×10−04). Conclusions Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease. PMID:26567291

Effects of flavonoids from Martynia annua and Tephrosia purpurea on cutaneous wound healing

PubMed Central

Lodhi, Santram; Jain, Avijeet; Jain, Alok Pal; Pawar, Rajesh Singh; Singhai, Abhay Kumar

2016-01-01

Objective: Martynia annua L. (M. annua), (Martyniaccae) has been traditionally used in the treatment of epilepsy, sore throat and inflammatory disorders. The leaf paste is used topically on Tuberculosis of the lymphatic glands and wounds of domestic animals. Tephrosia purpurea (T. purpurea), (Fabaceae) has been used traditionally as a remedy for asthma, gonorrhea, rheumatism and ulcers. This study aimed to evaluate the potential wound healing effects of different fractions ofethanol extract of M. annua leaves and aerial parts of T. purpurea. Materials and Methods: Methanol fraction of M. annua (MAF-C) and ethyl acetate fraction of T. purpurea (TPF-A) were evaluated for healing potential in dead-space and burn wound models. An ointment (5% w/w) of MAF-C and TPF-A, pongamol (0.2 and 0.5% w/w) and luteolin (0.2 and 0.5% w/w) was applied topically twice a day. The effects were compared with Povidone Iodine ointment with respect to protein, collagen content, enzymatic assay and histopathological finding of granuloma tissues. Results: Ethanol extracts of M. annua and T. purpureawere exhibited total flavonoid contents of 126.2 ± 4.69 and 171.6 ± 6.38 mg (quercetin equivalent), respectively. HPLC fingerprinting confirmed the presence of luteolin in M. annua and quercetin in T. purpurea. TPF-A and MAF-C ointments (5% w/w) significantly increases the hydroxyproline and protein contents. Luteolin and pongamol ointments were also found to be effective in both wound models. Conclusion: Our findings suggested that 5% w/w ointment of TPF-A and MAF-C fractions were more effective than isolated flavonoids in wound healing which may be due to synergistic interactions between the flavonoids and other constituents. PMID:27761428

Spatio-Temporal Distribution of Mycobacterium tuberculosis Complex Strains in Ghana.

PubMed

Yeboah-Manu, Dorothy; Asare, P; Asante-Poku, A; Otchere, I D; Osei-Wusu, S; Danso, E; Forson, A; Koram, K A; Gagneux, Sebastien

2016-01-01

There is a perception that genomic differences in the species/lineages of the nine species making the Mycobacterium tuberculosis complex (MTBC) may affect the efficacy of distinct control tools in certain geographical areas. We therefore analyzed the prevalence and spatial distribution of MTBC species and lineages among isolates from pulmonary TB cases over an 8-year period, 2007-2014. Mycobacterial species isolated by culture from consecutively recruited pulmonary tuberculosis patients presenting at selected district/sub-district health facilities were confirmed as MTBC by IS6110 and rpoß PCR and further assigned lineages and sub lineages by spoligotyping and large sequence polymorphism PCR (RDs 4, 9, 12, 702, 711) assays. Patient characteristics, residency, and risks were obtained with a structured questionnaire. We used SaTScan and ArcMap analyses to identify significantly clustered MTBC lineages within selected districts and spatial display, respectively. Among 2,551 isolates, 2,019 (79.1%), 516 (20.2%) and 16 (0.6%) were identified as M. tuberculosis sensu stricto (MTBss), M. africanum (Maf), 15 M. bovis and 1 M. caprae, respectively. The proportions of MTBss and Maf were fairly constant within the study period. Maf spoligotypes were dominated by Spoligotype International Type (SIT) 331 (25.42%), SIT 326 (15.25%) and SIT 181 (14.12%). We found M. bovis to be significantly higher in Northern Ghana (1.9% of 212) than Southern Ghana (0.5% of 2339) (p = 0.020). Using the purely spatial and space-time analysis, seven significant MTBC lineage clusters (p< 0.05) were identified. Notable among the clusters were Ghana and Cameroon sub-lineages found to be associated with north and south, respectively. This study demonstrated that overall, 79.1% of TB in Ghana is caused by MTBss and 20% by M. africanum. Unlike some West African Countries, we did not observe a decline of Maf prevalence in Ghana.

Mercury Atomic Frequency Standards for Space Based Navigation and Timekeeping

NASA Technical Reports Server (NTRS)

Tjoelker, R. L.; Burt, E. A.; Chung, S.; Hamell, R. L.; Prestage, J. D.; Tucker, B.; Cash, P.; Lutwak, R.

2012-01-01

A low power Mercury Atomic Frequency Standard (MAFS) has been developed and demonstrated on the path towards future space clock applications. A self contained mercury ion breadboard clock: emulating flight clock interfaces, steering a USO local oscillator, and consuming approx 40 Watts has been operating at JPL for more than a year. This complete, modular ion clock instrument demonstrates that key GNSS size, weight, and power (SWaP) requirements can be achieved while still maintaining short and long term performance demonstrated in previous ground ion clocks. The MAFS breadboard serves as a flexible platform for optimizing further space clock development and guides engineering model design trades towards fabrication of an ion clock for space flight.

Ares I Crew Launch Vehicle Upper Stage Element Overview

NASA Technical Reports Server (NTRS)

McArthur, J. Craig

2008-01-01

This viewgraph presentation gives an overview of NASA's Ares I Crew Launch Vehicle Upper Stage Element. The topics include: 1) What is NASA s Mission?; 2) NASA s Exploration Roadmap What is our time line?; 3) Building on a Foundation of Proven Technologies Launch Vehicle Comparisons; 4) Ares I Upper Stage; 5) Upper Stage Primary Products; 6) Ares I Upper Stage Development Approach; 7) What progress have we made?; 8) Upper Stage Subsystem Highlights; 9) Structural Testing; 10) Common Bulkhead Processing; 11) Stage Installation at Stennis Space Center; 12) Boeing Producibility Team; 13) Upper Stage Low Cost Strategy; 14) Ares I and V Production at Michoud Assembly Facility (MAF); 15) Merged Manufacturing Flow; and 16) Manufacturing and Assembly Weld Tools.

Limiting glioma development by photodynamic therapy-generated macrophage vaccine and allo-stimulation: an in vivo histological study in rats

NASA Astrophysics Data System (ADS)

Madsen, Steen J.; Christie, Catherine; Huynh, Khoi; Peng, Qian; Uzal, Francisco A.; Krasieva, Tatiana B.; Hirschberg, Henry

2018-02-01

Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site. Experiments were conducted in an in vivo brain tumor development model using Fischer rats and F98 (syngeneic) and BT4C (allogeneic) glioma cells. The results showed that immunization with Ma (acting as antigen-presenting cells), primed with PDT-treated tumor cells (MaF98), significantly slowed but did not prevent the growth of F98-induced tumors in the brain. Complete suppression of tumor development was obtained via MaF98 inoculation combined with direct intracranial injection of allogeneic glioma cells. No deleterious effects were noted in any of the animals during the 14-day observation period.

Auditory Masking Effects on Speech Fluency in Apraxia of Speech and Aphasia: Comparison to Altered Auditory Feedback

PubMed Central

Haley, Katarina L.

2015-01-01

Purpose To study the effects of masked auditory feedback (MAF) on speech fluency in adults with aphasia and/or apraxia of speech (APH/AOS). We hypothesized that adults with AOS would increase speech fluency when speaking with noise. Altered auditory feedback (AAF; i.e., delayed/frequency-shifted feedback) was included as a control condition not expected to improve speech fluency. Method Ten participants with APH/AOS and 10 neurologically healthy (NH) participants were studied under both feedback conditions. To allow examination of individual responses, we used an ABACA design. Effects were examined on syllable rate, disfluency duration, and vocal intensity. Results Seven of 10 APH/AOS participants increased fluency with masking by increasing rate, decreasing disfluency duration, or both. In contrast, none of the NH participants increased speaking rate with MAF. In the AAF condition, only 1 APH/AOS participant increased fluency. Four APH/AOS participants and 8 NH participants slowed their rate with AAF. Conclusions Speaking with MAF appears to increase fluency in a subset of individuals with APH/AOS, indicating that overreliance on auditory feedback monitoring may contribute to their disorder presentation. The distinction between responders and nonresponders was not linked to AOS diagnosis, so additional work is needed to develop hypotheses for candidacy and underlying control mechanisms. PMID:26363508

GammeV and GammeV-CHASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wester, W.; /Fermilab

2011-11-01

Physics beyond the Standard Model might include Weakly Interacting Slim Particles (WISPs) that address questions such as what is the nature of dark matter or even shed insight into the underlying nature of dark energy. WISPs are a general class of particles that include axions, axion-like particles, hidden sector photons, milli-charged particles, chameleons, etc. The GammeV (Gamma to milli-eV) experiment originated in 2007 in order to test a positive anomalous axion-like particle interpretation of the PVLAS experiment which was not evident in subsequent data. The experiment was also motivated as it was realized that the milli-eV scale appears naturally inmore » a see-saw between the electroweak and Planck scales, neutrino mass differences, the dark energy density, and the possible mass for certain dark matter candidates. GammeV was first to exclude both a scalar and pseudoscalar axion-like particle interpretation of the anomalous PVLAS result setting a limit of around 3.1 x 10{sup -7} GeV{sup -1} on the coupling to photons for low mass axion-like particles. It has also been found that the parameter space of a variety of other WISP candidates is both largely unexplored and is accessible by modest experiments employing lasers and possibly accelerator magnets. GammeV data has also been used to set limits on possible hidden sector photons. Further work by the GammeV team has focused on a reconfiguration of the apparatus to be sensitive to possible chameleon particles. Chameleons are scalar (or pseudoscalar) particles that couple to the stress energy tensor in a potential such that their properties depend on their environment. In particular, a chameleon acquires an effective mass which increases with local matter density, {rho}. For a certain class of such potentials, the chameleon field has properties that might explain dark energy. GammeV set the first limits on the coupling of chameleons to photons. A dedicated follow-up experiment, GammeV-CHASE, (CHameleon

76 FR 13082 - Amendment of VOR Federal Airways V-1, V-7, V-11 and V-20; Kona, HI

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

... V-20; Kona, HI AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends four VHF Omnidirectional Range (VOR) Federal airways in the vicinity of Kona, HI; V- 1, V-7... Keahole Airport property Kailua-Kona, HI. This will enhance the management of aircraft operations over...

V and V of ISHM Software for Space Exploration

NASA Technical Reports Server (NTRS)

Markosian, Lawrence; Feather, Martin, S.; Brinza, David; Figueroa, F.

2005-01-01

NASA has established a far-reaching and long-term program for robotic and manned exploration of the solar system, beginning with missions to the moon and Mars. The Crew Transportation System (CTS), a key system for space exploration, imposes four requirements' that ISHM addresses. These requirements have a wide range of implications for V&V and certification of ISHM. There is a range of time-criticality for ISHM actions, from prognostication, which is often (but not always) non-time-critical, to time-critical state estimation and system management under off-nominal emergency conditions. These are externally imposed requirements on ISHM that are subject to V&V. - In addition, a range of techniques are needed to implement an ISHM. The approaches to ISHM are described elsewhere. These approaches range from well-understood algorithms for low-level data analysis, validation and reporting, to AI techniques for state estimation and planning. The range of techniques, and specifically the use of AI techniques such as reasoning under uncertainty and mission planning (and re-planning), implies that several V&V approaches may be required. Depending on the ISHM architecture, traditional testing approaches may be adequate for some ISHM functionality. The AI-based approaches to reasoning under uncertainty, model-based reasoning, and planning share characteristics typical of other complex software systems, but they also have characteristics that set them apart and challenge standard V&V techniques. The range of possible solutions to the overall ISHM problem impose internal challenges to V&V. The V&V challenges increase when hard real-time constraints are imposed for time-critical functionality. For example, there is an external requirement that impending catastrophic failure of the Launch Vehicle (LV) at launch time be detected and life-saving action be taken within two seconds. In this paper we outline the challenges for ISHM V&V, existing approaches and analogs in other software

New V and V Tools for Diagnostic Modeling Environment (DME)

NASA Technical Reports Server (NTRS)

Pecheur, Charles; Nelson, Stacy; Merriam, Marshall (Technical Monitor)

2002-01-01

The purpose of this report is to provide correctness and reliability criteria for verification and validation (V&V) of Second Generation Reusable Launch Vehicle (RLV) Diagnostic Modeling Environment, describe current NASA Ames Research Center tools for V&V of Model Based Reasoning systems, and discuss the applicability of Advanced V&V to DME. This report is divided into the following three sections: (1) correctness and reliability criteria; (2) tools for V&V of Model Based Reasoning; and (3) advanced V&V applicable to DME. The Executive Summary includes an overview of the main points from each section. Supporting details, diagrams, figures, and other information are included in subsequent sections. A glossary, acronym list, appendices, and references are included at the end of this report.

Dedifferentiated liposarcoma of the spermatic cord: a series of 42 cases.

PubMed

Kryvenko, Oleksandr N; Rosenberg, Andrew E; Jorda, Merce; Epstein, Jonathan I

2015-09-01

Dedifferentiated liposarcoma (DDL) of the spermatic cord is rare, with limited data regarding morphology and prognosis. We analyzed the morphologic spectrum of DDL of the spermatic cord and its clinical significance in 42 patients from 1990 to 2014. The median age of the patients was 70.5 years (range: 43 to 90 y). The median tumor size was 10.9 cm (range: 3 to 30 cm). Six cases were low-grade DDL, 28 were high-grade DDL, and in 8 cases both coexisted. Five cases had osteosarcoma, and 2 had leiomyosarcoma differentiation. Low-grade DDL had a fibrosarcoma-like (n=11), myxofibrosarcoma-like (n=2), and fibrosarcoma and inflammatory-like (n=1) pattern. High-grade DDL had a fibrosarcoma-like (n=22), undifferentiated pleomorphic sarcoma-like (n=7), myxofibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=4), fibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=2), and myxofibrosarcoma-like (n=1) pattern. Resection margins were positive in 22, negative in 13, and unknown in 7 cases. MDM2 was positive in 24/24 cases. Two patients received neoadjuvant radiotherapy (1 with chemotherapy). Patients received postoperative radiation (n=13), reexcision (n=5) with radiation (n=3), chemotherapy (n=2), chemotherapy and radiation (n=1), no therapy (n=11), and unknown (n=6). Follow-up information was available in 31 patients (mean: 54.2 mo; median: 38.5 mo; range: 2 to 180 mo). Seven patients developed local recurrence. Two patients had systemic metastases and succumbed to disease. Recurrence developed at an average of 40.9 months (median: 24 mo; range: 12 to 100 mo) after resection. Average follow-up in patients without recurrence was 45.2 months (median: 25 mo; range: 2 to 180 mo) (P=0.87). Margin status, size, and grade did not correlate with recurrence (P>0.05). Thus, DDL of the spermatic cord includes a spectrum of morphologic patterns. Complete excision is difficult at first attempt. Local recurrence is common, and relatively few patients develop systemic

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendrick, M.J.; Goldschmidt, M.H.; Shofer, F.S.

1992-10-01

An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania area appears to be related to the increased vaccination of cats following enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas arose in sites routinely used by veterinarians for vaccination, and 42 of 198 tumors were surrounded by lymphocytes and macrophages containing foreign material identical to that previously described in postvaccinal inflammatory injection site reactions. Some of the vaccines used have aluminum-based adjuvants, and macrophages surrounding three tumors contained aluminum oxide identified by electron probe microanalysis and imaged by energy-filtered electron microscopy. Persistence of inflammatorymore » and immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue repair response, leading to neoplasia.« less

An Approach to V&V of Embedded Adaptive Systems

NASA Technical Reports Server (NTRS)

Liu, Yan; Yerramalla, Sampath; Fuller, Edgar; Cukic, Bojan; Gururajan, Srikaruth

2004-01-01

Rigorous Verification and Validation (V&V) techniques are essential for high assurance systems. Lately, the performance of some of these systems is enhanced by embedded adaptive components in order to cope with environmental changes. Although the ability of adapting is appealing, it actually poses a problem in terms of V&V. Since uncertainties induced by environmental changes have a significant impact on system behavior, the applicability of conventional V&V techniques is limited. In safety-critical applications such as flight control system, the mechanisms of change must be observed, diagnosed, accommodated and well understood prior to deployment. In this paper, we propose a non-conventional V&V approach suitable for online adaptive systems. We apply our approach to an intelligent flight control system that employs a particular type of Neural Networks (NN) as the adaptive learning paradigm. Presented methodology consists of a novelty detection technique and online stability monitoring tools. The novelty detection technique is based on Support Vector Data Description that detects novel (abnormal) data patterns. The Online Stability Monitoring tools based on Lyapunov's Stability Theory detect unstable learning behavior in neural networks. Cases studies based on a high fidelity simulator of NASA's Intelligent Flight Control System demonstrate a successful application of the presented V&V methodology. ,

A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations.

PubMed

Adebanjo, O A; Moonga, B S; Haddad, J G; Huang, C L; Zaidi, M

1998-08-28

Upon removal of its sialic acid or galactose residue, vitamin D-binding protein (DBP) becomes a potent macrophage-activating factor, DBP-MAF. Here we document a new function of DBP-MAF and its parent molecule, DBP, in osteoclast control. We show that all DBPs potently inhibit extracellular Ca2+ (cation) sensing at low nanomolar concentrations with the following rank order of potency: native DBP = sialidase-treated DBP > beta-galactosidase-treated DBP. This attenuation remains unaffected despite co-incubation either with the native DBP ligand, 1,25-dihydroxyvitamin D3, or with an asialoglycoprotein receptor modulator, asialoorosomucoid. Taken together, the results suggest that circulating DBP may play a role in the systemic control of osteoclastic bone resorption, a hitherto unrecognized action of the protein.

Dlx1&2-Dependent Expression of Zfhx1b (Sip1, Zeb2) Regulates the Fate Switch Between Cortical and Striatal Interneurons

PubMed Central

McKinsey, Gabriel L.; Lindtner, Susan; Trzcinski, Brett; Visel, Axel; Pennacchio, Len A.; Huylebroeck, Danny; Higashi, Yujiro; Rubenstein, John L. R.

2013-01-01

Summary Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome). PMID:23312518

The Application of V&V within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward

1996-01-01

Verification and Validation (V&V) is performed during application development for many systems, especially safety-critical and mission-critical systems. The V&V process is intended to discover errors as early as possible during the development process. Early discovery is important in order to minimize the cost and other impacts of correcting these errors. In reuse-based software engineering, decisions on the requirements, design and even implementation of domain assets can can be made prior to beginning development of a specific system. in order to bring the effectiveness of V&V to bear within reuse-based software engineering. V&V must be incorporated within the domain engineering process.

Draft genome sequence of four coccolithoviruses: Emiliania huxleyi virus EhV-88, EhV-201, EhV-207, and EhV-208.

PubMed

Nissimov, Jozef I; Worthy, Charlotte A; Rooks, Paul; Napier, Johnathan A; Kimmance, Susan A; Henn, Matthew R; Ogata, Hiroyuki; Allen, Michael J

2012-03-01

The Coccolithoviridae are a group of viruses which infect the marine coccolithophorid microalga Emiliania huxleyi. The Emiliania huxleyi viruses (known as EhVs) described herein have 160- to 180-nm diameter icosahedral structures, have genomes of approximately 400 kbp, and consist of more than 450 predicted coding sequences (CDSs). Here, we describe the genomic features of four newly sequenced coccolithoviruses (EhV-88, EhV-201, EhV-207, and EhV-208) together with their draft genome sequences and their annotations, highlighting the homology and heterogeneity of these genomes to the EhV-86 model reference genome.

Application of tetraplex PCR for detection of Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. mimicus in cockle.

PubMed

Senachai, Pachara; Chomvarin, Chariya; Namwat, Wises; Wongboot, Warawan; Wongwajana, Suwin; Tangkanakul, Waraluk

2013-03-01

A tetraplex PCR method was developed for simultaneous detection of Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. mimicus in cockle samples in comparison with conventional culture method. Specific primers targeting ompW of V. cholerae, tl of V. parahaemolyticus, hsp60 of V. vulnificus and sodB of V. mimicus were employed in the same PCR. Detection limit of the tetraplex PCR assay was 104 cfu/ml (400 cfu/PCR reaction) for pure cultures of all four species of Vibrio. In Vibrio spiked cockle samples, the limit of detection after 6 hours enrichment in alkaline peptone water was 1 cfu/10 g of cockle tissue for three Vibrio spp, except for V. mimicus that was 102 cfu/10 g of cockle tissue. When the tetraplex PCR and culture methods were applied to 100 cockle samples, V. parahaemolyticus, V. vulnificus, V. cholerae and V. mimicus were detected in 100, 98, 80 and 9% of the samples by tetraplex PCR and in 76, 42, 0 and 0% by the culture method, respectively. This developed tetraplex PCR method should be suitable for simultaneous and rapid detection of Vibrio species in food samples and for food safety assessment.

Autonomy Software: V&V Challenges and Characteristics

NASA Technical Reports Server (NTRS)

Schumann, Johann; Visser, Willem

2006-01-01

The successful operation of unmanned air vehicles requires software with a high degree of autonomy. Only if high level functions can be carried out without human control and intervention, complex missions in a changing and potentially unknown environment can be carried out successfully. Autonomy software is highly mission and safety critical: failures, caused by flaws in the software cannot only jeopardize the mission, but could also endanger human life (e.g., a crash of an UAV in a densely populated area). Due to its large size, high complexity, and use of specialized algorithms (planner, constraint-solver, etc.), autonomy software poses specific challenges for its verification, validation, and certification. -- - we have carried out a survey among researchers aid scientists at NASA to study these issues. In this paper, we will present major results of this study, discussing the broad spectrum. of notions and characteristics of autonomy software and its challenges for design and development. A main focus of this survey was to evaluate verification and validation (V&V) issues and challenges, compared to the development of "traditional" safety-critical software. We will discuss important issues in V&V of autonomous software and advanced V&V tools which can help to mitigate software risks. Results of this survey will help to identify and understand safety concerns in autonomy software and will lead to improved strategies for mitigation of these risks.

The V1V2 EOS for Detonation Products

NASA Astrophysics Data System (ADS)

Partom, Yehuda

2010-10-01

Many equations of state (EOS) for detonation products have been proposed and used. Some of them are in analytical form and some in tabular form. The most popular is the Jones-Wilkins-Lee (JWL) EOS. One of the main parameters of a product's EOS is the so-called adiabatic gamma along its main isentrope (γs). For JWL EOSs γs(V) varies in a nonmonotonic way. Going down from the CJ point along the main isentrope, it first increases to create a hump, and then, as V goes to infinity, gamma decreases to perfect gas-like behavior with gamma around 1.3. But according to Davis [1], γs(V) should decrease monotonically with V. Accordingly, in this article we investigate the following: (1) Is the hump in γs(V) necessary? and (2) Is it possible to construct a product's EOS with a monotonic γs(V) that is consistent with experimental data? We find that (1) it is possible to construct a product's EOS without a hump in γs(V); and (2) without a hump in γs(V) there are not enough degrees of freedom to reproduce cylinder test data.

Highly effective removal of mercury and lead ions from wastewater by mercaptoamine-functionalised silica-coated magnetic nano-adsorbents: Behaviours and mechanisms

NASA Astrophysics Data System (ADS)

Bao, Shuangyou; Li, Kai; Ning, Ping; Peng, Jinhui; Jin, Xu; Tang, Lihong

2017-01-01

A novel hybrid material was fabricated using mercaptoamine-functionalised silica-coated magnetic nanoparticles (MAF-SCMNPs) and was effective in the extraction and recovery of mercury and lead ions from wastewater. The properties of this new magnetic material were explored using various characterisation and analysis methods. Adsorbent amounts, pH levels and initial concentrations were optimised to improve removal efficiency. Additionally, kinetics, thermodynamics and adsorption isotherms were investigated to determine the mechanism by which the fabricated MAF-SCMNPs adsorb heavy metal ions. The results revealed that MAF-SCMNPs were acid-resistant. Sorption likely occurred by chelation through the amine group and ion exchange between heavy metal ions and thiol functional groups on the nanoadsorbent surface. The equilibrium was attained within 120 min, and the adsorption kinetics showed pseudo-second-order (R2 > 0.99). The mercury and lead adsorption isotherms were in agreement with the Freundlich model, displaying maximum adsorption capacities of 355 and 292 mg/g, respectively. The maximum adsorptions took place at pH 5-6 and 6-7 for Hg(II) and Pb(II), respectively. The maximum adsorptions were observed at 10 mg and 12 mg adsorbent quantities for Hg(II) and Pb(II), respectively. The adsorption process was endothermic and spontaneous within the temperature range of 298-318 K. This work demonstrates a unique magnetic nano-adsorbent for the removal of Hg(II) and Pb(II) from wastewater.

The Need for V&V in Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1997-01-01

V&V is currently performed during application development for many systems, especially safety-critical and mission-critical systems. The V&V process is intended to discover errors, especially errors related to entire' domain or product line rather than a critical processing, as early as possible during the development process. The system application provides the context under which the software artifacts are validated. engineering. This paper describes a framework that extends V&V from an individual application system to a product line of systems that are developed within an architecture-based software engineering environment. This framework includes the activities of traditional application-level V&V, and extends these activities into the transition between domain engineering and application engineering. The framework includes descriptions of the types of activities to be performed during each of the life-cycle phases, and provides motivation for activities.

Overproduction of geraniol by enhanced precursor supply in Saccharomyces cerevisiae.

PubMed

Liu, Jidong; Zhang, Weiping; Du, Guocheng; Chen, Jian; Zhou, Jingwen

2013-12-01

Monoterpene geraniol, a compound obtained from aromatic plants, has wide applications. In this study, geraniol was synthesized in Saccharomyces cerevisiae through the introduction of geraniol synthase. To increase geraniol production, the mevalonate pathway in S. cerevisiae was genetically manipulated to enhance the supply of geranyl diphosphate, a substrate used for the biosynthesis of geraniol. Identification and optimization of the key regulatory points in the mevalonate pathway in S. cerevisiae increased geraniol production to 36.04 mg L(-1). The results obtained revealed that the IDI1-encoded isopentenyl diphosphate isomerase is a rate-limiting enzyme in the biosynthesis of geraniol in S. cerevisiae, and overexpression of MAF1, a negative regulator in tRNA biosynthesis, is another effective method to increase geraniol production in S. cerevisiae. Copyright © 2013 Elsevier B.V. All rights reserved.

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy

PubMed Central

Tsunoda, S; Ohizumi, I; Matsui, J; Koizumi, K; Wakai, Y; Makimoto, H; Tsutsumi, Y; Utoguchi, N; Taniguchi, K; Saito, H; Harada, N; Ohsugi, Y; Mayumi, T

1999-01-01

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. © 1999 Cancer Research Campaign PMID:10584876

To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

ClinicalTrials.gov

2018-04-23

Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents.

PubMed

Sieradzka, Dominika; Power, Robert A; Freeman, Daniel; Cardno, Alastair G; Dudbridge, Frank; Ronald, Angelica

2015-09-01

Occurrence of psychotic experiences is common amongst adolescents in the general population. Twin studies suggest that a third to a half of variance in adolescent psychotic experiences is explained by genetic influences. Here we test the extent to which common genetic variants account for some of the twin-based heritability. Psychotic experiences were assessed with the Specific Psychotic Experiences Questionnaire in a community sample of 2152 16-year-olds. Self-reported measures of Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms were obtained. Estimates of SNP heritability were derived and compared to the twin heritability estimates from the same sample. Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on pruned data. The standard GREML revealed a significant SNP heritability of 20 % for Anhedonia (SE = 0.12; p < 0.046) and an estimate of 19 % for Cognitive Disorganization, which was close to significant (SE = 0.13; p < 0.059). Grandiosity and Paranoia showed modest SNP heritability estimates (17 %; SE = 0.13 and 14 %; SE = 0.13, respectively, both n.s.), and zero estimates were found for Hallucinations and Negative Symptoms. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. SNP heritability estimates from the MAF-stratified approach were mostly consistent with the standard estimates and offered additional information about the distribution of heritability across the MAF range of the SNPs. In contrast, the estimates derived from the pruned data were for the most part not consistent with the other two approaches. It is likely that the difference seen in the pruned estimates was driven by the loss of tagged causal variants, an issue

Impact of the Mycobaterium africanum West Africa 2 Lineage on TB Diagnostics in West Africa: Decreased Sensitivity of Rapid Identification Tests in The Gambia.

PubMed

Ofori-Anyinam, Boatema; Kanuteh, Fatoumatta; Agbla, Schadrac C; Adetifa, Ifedayo; Okoi, Catherine; Dolganov, Gregory; Schoolnik, Gary; Secka, Ousman; Antonio, Martin; de Jong, Bouke C; Gehre, Florian

2016-07-01

MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37°C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs.

Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls.

PubMed

Pettersson, S; Boström, C; Eriksson, K; Svenungsson, E; Gunnarsson, I; Henriksson, E Welin

2015-08-01

The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression. Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale. Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week. Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored. © The Author(s) 2015.

Compensatory Response by Late Embryonic Tubular Epithelium to the Reduction in Pancreatic Progenitors

PubMed Central

Nishimura, Wataru; Kapoor, Archana; El Khattabi, Ilham; Jin, Wanzhu; Yasuda, Kazuki; Bonner-Weir, Susan; Sharma, Arun

2015-01-01

Early in pancreatic development, epithelial cells of pancreatic buds function as primary multipotent progenitor cells (1°MPC) that specify all three pancreatic cell lineages, i.e., endocrine, acinar and duct. Bipotent "Trunk" progenitors derived from 1°MPC are implicated in directly regulating the specification of endocrine progenitors. It is unclear if this specification process is initiated in the 1°MPC where some 1°MPC become competent for later specification of endocrine progenitors. Previously we reported that in Pdx1 tTA/+ ;tetO MafA (bigenic) mice inducing expression of transcription factor MafA in Pdx1-expressing (Pdx1+) cells throughout embryonic development inhibited the proliferation and differentiation of 1°MPC cells, resulting in reduced pancreatic mass and endocrine cells by embryonic day (E) 17.5. Induction of the transgene only until E12.5 in Pdx1+ 1°MPC was sufficient for this inhibition of endocrine cells and pancreatic mass at E17.5. However, by birth (P0), as we now report, such bigenic pups had significantly increased pancreatic and endocrine volumes with endocrine clusters containing all pancreatic endocrine cell types. The increase in endocrine cells resulted from a higher proliferation of tubular epithelial cells expressing the progenitor marker Glut2 in E17.5 bigenic embryos and increased number of Neurog3-expressing cells at E19.5. A BrdU-labeling study demonstrated that inhibiting proliferation of 1°MPC by forced MafA-expression did not lead to retention of those progenitors in E17.5 tubular epithelium. Our data suggest that the forced MafA expression in the 1°MPC inhibits their competency to specify endocrine progenitors only until E17.5, and after that compensatory proliferation of tubular epithelium gives rise to a distinct pool of endocrine progenitors. Thus, these bigenic mice provide a novel way to characterize the competency of 1°MPC for their ability to specify endocrine progenitors, a critical limitation in our

75 FR 12971 - Airworthiness Directives; International Aero Engines (IAE) V2500-A1, V2522-A5, V2524-A5, V2525-D5...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

... could result in an uncontained failure of the high-pressure (HP) compressor stage 3-8 drum and..., V2527M-A5, V2528-D5, V2530-A5, and V2533-A5 turbofan engines with high-pressure (HP) compressor stage 3-8...

Knowledge-based system V and V in the Space Station Freedom program

NASA Technical Reports Server (NTRS)

Kelley, Keith; Hamilton, David; Culbert, Chris

1992-01-01

Knowledge Based Systems (KBS's) are expected to be heavily used in the Space Station Freedom Program (SSFP). Although SSFP Verification and Validation (V&V) requirements are based on the latest state-of-the-practice in software engineering technology, they may be insufficient for Knowledge Based Systems (KBS's); it is widely stated that there are differences in both approach and execution between KBS V&V and conventional software V&V. In order to better understand this issue, we have surveyed and/or interviewed developers from sixty expert system projects in order to understand the differences and difficulties in KBS V&V. We have used this survey results to analyze the SSFP V&V requirements for conventional software in order to determine which specific requirements are inappropriate for KBS V&V and why they are inappropriate. Further work will result in a set of recommendations that can be used either as guidelines for applying conventional software V&V requirements to KBS's or as modifications to extend the existing SSFP conventional software V&V requirements to include KBS requirements. The results of this work are significant to many projects, in addition to SSFP, which will involve KBS's.

The Morelia-Acambay Fault System

NASA Astrophysics Data System (ADS)

Velázquez Bucio, M.; Soria-Caballero, D.; Garduño-Monroy, V.; Mennella, L.

2013-05-01

The Trans-Mexican Volcanic Belt (TMVB) is one of the most actives and representative zones of Mexico geologically speaking. Research carried out in this area gives stratigraphic, seismologic and historical evidence of its recent activity during the quaternary (Martinez and Nieto, 1990). Specifically the Morelia-Acambay faults system (MAFS) consist in a series of normal faults of dominant direction E - W, ENE - WSW y NE - SW which is cut in center west of the Trans-Mexican Volcanic Belt. This fault system appeared during the early Miocene although the north-south oriented structures are older and have been related to the activity of the tectonism inherited from the "Basin and Range" system, but that were reactivated by the east- west faults. It is believed that the activity of these faults has contributed to the creation and evolution of the longed lacustrine depressions such as: Chapala, Zacapu, Cuitzeo, Maravatio y Acambay also the location of monogenetic volcanoes that conformed the Michoacan-Guanajuato volcanic field (MGVF) and tend to align in the direction of the SFMA dominant effort. In a historical time different segments of the MAFS have been the epicenter of earthquakes from moderated to strong magnitude like the events of 1858 in Patzcuaro, Acambay in 1912, 1979 in Maravatio and 2007 in Morelia, among others. Several detailed analysis and semi-detailed analysis through a GIS platform based in the vectorial archives and thematic charts 1:50 000 scaled from the data base of the INEGI which has allowed to remark the influence of the MAFS segments about the morphology of the landscape and the identification of other structures related to the movement of the existent faults like fractures, alignments, collapses and others from the zone comprehended by the northwest of Morelia in Michoacán to the East of Acambay, Estado de México. Such analysis suggests that the fault segments possess a normal displacement plus a left component. In addition it can be

76 FR 72093 - Amendment of VOR Federal Airways V-81, V-89, and V-169 in the Vicinity of Chadron, NE

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

...-1016; Airspace Docket No. 11-ACE-6] RIN 2120-AA66 Amendment of VOR Federal Airways V-81, V-89, and V... airways V-81, V-89, and V-169 in the vicinity of Chadron, Nebraska. The FAA is taking this action because the Chadron VOR distance measuring equipment (DME), included as part of the V-81, V-89, and V-169...

The Role of Independent V&V in Upstream Software Development Processes

NASA Technical Reports Server (NTRS)

Easterbrook, Steve

1996-01-01

This paper describes the role of Verification and Validation (V&V) during the requirements and high level design processes, and in particular the role of Independent V&V (IV&V). The job of IV&V during these phases is to ensure that the requirements are complete, consistent and valid, and to ensure that the high level design meets the requirements. This contrasts with the role of Quality Assurance (QA), which ensures that appropriate standards and process models are defined and applied. This paper describes the current state of practice for IV&V, concentrating on the process model used in NASA projects. We describe a case study, showing the processes by which problem reporting and tracking takes place, and how IV&V feeds into decision making by the development team. We then describe the problems faced in implementing IV&V. We conclude that despite a well defined process model, and tools to support it, IV&V is still beset by communication and coordination problems.

A Framework for Performing V&V within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1996-01-01

Verification and validation (V&V) is performed during application development for many systems, especially safety-critical and mission-critical systems. The V&V process is intended to discover errors, especially errors related to critical processing, as early as possible during the development process. Early discovery is important in order to minimize the cost and other impacts of correcting these errors. In order to provide early detection of errors, V&V is conducted in parallel with system development, often beginning with the concept phase. In reuse-based software engineering, however, decisions on the requirements, design and even implementation of domain assets can be made prior to beginning development of a specific system. In this case, V&V must be performed during domain engineering in order to have an impact on system development. This paper describes a framework for performing V&V within architecture-centric, reuse-based software engineering. This framework includes the activities of traditional application-level V&V, and extends these activities into domain engineering and into the transition between domain engineering and application engineering. The framework includes descriptions of the types of activities to be performed during each of the life-cycle phases, and provides motivation for the activities.

Chain confinement, phase transitions, and lamellar structure in semicrystalline polymers, polymer blends and polymer nanocomposites

NASA Astrophysics Data System (ADS)

Chen, Huipeng

Recent studies suggest that there are three phase fractions in semicrystalline polymers, the crystalline, the mobile amorphous and the rigid amorphous phases. Due to the distinct properties of the rigid amorphous fraction, RAF, it has been investigated for more than twenty years. In this thesis, a general method using quasi-isothermal temperature-modulated differential scaning calorimetry, DSC, is provided for the first time to obtain the temperature dependent RAF and the other two fractions, crystalline fraction and mobile amorphous fraction, MAF. For poly(ethylene terephthalate), PET, our results show RAF was vitrified during quasi-isothermal cooling after crystallization had been completed and became totally devitrified during quasi-isothermal heating before the start of melting. Several years after people initially discovered the existence of RAF, another issue arose relating to the physical location of RAF and mobile amorphous fraction, MAF, within a lamellar stack model. Two very different models to describe the location of RAF were proposed. In the Heterogeneous Stack Model, HET, RAF is located outside the lamellar stacks. In the Homogeneous Stack Model, HSM, RAF was located inside the lamellar stacks. To determine the lamellar structure of semicrystalline polymers comprising three phase, a general method is given in this thesis by using a combination of the DSC and small angle X-ray scattering, SAXS techniques. It has been applied to Nylon 6, isotactic polystyrene, iPS, and PET. It was found for all of these materials, the HSM model is correct to describe the lamellar structure. In addition to the determination of lamellar structures, this method can also provide the exact fraction of MAF inside and outside lamellar stacks for binary polymer blends. For binary polymer blends, MAF, normally is located partially inside and partially outside the lamellar stacks. However, the quantification of the MAF inside and outside the lamellar stacks has now been provided

Crowdsourcing-Assisted Radio Environment Database for V2V Communication.

PubMed

Katagiri, Keita; Sato, Koya; Fujii, Takeo

2018-04-12

In order to realize reliable Vehicle-to-Vehicle (V2V) communication systems for autonomous driving, the recognition of radio propagation becomes an important technology. However, in the current wireless distributed network systems, it is difficult to accurately estimate the radio propagation characteristics because of the locality of the radio propagation caused by surrounding buildings and geographical features. In this paper, we propose a measurement-based radio environment database for improving the accuracy of the radio environment estimation in the V2V communication systems. The database first gathers measurement datasets of the received signal strength indicator (RSSI) related to the transmission/reception locations from V2V systems. By using the datasets, the average received power maps linked with transmitter and receiver locations are generated. We have performed measurement campaigns of V2V communications in the real environment to observe RSSI for the database construction. Our results show that the proposed method has higher accuracy of the radio propagation estimation than the conventional path loss model-based estimation.

Hydrogeologic framework and hydrologic budget components of the Columbia Plateau Regional Aquifer System, Washington, Oregon, and Idaho

USGS Publications Warehouse

Kahle, S.C.; Morgan, D.S.; Welch, W.B.; Ely, D.M.; Hinkle, S.R.; Vaccaro, J.J.; Orzol, L.L.

2011-01-01

groundwater samples indicates that groundwater in the CPRAS ranges in age from modern (10,000 years). The oldest groundwater resides in deep, downgradient locations indicating that groundwater movement and replenishment in parts of this regional aquifer system have operated on long timescales under past natural conditions, which is consistent with the length and depth of long flow paths in the system. The mean annual recharge from infiltration of precipitation for the 23-year period 1985-2007 was estimated to be 4.6 inches per year (14,980 cubic feet per second) using a polynomial regression equation based on annual precipitation and the results of recharge modeling done in the 1980s. A regional-scale hydrologic budget was developed using a monthly SOil WATer (SOWAT) Balance model to estimate irrigation-water demand, groundwater flux (recharge or discharge), direct runoff, and soil moisture within irrigated areas. Mean monthly irrigation throughout the study area peaks in July at 1.6 million acre-feet (MAF), of which 0.45 and 1.15 MAF are from groundwater and surface-water sources, respectively. Annual irrigation water use in the study area averaged 5.3 MAF during the period 1985-2007, with 1.4 MAF (or 26 percent) supplied from groundwater and 3.9 MAF supplied from surface water. Mean annual recharge from irrigation return flow in the study area was 4.2 MAF (1985-2007) with 2.1 MAF (50 percent) occurring within the predominately surface-water irrigated regions of the study area. Annual groundwater-use estimates were made for public supply, self-supplied domestic, industrial, and other uses for the period 1984 through 2009. Public supply groundwater use within the study area increased from 200,600 acre-feet per year (acre-ft/yr) in 1984 to 269,100 acre-ft/yr in 2009. Domestic self-supplied groundwater use increased from 54,580 acre-ft/yr in 1984 to 71,160 acre-ft/yr in 2009. Industrial groundwater use decreased from 53,390 acre-ft/yr in 1984 t