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Sample records for abnormal plasma cells

  1. Burden of cytogenetically abnormal plasma cells in light chain amyloidosis and their prognostic relevance.

    PubMed

    Kim, Seon Young; Im, Kyongok; Park, Si Nae; Kim, Jung-Ah; Yoon, Sung-Soo; Lee, Dong Soon

    2016-05-01

    We performed cytoplasmic fluorescence in situ hybridization assays of light chain amyloidosis (AL). In total, 234 patients were enrolled: 28 patients with AL, 24 with monoclonal gammopathy of undetermined significance (MGUS), and 182 with multiple myeloma (MM). Chromosomal abnormalities were detected in 13 of 22 (59%) AL patients without MM. All 13 patients demonstrated IGH rearrangement, and t(11;14)/IGH-CCND1 was most frequent (32%). Chromosome gain was not observed in AL patients without MM. These findings were dissimilar to findings in MGUS patients, in whom trisomy 9 was the most frequent abnormality. Of 6 AL patients with MM, 5 (83%) patients had cytogenetic abnormalities: 1q gain (4/6, 67%), gains of chromosome 9 (3/6, 50%), IGH rearrangement and RB1 (13q) deletions (2/6 each, 33%). The percentage of clonal plasma cells among total plasma cells was variable (median, 75%; range, 16-100%) for AL patients without MM, which was lower than the results for MM patients (median 100%). The overall survival of AL patients without MM was not significantly different according to the presence of cytogenetic abnormalities (P=0.510). In summary, among Korean AL patients, IGH rearrangement was the most frequent cytogenetic abnormality and cytogenetic aberration patterns differ compared with MGUS and MM patients. PMID:27015231

  2. Plasma Cell Disorders

    MedlinePlus

    ... microorganisms to which the body is exposed. In plasma cell disorders, one clone of plasma cells multiplies uncontrollably. As a result, this clone ... a light chain and heavy chain). These abnormal plasma cells and the ... produce are limited to one type, and levels of other types of antibodies ...

  3. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  4. Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

    PubMed

    Yin, Ai-hua; Peng, Chun-fang; Zhao, Xin; Caughey, Bennett A; Yang, Jie-xia; Liu, Jian; Huang, Wei-wei; Liu, Chang; Luo, Dong-hong; Liu, Hai-liang; Chen, Yang-yi; Wu, Jing; Hou, Rui; Zhang, Mindy; Ai, Michael; Zheng, Lianghong; Xue, Rachel Q; Mai, Ming-qin; Guo, Fang-fang; Qi, Yi-ming; Wang, Dong-mei; Krawczyk, Michal; Zhang, Daniel; Wang, Yu-nan; Huang, Quan-fei; Karin, Michael; Zhang, Kang

    2015-11-24

    Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer. PMID:26554006

  5. Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA

    PubMed Central

    Yin, Ai-hua; Peng, Chun-fang; Zhao, Xin; Caughey, Bennett A.; Yang, Jie-xia; Liu, Jian; Huang, Wei-wei; Liu, Chang; Luo, Dong-hong; Liu, Hai-liang; Chen, Yang-yi; Wu, Jing; Hou, Rui; Zhang, Mindy; Ai, Michael; Zheng, Lianghong; Xue, Rachel Q.; Mai, Ming-qin; Guo, Fang-fang; Qi, Yi-ming; Wang, Dong-mei; Krawczyk, Michal; Zhang, Daniel; Wang, Yu-nan; Huang, Quan-fei; Karin, Michael; Zhang, Kang

    2015-01-01

    Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer. PMID:26554006

  6. Plasma concentrations of endothelin in patients with abnormal vascular reactivity

    SciTech Connect

    Predel, H.G.; Meyer-Lehnert, H.; Baecker, A.; Stelkens, H.; Kramer, H.J. )

    1990-01-01

    We measured circulating concentrations of endothelin in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radioimmunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects, in patients with diabetes mellitus type I, in patients with mild to moderate essential hypertension and in non-dialyzed patients with stable chronic renal failure. Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0{plus minus}0.6 pg/ml, 4.7{plus minus}0.2 pg/ml and 6.5{plus minus}1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6{plus minus}2.9 pg/ml. No correlations were observed between serum creatinine concentrations ranging from 124 to 850 {mu}mol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin.

  7. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

    PubMed Central

    Owen, J S; Brown, D J; Harry, D S; McIntyre, N; Beaven, G H; Isenberg, H; Gratzer, W B

    1985-01-01

    Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes) were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to approximately 5,000 sites per normal erythrocyte with an association constant of 10(8) M-1. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules. Images PMID:4077979

  8. Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities

    PubMed Central

    Zhang, Alice Yang; Mysore, Naveen; Vali, Hojatollah; Koenekoop, Jamie; Cao, Sang Ni; Li, Shen; Ren, Huanan; Keser, Vafa; Lopez-Solache, Irma; Siddiqui, Sorath Noorani; Khan, Ayesha; Mui, Jeannie; Sears, Kelly; Dixon, Jim; Schwartzentruber, Jeremy; Majewski, Jacek; Braverman, Nancy; Koenekoop, Robert K.

    2015-01-01

    Purpose Photoreceptor neuronal degenerations are common, incurable causes of human blindness affecting 1 in 2000 patients worldwide. Only half of all patients are associated with known mutations in over 250 disease genes, prompting our research program to identify the remaining new genes. Most retinal degenerations are restricted to the retina, but photoreceptor degenerations can also be found in a wide variety of systemic diseases. We identified an X-linked family from Sri Lanka with a severe choroidal degeneration and postulated a new disease entity. Because of phenotypic overlaps with Bietti's crystalline dystrophy, which was recently found to have systemic features, we hypothesized that a systemic disease may be present in this new disease as well. Methods For phenotyping, we performed detailed eye exams with in vivo retinal imaging by optical coherence tomography. For genotyping, we performed whole exome sequencing, followed by Sanger sequencing confirmations and cosegregation. Systemic investigations included electron microscopy studies of peripheral blood cells in patients and in normal controls and detailed fatty acid profiles (both plasma and red blood cell [RBC] membranes). Fatty acid levels were compared to normal controls, and only values two standard deviations above or below normal controls were further evaluated. Results The family segregated a REP1 mutation, suggesting choroideremia (CHM). We then found crystals in peripheral blood lymphocytes and discovered significant plasma fatty acid abnormalities and RBC membrane abnormalities (i.e., elevated plasmalogens). To replicate our discoveries, we expanded the cohort to nine CHM patients, genotyped them for REP1 mutations, and found the same abnormalities (crystals and fatty acid abnormalities) in all patients. Conclusions Previously, CHM was thought to be restricted to the retina. We show, to our knowledge for the first time, that CHM is a systemic condition with prominent crystals in lymphocytes and

  9. "Angular" plasma cell cheilitis.

    PubMed

    da Cunha Filho, Roberto Rheingantz; Tochetto, Lucas Baldissera; Tochetto, Bruno Baldissera; de Almeida, Hiram Larangeira; Lorencette, Nádia Aparecida; Netto, José Fillus

    2014-03-01

    Plasma cell cheilitis is an extremely rare disease, characterized by erythematous-violaceous, ulcerated and asymptomatic plaques, which evolve slowly. The histological characteristics include dermal infiltrate composed of mature plasmocytes. We report a case of Plasma cell angular cheilitis in a 58-year-old male, localized in the lateral oral commissure. PMID:24656273

  10. Morphological and functional platelet abnormalities in Berkeley sickle cell mice.

    PubMed

    Shet, Arun S; Hoffmann, Thomas J; Jirouskova, Marketa; Janczak, Christin A; Stevens, Jacqueline R M; Adamson, Adewole; Mohandas, Narla; Manci, Elizabeth A; Cynober, Therese; Coller, Barry S

    2008-01-01

    Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37+/-3.2 vs. 27+/-1.4, mean+/-SD; p<0.001), in association with moderate thrombocytopenia (505+/-49 x 10(3)/microl vs. 1151+/-162 x 10(3)/microl; p<0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p<0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5+/-1% vs. 1+/-1%; p<0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease. PMID:18374611

  11. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

    PubMed

    Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

    2015-06-30

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  12. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  13. Visualizing how cancer chromosome abnormalities form in living cells

    Cancer.gov

    For the first time, scientists have directly observed events that lead to the formation of a chromosome abnormality that is often found in cancer cells. The abnormality, called a translocation, occurs when part of a chromosome breaks off and becomes attac

  14. Cell cycle regulators and their abnormalities in breast cancer.

    PubMed Central

    Fernández, P L; Jares, P; Rey, M J; Campo, E; Cardesa, A

    1998-01-01

    One of the main properties of cancer cells is their increased and deregulated proliferative activity. It is now well known that abnormalities in many positive and negative modulators of the cell cycle are frequent in many cancer types, including breast carcinomas. Abnormalities such as defective function of the retinoblastoma gene and cyclin-dependent kinase inhibitors (for example, p16, p21, and p27), as well as upregulation of cyclins, are often seen in breast tumours. These abnormalities are sometimes coincidental, and newly described interplays between them suggest the existence of a complex regulatory web in the cell cycle. PMID:10193510

  15. The effect of abnormal cell proportion on specimen classifier performance

    NASA Technical Reports Server (NTRS)

    Castleman, K. R.; White, B. S.

    1981-01-01

    An analysis is presented of the results obtained from a cell classifier which is confronted with an abnormal/normal cell ratio which is different from the ratio assumed in the calibration of the classifier. False negative and false positive error rates are determined in advance for classifier operation, along with the necessary sample size in order to validate the predicted distributions. Changes are demonstrated to happen only regarding the false negative rate, where reductions in the abnormal cell rate below the expected rates would cause totally unreliable data. Substantial overproduction of abnormal cells would be quickly noticeable, while production rates beyond, but close to, the expected rates would only require more extensive sampling. Classifier systems for 10% proportions of abnormal cells are concluded to be possible, but difficulties are present with much lower rates

  16. Plasma transfusions prior to insertion of central lines for patients with abnormal coagulation

    PubMed Central

    Hall, David P; Estcourt, Lise J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Walsh, Timothy S

    2015-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effect of different prophylactic plasma transfusion regimens prior to central line insertion in patients with abnormal coagulation. PMID:27057149

  17. Plasma cell gingivitis

    PubMed Central

    Joshi, Chandershekhar; Shukla, Pradeep

    2015-01-01

    The aim of the article is to present a report on the clinical presentation of plasma cell gingivitis with the use of herbal toothpowder. Plasma cell gingivitis [PCG] is a rare benign condition of the gingiva characterized by sharply demarcated erythematous and edematous gingivitis often extending to the mucogingival junction. As the name suggests it is diffuse and massive infiltration of plasma cells into the sub-epithelial gingival tissue. It is a hypersensitivity reaction to some antigen, often flavouring agents or spices found in chewing gums, toothpastes and lorenzes. A 27-yr old male with a chief complaint of painful, bleeding swollen mass in his lower front teeth region with prolong use of herbal toothpowder. The gingiva bled readily on probing. Patient was advised to refrain from the use of herbal toothpowder and along with periodontal treatment, no further reoccurrence was found. as more and more herbal products are gaining popularity, clinicians should be aware of effects of these products. Early diagnosis is essential as plasma cell gingivitis has similar pathologic changes seen clinically as in leukemia, HIV infection, discoid lupus erythematosis, atrophic lichen planus, desquamative gingivitis, or cicatrical pemphigoid which must be differentiated through hematologic and serologic testing. PMID:26015677

  18. Quantifying the abnormal hemodynamics of sickle cell anemia

    NASA Astrophysics Data System (ADS)

    Lei, Huan; Karniadakis, George

    2012-02-01

    Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

  19. PLASMA CELL LEUKEMIA

    PubMed Central

    de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

    2014-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

  20. Plasma cell vulvitis

    PubMed Central

    Bharatia, Pravin R.; Pradhan, Avinash M.; Zawar, Vijay P.

    2015-01-01

    Plasma cell vulvitis is a very rare inflammatory disorder of vulva, characterized by a bright-red mucosal lesion of significant chronicity, which may be symptomatic. Very few case studies of this condition are reported in literature. We describe one such classical patient, who presented with slight dyspareunia. The diagnosis was confirmed on histopathological examination. It is important for clinicians to accurately diagnose this alarming condition in time. PMID:26692614

  1. High incidence of MYC and BCL2 abnormalities in mantle cell lymphoma, although only MYC abnormality predicts poor survival

    PubMed Central

    Li, Chengwen; Zhong, Shizhen; Chen, Weiwei; Li, Zengjun; Xiong, Wenjie; Liu, Wei; Liu, Enbin; Cui, Rui; Ru, Kun; Zhang, Peihong; Xu, Yan; An, Gang; Lv, Rui; Qi, Junyuan; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2015-01-01

    The incidence and prognostic role of MYC and BCL2 rearrangements in mature B-cell lymphomas have been extensively studied, except the infrequent mantle cell lymphoma (MCL). Here, we analyzed the MYC and BCL2 abnormalities and other cytogenetic aberrations by fluorescence in situ hybridization (FISH) in 50 MCL patients with bone marrow involvement. Eighteen patients (36.0%) had MYC gains and/or amplifications, and twelve patients (24.0%) had BCL2 gains and/or amplifications. Among the 18 patients with MYC abnormality, four had simultaneous MYC translocations, but no BCL2 translocation was detected among patients with BCL2 abnormality. Only two patients (4.0%) had both MYC and BCL2 abnormalities. The patients with a MYC abnormality had a significantly higher tumor burden, a higher percentage of medium/high risk MIPI group and genomic instability compared to those without this abnormality. However, no significant difference was observed between patients with or without a BCL2 abnormality in terms of clinical and cytogenetic factors. Patients with a MYC abnormality had poorer progress-free survival (PFS) (9.0 vs. 48.0 months, p = .000) and overall survival (OS) (12.0 vs. 94.5 months, p = .000), but the presence of a BCL2 abnormality did not significantly influence either PFS or OS. In multivariate analysis, the MYC abnormality was the independent adverse factor for both PFS and OS, and intensive chemotherapy did not improve the outcome of these patients. Thus, the presence of a MYC but not BCL2 abnormality predicted the poor survival of MCL patients, and a new treatment strategy should be developed for these patients. PMID:26517511

  2. Plasma cell leukemia

    PubMed Central

    Albarracin, Flavio; Fonseca, Rafael

    2014-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

  3. ETOPOSIDE INDUCES CHROMOSOMAL ABNORMALITIES IN SPERMATOCYTES AND SPERMATOGONIAL STEM CELLS

    SciTech Connect

    Marchetti, F; Pearson, F S; Bishop, J B; Wyrobek, A J

    2005-07-15

    Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukemia, lymphomas and many solid tumors, such as testicular and ovarian cancers, that affect patients in their reproductive years. The purpose of the study was to use sperm FISH analyses to characterize the long-term effects of ET on male germ cells. We used a mouse model to characterize the induction of chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. ET treatment resulted in major increases in the frequencies of sperm carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. These results demonstrate that male meiotic germ cells are considerably more sensitive to ET than spermatogonial stem-cell and that increased frequencies of sperm with structural aberrations persist after spermatogonial stem-cell treatment. These findings predict that patients who undergo chemotherapy with ET may have transient elevations in the frequencies of aneuploid sperm, but more importantly, may have persistent elevations in the frequencies of sperm with chromosomal aberrations, placing them at higher risk for abnormal reproductive outcomes long after the end of their chemotherapy.

  4. Abnormally high expression of proteasomes in human leukemic cells.

    PubMed Central

    Kumatori, A; Tanaka, K; Inamura, N; Sone, S; Ogura, T; Matsumoto, T; Tachikawa, T; Shin, S; Ichihara, A

    1990-01-01

    Proteasomes are eukaryotic ring-shaped or cylindrical particles with multicatalytic protease activities. To clarify the involvement of proteasomes in tumorigenesis of human blood cells, we compared their expression in human hematopoietic malignant tumor cells with that in normal peripheral blood mononuclear cells. Immunohistochemical staining showed considerably increased concentrations of proteasomes in leukemic cells from the bone marrow of patients with various types of leukemia and the predominant localization of these proteasomes in the nuclei. Moreover, enzyme immunoassay and Northern blot analysis indicated that the concentrations of proteasomes and their mRNA levels were consistently much higher in a variety of malignant human hematopoietic cell lines than in resting peripheral lymphocytes and monocytes from healthy adults. Proteasome expression was also greatly increased in normal blood mononuclear cells during blastogenic transformation induced by phytohemagglutinin; their expression increased in parallel with induction of DNA synthesis and returned to the basal level with progress of the cell cycle. Thus, abnormally high expression of proteasomes may play an important role in transformation and proliferation of blood cells and in specific functions of hematopoietic tumor cells. Images PMID:2205851

  5. Abnormal neutrophil adhesion in sickle cell anaemia and crisis: relationship to blood rheology.

    PubMed

    Boghossian, S H; Nash, G; Dormandy, J; Bevan, D H

    1991-07-01

    Defects in neutrophil adhesion and migration may contribute to the susceptibility to infection seen in sickle cell anaemia (SCA). These dynamic defects may be influenced by abnormalities in blood rheology found in this disorder. A whole blood model was used to study neutrophil adhesion in SCA patients: neutrophil adhesion to protein coated glass was quantitated by measuring the rate of disappearance of neutrophils from heparinized whole blood circulating through a perfusion chamber. Twenty-three adult patients (Hb SS) were studied in asymptomatic steady state, of whom nine were also studied during pain crisis, both before and 4-7 d after conventional therapy. Red cell and granulocyte filterability and whole blood and plasma viscosity were also measured. The half-time for disappearance from the perfusion system (t1/2) of neutrophils from patients in the steady-state was 93.5 +/- 8.4 min, compared to 49.1 +/- 2.8 min in normal age-matched controls (P = 0.001). In crisis t1/2 was further prolonged to 170.0 +/- 16.1 min (P = 0.01 v. steady state). After therapy, t1/2 decreased to 57.0 +/- 4.5 min (P = 0.001 v. pre-therapy state and P = 0.009 v. steady state) and was comparable to Hb AA controls. These findings reveal a neutrophil adhesion defect in SCA which worsens in crisis but is corrected following supportive therapy. Red cell filterability (expressed as average resistance to flow and pore-clogging particles) and white cell filterability (expressed as pore-clogging particles) were also abnormal in SCA and were found to correlate with neutrophil adhesion. Plasma viscosity also correlated with adhesion t1/2. The defect appears to be related to abnormal blood flow properties in SCA but the rheological factors cannot fully explain either the steady-state defect or the marked changes in neutrophil adhesion during crisis. PMID:1873228

  6. Closed inductively coupled plasma cell

    DOEpatents

    Manning, T.J.; Palmer, B.A.; Hof, D.E.

    1990-11-06

    A closed inductively coupled plasma cell generates a relatively high power, low noise plasma for use in spectroscopic studies is disclosed. A variety of gases can be selected to form the plasma to minimize spectroscopic interference and to provide a electron density and temperature range for the sample to be analyzed. Grounded conductors are placed at the tube ends and axially displaced from the inductive coil, whereby the resulting electromagnetic field acts to elongate the plasma in the tube. Sample materials can be injected in the plasma to be excited for spectroscopy. 1 fig.

  7. Closed inductively coupled plasma cell

    DOEpatents

    Manning, Thomas J.; Palmer, Byron A.; Hof, Douglas E.

    1990-01-01

    A closed inductively coupled plasma cell generates a relatively high power, low noise plasma for use in spectroscopic studies. A variety of gases can be selected to form the plasma to minimize spectroscopic interference and to provide a electron density and temperature range for the sample to be analyzed. Grounded conductors are placed at the tube ends and axially displaced from the inductive coil, whereby the resulting electromagnetic field acts to elongate the plasma in the tube. Sample materials can be injected in the plasma to be excited for spectroscopy.

  8. Plasma Etching Improves Solar Cells

    NASA Technical Reports Server (NTRS)

    Bunyan, S. M.

    1982-01-01

    Etching front surfaces of screen-printed silicon photovoltaic cells with sulfur hexafluoride plasma found to increase cell performance while maintaining integrity of screen-printed silver contacts. Replacement of evaporated-metal contacts with screen-printed metal contacts proposed as one way to reduce cost of solar cells for terrestrial applications.

  9. How I treat plasma cell leukemia

    PubMed Central

    Lokhorst, Henk M.; Anderson, Kenneth C.; Richardson, Paul G.

    2012-01-01

    Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum β2-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients. PMID:22837533

  10. How I treat plasma cell leukemia.

    PubMed

    van de Donk, Niels W C J; Lokhorst, Henk M; Anderson, Kenneth C; Richardson, Paul G

    2012-09-20

    Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum β(2)-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients. PMID:22837533

  11. Real-Time Plasma Process Condition Sensing and Abnormal Process Detection

    PubMed Central

    Yang, Ryan; Chen, Rongshun

    2010-01-01

    The plasma process is often used in the fabrication of semiconductor wafers. However, due to the lack of real-time etching control, this may result in some unacceptable process performances and thus leads to significant waste and lower wafer yield. In order to maximize the product wafer yield, a timely and accurately process fault or abnormal detection in a plasma reactor is needed. Optical emission spectroscopy (OES) is one of the most frequently used metrologies in in-situ process monitoring. Even though OES has the advantage of non-invasiveness, it is required to provide a huge amount of information. As a result, the data analysis of OES becomes a big challenge. To accomplish real-time detection, this work employed the sigma matching method technique, which is the time series of OES full spectrum intensity. First, the response model of a healthy plasma spectrum was developed. Then, we defined a matching rate as an indictor for comparing the difference between the tested wafers response and the health sigma model. The experimental results showed that this proposal method can detect process faults in real-time, even in plasma etching tools. PMID:22219683

  12. Abnormalities of plasma cytokines and spleen in senile APP/PS1/Tau transgenic mouse model

    PubMed Central

    Yang, Seung-Hoon; Kim, Jiyoon; Lee, Michael Jisoo; Kim, YoungSoo

    2015-01-01

    The blood-based diagnosis has a potential to provide an alternative approach for easy diagnosis of Alzheimer’s disease (AD) with less invasiveness and low-cost. However, present blood-based AD diagnosis mainly focuses on measuring the plasma Aβ level because no other biomarkers are found to possess evident transport mechanisms to pass the blood-brain barrier. In order to avoid diagnosing non-demented individuals with Aβ abnormality, finding additional biomarkers to supplement plasma Aβ is essential. In this study, we introduce potential neurodegenerative biomarkers for blood-based diagnosis. We observed severe splenomegaly and structural destruction in the spleen with significantly decreased B lymphocytes in senile APPswe, PS1M146V and TauP301L transgenic mice. We also found that inflammatory cytokines associated with splenic dysfunction were altered in the plasma of these mice. These findings suggest potential involvement of the splenic dysfunction in AD and the importance of biomarker level alterations in the plasma as putative diagnostic targets for AD. PMID:26503550

  13. Normal and abnormal evolution of argon metastable density in high-density plasmas

    SciTech Connect

    Seo, B. H.; Kim, J. H.; You, S. J.

    2015-05-15

    A controversial problem on the evolution of Ar metastable density as a function of electron density (increasing trend versus decreasing trend) was resolved by discovering the anomalous evolution of the argon metastable density with increasing electron density (discharge power), including both trends of the metastable density [Daltrini et al., Appl. Phys. Lett. 92, 061504 (2008)]. Later, by virtue of an adequate physical explanation based on a simple global model, both evolutions of the metastable density were comprehensively understood as part of the abnormal evolution occurring at low- and high-density regimes, respectively, and thus the physics behind the metastable evolution has seemed to be clearly disclosed. In this study, however, a remarkable result for the metastable density behavior with increasing electron density was observed: even in the same electron density regime, there are both normal and abnormal evolutions of metastable-state density with electron density depending on the measurement position: The metastable density increases with increasing electron density at a position far from the inductively coupled plasma antenna but decreases at a position close to the antenna. The effect of electron temperature, which is spatially nonuniform in the plasma, on the electron population and depopulation processes of Argon metastable atoms with increasing electron density is a clue to understanding the results. The calculated results of the global model, including multistep ionization for the argon metastable state and measured electron temperature, are in a good agreement with the experimental results.

  14. Plasma TGF-β1 Levels Are Elevated in Down Syndrome Infants with Transient Abnormal Myelopoiesis.

    PubMed

    Maeda, Hajime; Go, Hayato; Imamura, Takashi; Sato, Maki; Momoi, Nobuo; Hosoya, Mitsuaki

    2016-01-01

    Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-β1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-β1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-β1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-β1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis. PMID:27546516

  15. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    SciTech Connect

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  16. Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells

    SciTech Connect

    Liao Weiting; Lin Pinpin; Cheng, T.-S.; Yu, H.-S.; Chang, Louis W.

    2007-12-01

    Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus, an interaction between arsenic and cigarette smoking in lung carcinogenesis was suspected. p53 dysfunction or mutation in lung epithelial cells was frequently observed in cigarette smokers. Our present study was to explore the differential effects by arsenic on H1355 cells (human lung adenocarcinoma cell line with mutation in p53), BEAS-2B (immortalized lung epithelial cell with functional p53) and pifithrin-{alpha}-treated BEAS-2B cells (p53-inhibited cells). These cells were treated with different doses of sodium arsenite (0, 0.1, 1, 5 and 10 {mu}M) for 48 h. A greater reduction in cell viability was observed in the BEAS-2B cells vs. p53 compromised cells (H1355 or p53-inhibited BEAS-2B). Similar observation was also made on 7-day cell survival (growth) study. TUNEL analysis confirmed that there was indeed a significantly reduced arsenite-induced apoptosis found in p53-compromised cells. Centrosomal abnormality has been attributed to eventual chromosomal missegregation, aneuploidy and tumorigenesis. In our present study, reduced p21 and Gadd45a expressions and increased centrosomal abnormality (atopic and multiple centrosomes) were observed in both arsenite-treated H1355 and p53-inhibited BEAS-2B cells as compared with similarly treated BEAS-2B cells. Increased anchorage-independent growth (colony formation) of BEAS-2B cells co-treated with pifithrin-{alpha} and 5 {mu}M sodium arsenite was also observed in soft agar. Our present investigation demonstrated that arsenic would act specifically on p53 compromised cells (either with p53 dysfunction or inhibited) to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenic, especially under the condition of p53 dysfunction.

  17. Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

    PubMed

    Chang, Yao-Lung; Chao, An-Shine; Peng, Hsiu-Huei; Chang, Shuenn-Dyh; Su, Sheng-Yuan; Chen, Kuan-Ju; Cheng, Po-Jen; Wang, Tzu-Hao

    2016-08-01

    Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia. PMID:27161360

  18. Iron granules in plasma cells.

    PubMed Central

    Cook, M K; Madden, M

    1982-01-01

    The curious and unusual finding of coarse iron granules in marrow plasma cells is reported in 13 patients, in whom the finding was incidental. In 10 of these patients there was known alcohol abuse and serious medical complications of that abuse. Previous reports of the finding are reviewed. Haematological data of the 13 patients are presented. A hypothesis is outlined which may account for the finding. Images PMID:7068907

  19. Cell phone radiation effects on cytogenetic abnormalities of oral mucosal cells.

    PubMed

    Daroit, Natália Batista; Visioli, Fernanda; Magnusson, Alessandra Selinger; Vieira, Geila Radunz; Rados, Pantelis Varvaki

    2015-01-01

    The aim of this study was to evaluate the effects of exposure to cell phone electromagnetic radiation on the frequency of micronuclei, broken eggs cells, binucleated cells, and karyorrhexis in epithelial cells of the oral mucosa. The sample was composed of 60 cell phone users, who were non-smokers and non-drinkers, and had no clinically visible oral lesions. Cells were obtained from anatomical sites with the highest incidence of oral cancer: lower lip, border of the tongue, and floor of the mouth. The Feulgen reaction was used for quantification of nuclear anomalies in 1,000 cells/slide. A slightly increase in the number of micronucleated cells in the lower lip and in binucleated cells on the floor of the mouth was observed in individuals who used their phones > 60 minutes/week. The analysis also revealed an increased number of broken eggs in the tongue of individuals owning a cell phone for over eight years. Results suggest that exposure to electromagnetic waves emitted by cell phones can increase nuclear abnormalities in individuals who use a cell phone for more than 60 minutes per week and for over eight years. Based on the present findings, we suggest that exposure to electromagnetic radiation emitted by cell phones may interfere with the development of metanuclear anomalies. Therefore, it is demonstrated that, despite a significant increase in these anomalies, the radiation emitted by cell phones among frequent users is within acceptable physiological limits. PMID:26486771

  20. Nanoscale Drug Delivery Platforms Overcome Platinum-Based Resistance in Cancer Cells Due to Abnormal Membrane Protein Trafficking

    PubMed Central

    Xue, Xue; Hall, Matthew D.; Zhang, Qiang; Wang, Paul C.; Gottesman, Michael M.; Liang, Xing-Jie

    2014-01-01

    The development of cellular resistance to platinum-based chemotherapies is often associated with reduced intracellular platinum concentrations. In some models, this reduction is due to abnormal membrane protein trafficking, resulting in reduced uptake by transporters at the cell surface. Given the central role of platinum drugs in the clinic, it is critical to overcome cisplatin resistance by bypassing the plasma membrane barrier to significantly increase the intracellular cisplatin concentration enough to inhibit the proliferation of cisplatin-resistant cells. Therefore, rational design of appropriate nanoscale drug delivery platforms (nDDPs) loaded with cisplatin or other platinum analogs as payloads is a possible strategy to solve this problem. This review will focus on the known mechanism of membrane trafficking in cisplatin-resistant cells, and the development and employment of nDDPs to improve cell uptake of cisplatin. PMID:24219825

  1. Abnormal Schwann cell/axon interactions in the Trembler-J mouse

    PubMed Central

    ROBERTSON, A. M.; KING, R. H. M.; MUDDLE, J. R.; THOMAS, P. K.

    1997-01-01

    The Trembler-J (TrJ) mouse has a point mutation in the gene coding for peripheral myelin protein 22 (PMP22). Disturbances in PMP22 are associated with abnormal myelination in a range of inherited peripheral neuropathies both in mice and humans. PMP22 is produced mainly by Schwann cells in the peripheral nervous system where it is localised to compact myelin. The function of PMP22 is unclear but its low abundance (∼5% of total myelin protein) means that it is unlikely to play a structural role. Its inclusion in a recently discovered family of proteins suggests a function in cell proliferation/differentiation and possibly in adhesion. Nerves from TrJ and the allelic Trembler (Tr) mouse are characterised by abnormally thin myelin for the size of the axon and an increased number of Schwann cells. We report ultrastructural evidence of abnormal Schwann cell-axon interactions. Schwann cell nuclei have been found adjacent to the nodes of Ranvier whereas in normal animals they are located near the centre of the internodes. In some fibres the terminal myelin loops faced outwards into the extracellular space instead of turning inwards and terminating on the axon. In severely affected nerves many axons were only partially surrounded by Schwann cell cytoplasm. All these features suggest a failure of Schwann cell–axon recognition or interaction. In addition to abnormalities related to abnormal myelination there was significant axonal loss in the dorsal roots. PMID:9147228

  2. Gas Plasma Effects on Living Cells

    NASA Astrophysics Data System (ADS)

    Stoffels, E.; Sladek, R. E. J.; Kieft, I. E.

    This paper surveys the research activities at the Eindhoven University of Technology (The Netherlands) in the area of biomedical applications of gas discharge plasmas. A non-thermal atmospheric plasma source (the plasma needle) has been developed, and its interactions with living mammalian cells and bacteria are studied. It is concluded that plasma can efficiently kill bacteria without harming the cells, and also influence the cells without causing cell death (necrosis). In future it will lead to applications like skin (wound) and caries treatment.

  3. Hemorrhagic Skin Nodules and Plaques: A Diagnostic Clue to Underlying Primary Plasma Cell Leukemia

    PubMed Central

    Gupta, Ranjan; Nath, Amiya Kumar; Subbian, Murugavel; Basu, Debdatta; Hamide, Abdoul; D'Souza, Mariette

    2016-01-01

    Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells (PC) in blood and marrow. Cutaneous involvement is very rare in PCL. We present the case of a 45-year-old lady who presented with multiple hemorrhagic nodules and plaques in the skin. Her total leucocyte count was 2,00,200/cmm with 85% abnormal plasmacytoid cells in peripheral smear. Biopsy of the skin lesions revealed diffuse infiltration by plasma cells with ‘choked’ blood vessels. A diagnosis of plasma cell leukemia with cutaneous involvement was made. On the second day of admission, the patient expired probably because of intracranial bleed due to thrombocytopenia. Post-mortem bone marrow and liver biopsy also showed diffuse infiltration by plasma cells. Monoclonality of the cells was proven by demonstrating the production of only kappa light chains. PMID:27057024

  4. Hemorrhagic Skin Nodules and Plaques: A Diagnostic Clue to Underlying Primary Plasma Cell Leukemia.

    PubMed

    Gupta, Ranjan; Nath, Amiya Kumar; Subbian, Murugavel; Basu, Debdatta; Hamide, Abdoul; D'Souza, Mariette

    2016-01-01

    Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells (PC) in blood and marrow. Cutaneous involvement is very rare in PCL. We present the case of a 45-year-old lady who presented with multiple hemorrhagic nodules and plaques in the skin. Her total leucocyte count was 2,00,200/cmm with 85% abnormal plasmacytoid cells in peripheral smear. Biopsy of the skin lesions revealed diffuse infiltration by plasma cells with 'choked' blood vessels. A diagnosis of plasma cell leukemia with cutaneous involvement was made. On the second day of admission, the patient expired probably because of intracranial bleed due to thrombocytopenia. Post-mortem bone marrow and liver biopsy also showed diffuse infiltration by plasma cells. Monoclonality of the cells was proven by demonstrating the production of only kappa light chains. PMID:27057024

  5. Cell signaling abnormalities may drive neurodegeneration in familial Alzheimer disease.

    PubMed

    Robakis, Nikolaos K

    2014-01-01

    Presenilins (PSs) are catalytic components of the γ-secretase complex that produces Aβ peptides. Substrates of γ-secretase are membrane-bound protein fragments deriving from the cleavage of extracellular sequence of cell surface proteins. APP-derived γ-secretase substrates are cleaved at gamma (γ) sites to produce Aβ while cleavage at the epsilon (ε) site produces AICD proposed to function in transcription. In addition to APP, γ-secretase promotes the ε-cleavage of a large number of cell surface proteins producing cytosolic peptides shown to function in cell signaling. A common hypothesis suggests that Alzheimer's disease (AD) is caused by Aβ peptides or their products. Treatment of patients with inhibitors of Aβ production however, showed no therapeutic benefits while inducing cytotoxicity. Similarly, treatments with anti-Aβ antibodies yielded disappointing results. Importantly, recent evidence shows that PS familial AD (FAD) mutations cause a loss of γ-secretase cleavage activity at ε site of substrates thus inhibiting production of biologically important cell signaling peptides while promoting accumulation of membrane-bound cytotoxic substrates. These data support a hypothesis that FAD mutations may increase neurotoxicity by inhibiting the γ-secretase-catalyzed ε cleavage of substrates thus interfering with cell signaling while also promoting accumulation of cytotoxic peptides. Similar mechanisms may explain γ-secretase inhibitor-associated toxicities observed in clinical trials. Here we discuss evidence that FAD neurodegeneration may be caused by loss of γ-secretase cleavage function at ε sites of substrates. PMID:23436150

  6. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells

    SciTech Connect

    Aanei, Carmen Mariana; Eloae, Florin Zugun; Flandrin-Gresta, Pascale; Tavernier, Emmanuelle; Carasevici, Eugen; Guyotat, Denis; Campos, Lydia

    2011-11-01

    Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.

  7. Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis.

    PubMed

    Guerra, María Montserrat; Henzi, Roberto; Ortloff, Alexander; Lichtin, Nicole; Vío, Karin; Jiménez, Antonio J; Dominguez-Pinos, María Dolores; González, César; Jara, Maria Clara; Hinostroza, Fernando; Rodríguez, Sara; Jara, Maryoris; Ortega, Eduardo; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad E; Rodríguez, Esteban M

    2015-07-01

    Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis. We used bromodeoxyuridine labeling, immunocytochemistry, electron microscopy, and cell culture to study the telencephalon of hydrocephalic HTx rats and correlated our findings with those in human hydrocephalic and nonhydrocephalic human fetal brains (n = 12 each). Our results suggest that abnormal expression of the intercellular junction proteins N-cadherin and connexin-43 in NSC leads to 1) disruption of the ventricular and subventricular zones, loss of NSCs and neural progenitor cells; and 2) abnormalities in neurogenesis such as periventricular heterotopias and abnormal neuroblast migration. In HTx rats, the disrupted NSC and progenitor cells are shed into the cerebrospinal fluid and can be grown into neurospheres that display intercellular junction abnormalities similar to those of NSC of the disrupted ventricular zone; nevertheless, they maintain their potential for differentiating into neurons and glia. These NSCs can be used to investigate cellular and molecular mechanisms underlying this condition, thereby opening the avenue for stem cell therapy. PMID:26079447

  8. Autophagy in Plasma Cell Pathophysiology

    PubMed Central

    Oliva, Laura; Cenci, Simone

    2014-01-01

    Plasma cells (PCs) are the effectors responsible for antibody (Ab)-mediated immunity. They differentiate from B lymphocytes through a complete remodeling of their original structure and function. Stress is a constitutive element of PC differentiation. Macroautophagy, conventionally referred to as autophagy, is a conserved lysosomal recycling strategy that integrates cellular metabolism and enables adaptation to stress. In metazoa, autophagy plays diverse roles in cell differentiation. Recently, a number of autophagic functions have been recognized in innate and adaptive immunity, including clearance of intracellular pathogens, inflammasome regulation, lymphocyte ontogenesis, and antigen presentation. We identified a previously unrecognized role played by autophagy in PC differentiation and activity. Following B cell activation, autophagy moderates the expression of the transcriptional repressor Blimp-1 and immunoglobulins through a selective negative control exerted on the size of the endoplasmic reticulum and its stress signaling response, including the essential PC transcription factor, XBP-1. This containment of PC differentiation and function, i.e., Ab production, is essential to optimize energy metabolism and viability. As a result, autophagy sustains Ab responses in vivo. Moreover, autophagy is an essential intrinsic determinant of long-lived PCs in their as yet poorly understood bone marrow niche. In this essay, we discuss these findings in the context of the established biological functions of autophagy, and their manifold implications for adaptive immunity and PC diseases, in primis multiple myeloma. PMID:24659989

  9. Neoplastic development in plasma cells.

    PubMed

    Potter, Michael

    2003-08-01

    An increasing number of model systems of plasma cell tumor (PCT) formation have been and are being developed. Discussed here are six models in mice and multiple myeloma (MM) in humans. Each model illustrates a unique set of biological factors. There are two general types of model systems: those that depend upon naturally arising mutagenic changes (pristane-induced PCTs, 5TMM, and MM) and those that are associated with oncogenes (Emu-v-abl), growth factors [interleukin-6 (IL-6)], and anti-apoptotic factors (Bcl-xL/Bcl-2). PCTs develop in several special tissue microenvironments that provide essential cytokines (IL-6) and cell-cell interactions. In mice, the activation and deregulation of c-myc by chromosomal translocations is a major feature in many of the models. This mechanism is much less a factor in MM and the 5T model in mice. Genetically determined susceptibility is involved in many of the mouse models, but only a few genes have been implicated thus far. PMID:12846815

  10. A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells

    NASA Astrophysics Data System (ADS)

    Pan, Hsu-An; Hung, Yao-Ching; Su, Chia-Wei; Tai, Shih-Ming; Chen, Chiun-Hsun; Ko, Fu-Hsiang; Steve Huang, G.

    2009-08-01

    Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN) or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions.

  11. Growth and differentiation of circulating hemopoietic stem cells with atomic bomb irradiation-induced chromosome abnormalities

    SciTech Connect

    Amenomori, T.; Honda, T.; Otake, M.; Tomonaga, M.; Ichimaru, M.

    1988-11-01

    The effects of atomic bomb irradiation on hemopoietic stem cells were studied cytogenetically using single colonies derived from hemopoietic progenitor cells. The subjects studied were 21 healthy atomic bomb survivors (10 males and 11 females) in the high dose exposure group (100+ rad) with a known high incidence (10% or more) of radiation-induced chromosome abnormalities in their peripheral blood lymphocytes (stimulated with phytohemagglutinin), and 11 nonexposed healthy controls (5 males and 6 females). Colony formation by circulating granulocyte-macrophage (GM-CFC) and erythroid (BFU-E) progenitor cells was made by the methylcellulose method using peripheral blood mononuclear cells. Chromosome specimens were prepared from single colonies by our micromethod. The total number of colonies analyzed in the exposed group was 131 for GM-CFC and 75 for BFU-E. Chromosome abnormalities were observed in 15 (11.5%) and 9 (12.0%) colonies, respectively. In the control group, the total number of colonies analyzed was 61 for GM-CFC and 41 for BFU-E. None of these colonies showed chromosome abnormalities. The difference in incidence of chromosome abnormalities was highly significant by an exact test; p = 0.003 for GM-CFC and 0.017 for BFU-E. The karyotypes of chromosome abnormalities obtained from the colonies in the exposed group were mostly translocations, but deletion and marker chromosomes were also observed. In two individuals, such karyotypic abnormalities as observed in the peripheral lymphocytes were also seen in the myeloid progenitor cells. This finding suggests that atomic bomb irradiation produced a chromosome aberration on multipotent hemopoietic stem cells common to myeloid and lymphoid lineages.

  12. Accumulation of abnormal adult-generated hippocampal granule cells predicts seizure frequency and severity

    PubMed Central

    Hester, Michael S.; Danzer, Steve C.

    2013-01-01

    Accumulation of abnormally integrated, adult-born, hippocampal dentate granule cells (DGC) is hypothesized to contribute to the development of temporal lobe epilepsy (TLE). DGCs have long been implicated in TLE, as they regulate excitatory signaling through the hippocampus and exhibit neuroplastic changes during epileptogenesis. Furthermore, DGCs are unusual in that they are continually generated throughout life, with aberrant integration of new cells underlying the majority of restructuring in the dentate during epileptogenesis. While it is known that these abnormal networks promote abnormal neuronal firing and hyperexcitability, it has yet to be established whether they directly contribute to seizure generation. If abnormal DGCs do contribute, a reasonable prediction would be that the severity of epilepsy will be correlated with the number or load of abnormal DGCs. To test this prediction, we utilized a conditional, inducible transgenic mouse model to fate-map adult-generated DGCs. Mossy cell loss, also implicated in epileptogenesis, was assessed as well. Transgenic mice rendered epileptic using the pilocarpine-status epilepticus model of epilepsy were monitored 24/7 by video/EEG for four weeks to determine seizure frequency and severity. Positive correlations were found between seizure frequency and: 1) the percentage of hilar ectopic DGCs, 2) the amount of mossy fiber sprouting and 3) the extent of mossy cell death. In addition, mossy fiber sprouting and mossy cell death were correlated with seizure severity. These studies provide correlative evidence in support of the hypothesis that abnormal DGCs contribute to the development of TLE, and also support a role for mossy cell loss. PMID:23699504

  13. Clinically granulomatous cheilitis with plasma cells.

    PubMed

    Sarkar, Somenath; Ghosh, Sarmistha; Sengupta, Dipayan

    2016-01-01

    Plasma cell cheilitis, also known as plasma cell orificial mucositis is a benign inflammatory condition clinically characterized by erythematous plaque on lips that may be ulcerated. Histopathologically it is characterized by dense plasma cell infiltrates in a band-like pattern in dermis, which corresponds to Zoon's plasma cell balanitis. On the other hand, granulomatous cheilitis, as a part of orofacial granulomatosis, manifests as sudden diffuse or nodular swelling involving lip and cheek. Initial swelling is soft to firm, but with recurrent episodes swelling gradually become firm rubbery in consistency. We hereby report a case of cheilitis in a 52-year-old man with diffuse swelling involving lower lip, which clinically resembles granulomatous cheilitis, but histopathological examination showed diffuse infiltrate of plasma cells predominantly in upper and mid-dermis. PMID:27057489

  14. Clinically granulomatous cheilitis with plasma cells

    PubMed Central

    Sarkar, Somenath; Ghosh, Sarmistha; Sengupta, Dipayan

    2016-01-01

    Plasma cell cheilitis, also known as plasma cell orificial mucositis is a benign inflammatory condition clinically characterized by erythematous plaque on lips that may be ulcerated. Histopathologically it is characterized by dense plasma cell infiltrates in a band-like pattern in dermis, which corresponds to Zoon's plasma cell balanitis. On the other hand, granulomatous cheilitis, as a part of orofacial granulomatosis, manifests as sudden diffuse or nodular swelling involving lip and cheek. Initial swelling is soft to firm, but with recurrent episodes swelling gradually become firm rubbery in consistency. We hereby report a case of cheilitis in a 52-year-old man with diffuse swelling involving lower lip, which clinically resembles granulomatous cheilitis, but histopathological examination showed diffuse infiltrate of plasma cells predominantly in upper and mid-dermis. PMID:27057489

  15. Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin.

    PubMed

    Graf, R J; Halter, J B; Halar, E; Porte, D

    1979-03-01

    The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease. PMID:426398

  16. Drugs Approved for Multiple Myeloma and Other Plasma Cell Neoplasms

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Multiple Myeloma and Other Plasma Cell ... plasma cell neoplasms that are not listed here. Drugs Approved for Multiple Myeloma and Other Plasma Cell ...

  17. The development of hepatic stellate cells in normal and abnormal human fetuses – an immunohistochemical study

    PubMed Central

    Loo, Christine K C; Pereira, Tamara N; Pozniak, Katarzyna N; Ramsing, Mette; Vogel, Ida; Ramm, Grant A

    2015-01-01

    The precise embryological origin and development of hepatic stellate cells is not established. Animal studies and observations on human fetuses suggest that they derive from posterior mesodermal cells that migrate via the septum transversum and developing diaphragm to form submesothelial cells beneath the liver capsule, which give rise to mesenchymal cells including hepatic stellate cells. However, it is unclear if these are similar to hepatic stellate cells in adults or if this is the only source of stellate cells. We have studied hepatic stellate cells by immunohistochemistry, in developing human liver from autopsies of fetuses with and without malformations and growth restriction, using cellular Retinol Binding Protein-1 (cRBP-1), Glial Fibrillary Acidic Protein (GFAP), and α-Smooth Muscle Actin (αSMA) antibodies, to identify factors that influence their development. We found that hepatic stellate cells expressing cRBP-1 are present from the end of the first trimester of gestation and reduce in density throughout gestation. They appear abnormally formed and variably reduced in number in fetuses with abnormal mesothelial Wilms Tumor 1 (WT1) function, diaphragmatic hernia and in ectopic liver nodules without mesothelium. Stellate cells showed similarities to intravascular cells and their presence in a fetus with diaphragm agenesis suggests they may be derived from circulating stem cells. Our observations suggest circulating stem cells as well as mesothelium can give rise to hepatic stellate cells, and that they require normal mesothelial function for their development. PMID:26265759

  18. Relationship between pulmonary and cardiac abnormalities in sickle cell disease: implications for the management of patients

    PubMed Central

    Maioli, Maria Christina Paixão; Soares, Andrea Ribeiro; Bedirian, Ricardo; Alves, Ursula David; de Lima Marinho, Cirlene; Lopes, Agnaldo José

    2015-01-01

    Objective To evaluate the association between clinical, pulmonary, and cardiovascular findings in patients with sickle cell disease and, secondarily, to compare these findings between sickle cell anemia patients and those with other sickle cell diseases. Methods Fifty-nine adults were included in this cross-sectional study; 47 had sickle cell anemia, and 12 had other sickle cell diseases. All patients underwent pulmonary function tests, chest computed tomography, and echocardiography. Results Abnormalities on computed tomography, echocardiography, and pulmonary function tests were observed in 93.5%, 75.0%; and 70.2% of patients, respectively. A higher frequency of restrictive abnormalities was observed in patients with a history of acute chest syndrome (85% vs. 21.6%; p-value < 0.0001) and among patients with increased left ventricle size (48.2% vs. 22.2%; p-value = 0.036), and a higher frequency of reduced respiratory muscle strength was observed in patients with a ground-glass pattern (33.3% vs. 4.3%; p-value = 0.016). Moreover, a higher frequency of mosaic attenuation was observed in patients with elevated tricuspid regurgitation velocity (61.1% vs. 24%; p-value = 0.014). Compared to patients with other sickle cell diseases, sickle cell anemia patients had suffered increased frequencies of acute pain episodes, and acute chest syndrome, and exhibited mosaic attenuation on computed tomography, and abnormalities on echocardiography. Conclusion A significant interrelation between abnormalities of the pulmonary and cardiovascular systems was observed in sickle cell disease patients. Furthermore, the severity of the cardiopulmonary parameters among patients with sickle cell anemia was greater than that of patients with other sickle cell diseases. PMID:26969771

  19. Abnormal bone marrow distribution following unsuccessful hip replacement: a potential confusion on white cell scanning.

    PubMed

    Cunningham, D A

    1991-01-01

    A case is presented in which a grossly abnormal distribution of bone marrow following failed hip replacement would have led to the false diagnosis of osteomyelitis. The value of combining bone marrow scanning with indium white cell scanning in possible osteomyelitis is emphasised. PMID:2019282

  20. T-cell abnormalities in common variable immunodeficiency: the hidden defect

    PubMed Central

    Wong, Gabriel K; Huissoon, Aarnoud P

    2016-01-01

    This review discusses how the T-cell compartment in common variable immunodeficiency is marked by the premature arrest in thymic output, leading to T-cell exhaustion and immune dysregulation. Although B cells have been the main focus of the disorder, ample experimental data suggest that T-cell abnormalities can be seen in a large proportion of Freiburg Group 1a patients and those suffering from inflammatory complications. The reductions in T-cell receptor excision circles, naïve T cells, invariant NKT cells and regulatory T cells suggest a diminished thymic output, while CD8 T cells are driven towards exhaustion either via an antigen-dependent or an antigen-independent manner. The theoretical risk of anti-T-cell therapies is discussed, highlighting the need for an international effort in generating longitudinal data in addition to better-defined underlying molecular characterisation. PMID:27153873

  1. Prevalence of inherited prothrombotic abnormalities and central venous catheter-related thrombosis in haematopoietic stem cell transplants recipients.

    PubMed

    Abdelkefi, A; Ben Romdhane, N; Kriaa, A; Chelli, M; Torjman, L; Ladeb, S; Ben Othman, T; Lakhal, A; Guermazi, S; Ben Hassen, A; Ladeb, F; Ben Abdeladhim, A

    2005-11-01

    In this prospective study, we assessed the incidence of central venous catheter (CVC)-related thrombosis in haematopoietic stem cell transplant (HSCT) recipients. We determined the contribution of inherited prothrombotic abnormalities in blood coagulation to CVC-related thrombosis in these patients. The study was conducted between May 2002 and September 2004. CVCs were externalized, nontunneled, polyurethane double lumen catheters. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. All patients were systematically examined by ultrasonography just before, or <24 h after, catheter removal, and in case of clinical signs of thrombosis. A total of 171 patients were included during the 28-month study period. Five (2.9%) and three (1.7%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.6%). In total, 10 patients (5.8%) were heterozygous for the factor V Leiden mutation, and one patient had heterozygous prothrombin G20210A mutation (0.6%). We observed a CVC-related thrombosis in 13 patients (7.6%). Thrombosis was diagnosed in four out of 20 patients (20%) with a inherited prothrombotic abnormality compared to nine of 151 patients (6%) who did not have a thrombophilic marker (relative risk 3.3 CI 95% 1.1-9.9). Our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in HSCT recipients. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in these patients, a priori determination of inherited prothrombotic abnormalities may form a basis to guide these treatment decisions. PMID:16151418

  2. Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

    PubMed

    Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

    2016-01-30

    Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. PMID:26435258

  3. Nonthermal-plasma-mediated animal cell death

    NASA Astrophysics Data System (ADS)

    Kim, Wanil; Woo, Kyung-Chul; Kim, Gyoo-Cheon; Kim, Kyong-Tai

    2011-01-01

    Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.

  4. Self-correction of chromosomal abnormalities in human preimplantation embryos and embryonic stem cells.

    PubMed

    Bazrgar, Masood; Gourabi, Hamid; Valojerdi, Mojtaba Rezazadeh; Yazdi, Poopak Eftekhari; Baharvand, Hossein

    2013-09-01

    Aneuploidy is commonly seen in human preimplantation embryos, most particularly at the cleavage stage because of genome activation by third cell division. Aneuploid embryos have been used for the derivation of normal embryonic stem cell (ESC) lines and developmental modeling. This review addresses aneuploidies in human preimplantation embryos and human ESCs and the potential of self-correction of these aberrations. Diploid-aneuploid mosaicism is the most frequent abnormality observed; hence, embryos selected by preimplantation genetic diagnosis at the cleavage or blastocyst stage could be partly abnormal. Differentiation is known as the barrier for eliminating mosaic embryos by death and/or decreased division of abnormal cells. However, some mosaicisms, such as copy number variations could be compatible with live birth. Several reasons have been proposed for self-correction of aneuploidies during later stages of development, including primary misdiagnosis, allocation of the aneuploidy in the trophectoderm, cell growth advantage of diploid cells in mosaic embryos, lagging of aneuploid cell division, extrusion or duplication of an aneuploid chromosome, and the abundance of DNA repair gene products. Although more studies are needed to understand the mechanisms of self-correction as a rare phenomenon, most likely, it is related to overcoming mosaicism. PMID:23557100

  5. Electrocardiographic abnormalities and dyslipidaemic syndrome in children with sickle cell anaemia

    PubMed Central

    Adegoke, Samuel Ademola; Okeniyi, John Akintunde Oladotun; Akintunde, Adeseye Abiodun

    2016-01-01

    Summary Background Lipid and electrocardiographic (ECG) abnormalities have been reported in adults with sickle cell anaemia (SCA) and may reflect underlying structural and/ or functional damage. However, the relationship between ECG and lipid abnormalities among children with sickle cell disease is not fully understood. Objectives To compare the steady-state lipid and ECG abnormalities in children with SCA to the controls and examine the hypothesis that lipid abnormalities are closely related to electrocardiographic abnormalities, and therefore are a reflection of cardiac damage among these children. Methods: Clinical, laboratory and ECG profiles of 62 children with SCA and 40 age- and gender-matched haemoglobin AA controls were compared. The influence of clinical characteristics, lipids profiles, markers of haemolysis, and renal and hepatic dysfunction on ECG pattern in children with SCA was then determined. Results The patients had lower average diastolic and mean arterial blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than the controls, (p = 0.001, 0.002, 0.000 and 0.000, respectively). The mean triglyceride level was significantly higher (p < 0.001), while high-density lipoprotein cholesterol (HDL-C) levels were comparable (p = 0.858). The cases were about six times more likely to have left ventricular hypertrophy than the controls (OR = 6.4, 95% CI = 2.7–15.6, p = 0.000). Haematocrit level had a negative correlation with QTC (r = –0.3, p = 0.016) and QT intervals (r = – 0.3, p = 0.044). Triglyceride levels had a positive correlation with the PR interval (r = 0.3, p = 0.012), while serum alanine transferase (ALT) concentrations had an inverse correlation with PR interval (r = –0.3, p = 0.015). There was no statistical difference in the sociodemographic and clinical characteristics of the SCA children with or without ECG abnormalities. However, the mean triglyceride and serum ALT levels in those with ECG

  6. Plasma cell adaptation to enhance particle acceleration

    SciTech Connect

    Ragheb, M. S.

    2008-06-15

    A plasma study is performed in order to construct a cell for plasma acceleration purpose. As well, a multicell design is introduced for the injection of beam driver application. The suggested idea is experimentally demonstrated for two plasma cell configuration. The preformed plasma is obtained by a symmetrically driven capacitive audio frequency discharge. It is featured by its moderate pressure of 0.1-0.2 Torr, low consumption power of 130 W maximum, low discharge voltage and frequency up to 950 V and 20 kHz, respectively, and high plasma density from 10{sup 11} to 10{sup 15} cm{sup -3}. The electron temperature obtained by Langmuir double probe varies from 1 up to 16 eV. It is observed that the increases of the discharge voltage and frequency enlarge the plasma parameters to their maximum values. The plasma cell filled with different gases demonstrates that the Ar and He gases manifest the highest ionization efficiency exceeding 100% at 950 V and 20 kHz. The formed plasma is cold; its density is uniform and stable along the positive column for long competitive lifetime. Showing that it follows the conditions to enhance particle acceleration and in conjunction with its periphery devices form a plasma cell that could be extended to serve this purpose. Demonstrating that an injected electron beam into the extended preformed plasma could follow, to long distance, a continuous trajectory of uniform density. Such plasma generated by H{sub 2} or Ar gases is suggested to be used, respectively, for low-density or higher density beam driver.

  7. Coating Solar Cells By Microwave Plasma Deposition

    NASA Technical Reports Server (NTRS)

    Minaee, Behrooz; Chitre, Sanjeev R.; Zahedi, Narges

    1991-01-01

    Antireflection films deposited on silicon solar cells at high production rates with microwave-enhanced plasma deposition. Microwave energy at frequency of 2.45 GHz generates plasma in mixture of gases, from which thin film of silicon nitride deposits on silicon substrates. Reaction temperature relatively low (only 250 degrees C), and film deposition rate more than 500 Angstrom/minute - 2 to 5 times faster. Quality of antireflection film similar to that produced by chemical-vapor deposition. Uses less power and consumes smaller quantities of gas. Species formed in plasma longer lived and dissociate reactants in region of chamber well away from plasma-generation region.

  8. Abnormalities in Mitochondrial Structure in Cells from Patients with Bipolar Disorder

    PubMed Central

    Cataldo, Anne M.; McPhie, Donna L.; Lange, Nicholas T.; Punzell, Steven; Elmiligy, Sarah; Ye, Nancy Z.; Froimowitz, Michael P.; Hassinger, Linda C.; Menesale, Emily B.; Sargent, Laura W.; Logan, David J.; Carpenter, Anne E.; Cohen, Bruce M.

    2010-01-01

    Postmortem, genetic, brain imaging, and peripheral cell studies all support decreased mitochondrial activity as a factor in the manifestation of Bipolar Disorder (BD). Because abnormal mitochondrial morphology is often linked to altered energy metabolism, we investigated whether changes in mitochondrial structure were present in brain and peripheral cells of patients with BD. Mitochondria from patients with BD exhibited size and distributional abnormalities compared with psychiatrically-healthy age-matched controls. Specifically, in brain, individual mitochondria profiles had significantly smaller areas, on average, in BD samples (P = 0.03). In peripheral cells, mitochondria in BD samples were concentrated proportionately more within the perinuclear region than in distal processes (P = 0.0008). These mitochondrial changes did not appear to be correlated with exposure to lithium. Also, these abnormalities in brain and peripheral cells were independent of substantial changes in the actin or tubulin cytoskeleton with which mitochondria interact. The observed changes in mitochondrial size and distribution may be linked to energy deficits and, therefore, may have consequences for cell plasticity, resilience, and survival in patients with BD, especially in brain, which has a high-energy requirement. The findings may have implications for diagnosis, if they are specific to BD, and for treatment, if they provide clues as to the underlying pathophysiology of BD. PMID:20566748

  9. Preoperative preparation of the patient with the abnormalities of red and white blood cells.

    PubMed

    Tomin, Dragica

    2011-01-01

    The complete peripheral blood count analysis including laboratory screening tests of haemostasis and coagulation should be done in every patient before surgery, in order to detect specific abnormalities for primary or secundary haematologic disorder. These abnormalities might be very important course of perioperative and postoperative complications. Anaemia is the most frequent haematologic abnormality seen during preoperative period. Therapy approach depends on the type and anaemia degree, and also on the type and time of surgery. If surgery is not urgent specific therapy according to the anaemia type (iron therapy, vitamin B12, folic acid, corticosteroids, recombinant erythropoietin) should be given in all anaemias with deficiency of iron, megaloblastic anaemias, acquired haemolytic anaemias and anaemias in end stage renal disease. Transfusion of red cells are most frequently given in patients with normovolemic anaemias with haemoglobin level of 10.0 g/dl and hematocrit of 0.30, but lower levels in haemodynamic stable patients. Venesections should be done in patients with erythrocytosis in order to reduce total red cell volume, but taking into account the perioperative bleeding. Patients with leukocyte abnormalities suspected on primary haematologic disorder need urgent haematologic diagnostic procedures. In patients with leucocytosis the actual level of neutropenia is the bigger problem than the level of leucocytosis. In those patients treatment generally involves preventing infections, managing of febrile neutropenia with broad spectrum antibiotics and antifungal drugs, treatment with recombinant granulocyte hematopoetic factor, rarely transfusions of granulocyte concentrates and intravenous immunoglobulins. PMID:21879654

  10. Abnormal spatial diffusion of Ca2+ in F508del-CFTR airway epithelial cells

    PubMed Central

    Antigny, Fabrice; Norez, Caroline; Cantereau, Anne; Becq, Frédéric; Vandebrouck, Clarisse

    2008-01-01

    Background In airway epithelial cells, calcium mobilization can be elicited by selective autocrine and/or paracrine activation of apical or basolateral membrane heterotrimeric G protein-coupled receptors linked to phospholipase C (PLC) stimulation, which generates inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG) and induces Ca2+ release from endoplasmic reticulum (ER) stores. Methods In the present study, we monitored the cytosolic Ca2+ transients using the UV light photolysis technique to uncage caged Ca2+ or caged IP3 into the cytosol of loaded airway epithelial cells of cystic fibrosis (CF) and non-CF origin. We compared in these cells the types of Ca2+ receptors present in the ER, and measured their Ca2+ dependent activity before and after correction of F508del-CFTR abnormal trafficking either by low temperature or by the pharmacological corrector miglustat (N-butyldeoxynojirimycin). Results We showed reduction of the inositol 1,4,5-trisphosphate receptors (IP3R) dependent-Ca2+ response following both correcting treatments compared to uncorrected cells in such a way that Ca2+ responses (CF+treatment vs wild-type cells) were normalized. This normalization of the Ca2+ rate does not affect the activity of Ca2+-dependent chloride channel in miglustat-treated CF cells. Using two inhibitors of IP3R1, we observed a decrease of the implication of IP3R1 in the Ca2+ response in CF corrected cells. We observed a similar Ca2+ mobilization between CF-KM4 cells and CFTR-cDNA transfected CF cells (CF-KM4-reverted). When we restored the F508del-CFTR trafficking in CFTR-reverted cells, the specific IP3R activity was also reduced to a similar level as in non CF cells. At the structural level, the ER morphology of CF cells was highly condensed around the nucleus while in non CF cells or corrected CF cells the ER was extended at the totality of cell. Conclusion These results suggest reversal of the IP3R dysfunction in F508del-CFTR epithelial cells by correction of

  11. Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice

    PubMed Central

    Li, Ming; Guo, Kequan; Adachi, Yasushi; Ikehara, Susumu

    2016-01-01

    Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice. PMID:26840301

  12. Automatic recognition of abnormal cells in cytological tests using multispectral imaging

    NASA Astrophysics Data System (ADS)

    Gertych, A.; Galliano, G.; Bose, S.; Farkas, D. L.

    2010-03-01

    Cervical cancer is the leading cause of gynecologic disease-related death worldwide, but is almost completely preventable with regular screening, for which cytological testing is a method of choice. Although such testing has radically lowered the death rate from cervical cancer, it is plagued by low sensitivity and inter-observer variability. Moreover, its effectiveness is still restricted because the recognition of shape and morphology of nuclei is compromised by overlapping and clumped cells. Multispectral imaging can aid enhanced morphological characterization of cytological specimens. Features including spectral intensity and texture, reflecting relevant morphological differences between normal and abnormal cells, can be derived from cytopathology images and utilized in a detection/classification scheme. Our automated processing of multispectral image cubes yields nuclear objects which are subjected to classification facilitated by a library of spectral signatures obtained from normal and abnormal cells, as marked by experts. Clumps are processed separately with reduced set of signatures. Implementation of this method yields high rate of successful detection and classification of nuclei into predefined malignant and premalignant types and correlates well with those obtained by an expert. Our multispectral approach may have an impact on the diagnostic workflow of cytological tests. Abnormal cells can be automatically highlighted and quantified, thus objectivity and performance of the reading can be improved in a way which is currently unavailable in clinical setting.

  13. Comparison of Efficacy in Abnormal Cervical Cell Detection between Liquid-based Cytology and Conventional Cytology.

    PubMed

    Tanabodee, Jitraporn; Thepsuwan, Kitisak; Karalak, Anant; Laoaree, Orawan; Krachang, Anong; Manmatt, Kittipong; Anontwatanawong, Nualpan

    2015-01-01

    This study was conducted to 1206 women who had cervical cancer screening at Chonburi Cancer Hospital. The spilt-sample study aimed to compare the efficacy of abnormal cervical cells detection between liquid-based cytology (LBC) and conventional cytology (CC). The collection of cervical cells was performed by broom and directly smeared on a glass slide for CC then the rest of specimen was prepared for LBC. All slides were evaluated and classified by The Bethesda System. The results of the two cytological tests were compared to the gold standard. The LBC smear significantly decreased inflammatory cell and thick smear on slides. These two techniques were not difference in detection rate of abnormal cytology and had high cytological diagnostic agreement of 95.7%. The histologic diagnosis of cervical tissue was used as the gold standard in 103 cases. Sensitivity, specificity, positive predictive value, negative predictive value, false positive, false negative and accuracy of LBC at ASC-US cut off were 81.4, 75.0, 70.0, 84.9, 25.0, 18.6 and 77.7%, respectively. CC had higher false positive and false negative than LBC. LBC had shown higher sensitivity, specificity, PPV, NPV and accuracy than CC but no statistical significance. In conclusion, LBC method can improve specimen quality, more sensitive, specific and accurate at ASC-US cut off and as effective as CC in detecting cervical epithelial cell abnormalities. PMID:26514540

  14. Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities.

    PubMed

    Fukuda, Terunobu; Kominami, Kanoko; Wang, Shujie; Togashi, Hideru; Hirata, Ken-ichi; Mizoguchi, Akira; Rikitake, Yoshiyuki; Takai, Yoshimi

    2014-01-01

    The organ of Corti consists of sensory hair cells (HCs) interdigitated with nonsensory supporting cells (SCs) to form a checkerboard-like cellular pattern. HCs are equipped with hair bundles on their apical surfaces. We previously reported that cell-adhesive nectins regulate the checkerboard-like cellular patterning of HCs and SCs in the mouse auditory epithelium. Nectin-1 and -3 are differentially expressed in normal HCs and SCs, respectively, and in Nectin-3-deficient mice a number of HCs are aberrantly attached to each other. We show here that these aberrantly attached HCs in Nectin-3-deficient mice, but not unattached ones, show disturbances of the orientation and morphology of the hair bundles and the positioning of the kinocilium, with additional abnormal localisation of cadherin-catenin complexes and the apical-basal polarity proteins Pals1 and Par-3. These results indicate that, owing to the loss of Nectin-3, hair cells contact each other inappropriately and form abnormal junctions, ultimately resulting in abnormal hair bundle orientation and morphology. PMID:24381198

  15. Spectral Cytopathology of Cervical Samples: Detecting Cellular Abnormalities in Cytologically Normal Cells

    PubMed Central

    Schubert, Jennifer M.; Bird, Benjamin; Papamarkakis, Kostas; Miljković, Miloš; Bedrossian, Kristi; Laver, Nora; Diem, Max

    2010-01-01

    Aim Spectral Cytopathology (SCP) is a novel spectroscopic method for objective and unsupervised classification of individual exfoliated cells. The limitations of conventional cytopathology are well-recognized within the pathology community. In SCP, cellular differentiation is made by observing molecular changes in the nucleus and the cytoplasm, which may or may not produce morphological changes detectable by conventional cytopathology. This proof of concept study demonstrates SCP’s potential as an enhancing tool for cytopathologists by aiding in the accurate and reproducible diagnosis of cells in all states of disease. Method Infrared spectra are collected from cervical cells deposited onto reflectively coated glass slides. Each cell has a corresponding infrared spectrum that describes its unique biochemical composition. Spectral data are processed and analyzed by an unsupervised chemometric algorithm, Principal Component Analysis (PCA). Results In this blind study, cervical samples are classified by analyzing the spectra of morphologically normal looking squamous cells from normal samples and samples diagnosed by conventional cytopathology with low grade squamous intraepithelial lesions (LSIL). SCP discriminated cytopathological diagnoses amongst twelve different cervical samples with a high degree of specificity and sensitivity. SCP also correlated two samples with abnormal spectral changes: these samples had a normal cytopathological diagnosis but had a history of abnormal cervical cytology. The spectral changes observed in the morphologically normal looking cells are most likely due to an infection with human papillomavirus, HPV. HPV DNA testing was conducted on five additional samples, and SCP accurately differentiated these samples by their HPV status. Conclusions SCP tracks biochemical variations in cells that are consistent with the onset of disease. HPV has been implicated as the cause of these changes detected spectroscopically. SCP does not depend on

  16. Deficiency of Cardiolipin Synthase Causes Abnormal Mitochondrial Function and Morphology in Germ Cells of Caenorhabditis elegans*

    PubMed Central

    Sakamoto, Taro; Inoue, Takao; Otomo, Yukae; Yokomori, Nagaharu; Ohno, Motoki; Arai, Hiroyuki; Nakagawa, Yasuhito

    2012-01-01

    Cardiolipin (CL) is a major membrane phospholipid specifically localized in mitochondria. At the cellular level, CL has been shown to have a role in mitochondrial energy production, mitochondrial membrane dynamics, and the triggering of apoptosis. However, the in vivo role of CL in multicellular organisms is largely unknown. In this study, by analyzing deletion mutants of a CL synthase gene (crls-1) in Caenorhabditis elegans, we demonstrated that CL depletion selectively caused abnormal mitochondrial function and morphology in germ cells but not in somatic cell types such as muscle cells. crls-1 mutants reached adulthood but were sterile with reduced germ cell proliferation and impaired oogenesis. In the gonad of crls-1 mutants, mitochondrial membrane potential was significantly decreased, and the structure of the mitochondrial cristae was disrupted. Contrary to the abnormalities in the gonad, somatic tissues in crls-1 mutants appeared normal with respect to cell proliferation, mitochondrial function, and mitochondrial morphology. Increased susceptibility to CL depletion in germ cells was also observed in mutants of phosphatidylglycerophosphate synthase, an enzyme responsible for producing phosphatidylglycerol, a precursor phospholipid of CL. We propose that the contribution of CL to mitochondrial function and morphology is different among the cell types in C. elegans. PMID:22174409

  17. Rapid degradation of abnormal proteins in vacuoles from Acer pseudoplatanus L. cells

    SciTech Connect

    Canut, H.; Alibert, G.; Carrasco, A.; Boudet, A.M.

    1986-06-01

    In Acer pseudoplatanus cells, the proteins synthesized in the presence of an amino acid analog ((/sup 14/C)p-fluorophenylalanine), were degraded more rapidly than normal ones ((/sup 14/C)phenylalanine as precursor). The degradation of an important part of these abnormal proteins occurred inside the vacuoles. The degradation process was not apparently associated to a specific proteolytic system but was related to a preferential transfer of these aberrant proteins from the cytoplasm to the vacuole.

  18. Significance of Persistent Cytogenetic Abnormalities at Myeloablative Allogeneic Stem Cell Transplantation in First Complete Remission

    PubMed Central

    Oran, Betul; Popat, Uday; Rondon, Gabriella; Ravandi, Farhad; Garcia-Manero, Guillermo; Abruzzo, Lynn; Andersson, Borje S.; Bashir, Qaiser; Chen, Julianne; Kebriaei, Partow; Khouri, Issa F.; Koca, Ebru; Qazilbash, Muzaffar H.; Champlin, Richard; de Lima, Marcos

    2014-01-01

    Risk stratification is important to identify acute myeloid leukemia (AML) patients that might benefit from allogeneic hematopoietic stem cell transplantation (allo-HCT) in first complete remission (CR1). We retrospectively studied 150 AML patients with diagnostic cytogenetic abnormalities receiving myeloablative allo-HCT in CR1 to determine the prognostic impact of persistent cytogenetic abnormalities at allo-HCT. Three risk groups were identified: First group of patients with favorable/intermediate cytogenetics at diagnosis (n=49) and the second group with unfavorable cytogenetics at diagnosis but without the presence of persistent abnormal clone at allo-HCT (n=83) had similar 3-year leukemia free survival (LFS) of 58%-60% despite increased 3-year relapse incidence (RI) of 32.3% observed in the second risk group versus 16.8% in the first group. Third group of patients with unfavorable cytogenetics at diagnosis and persistence of that clone at allo-HCT (n=15) represented the worst prognostic group with 3-year RI of 57.5% and 3-year LFS of 29.2%. These data suggest that AML patients with unfavorable cytogenetics at diagnosis and persistence of abnormal clone at allo-HCT have high risk of relapse after allo-HCT. These patients should be considered for clinical trials designed to optimize conditioning regimens and/or to use preemptive strategies in the post-transplant setting to decrease the relapse incidence. PMID:22982533

  19. Kidney disease associated with plasma cell dyscrasias

    PubMed Central

    Goes, Nelson B.; Spitzer, Thomas R.; Raje, Noopur S.; Humphreys, Benjamin D.; Anderson, Kenneth C.; Richardson, Paul G.

    2010-01-01

    Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve. PMID:20462963

  20. Transmission of clonal chromosomal abnormalities in human hematopoietic stem and progenitor cells surviving radiation exposure.

    PubMed

    Kraft, Daniela; Ritter, Sylvia; Durante, Marco; Seifried, Erhard; Fournier, Claudia; Tonn, Torsten

    2015-07-01

    In radiation-induced acute myeloid leukemia (rAML), clonal chromosomal abnormalities are often observed in bone marrow cells of patients, suggesting that their formation is crucial in the development of the disease. Since rAML is considered to originate from hematopoietic stem and progenitor cells (HSPC), we investigated the frequency and spectrum of radiation-induced chromosomal abnormalities in human CD34(+) cells. We then measured stable chromosomal abnormalities, a possible biomarker of leukemia risk, in clonally expanded cell populations which were grown for 14 days in a 3D-matrix (CFU-assay). We compared two radiation qualities used in radiotherapy, sparsely ionizing X-rays and densely ionizing carbon ions (29 and 60-85 keV/μm, doses between 0.5 and 4 Gy). Only a negligible number of de novo arising, unstable aberrations (≤ 0.05 aberrations/cell, 97% breaks) were measured in the descendants of irradiated HSPC. However, stable aberrations were detected in colonies formed by irradiated HSPC. All cells of the affected colonies exhibited one or more identical aberrations, indicating their clonal origin. The majority of the clonal rearrangements (92%) were simple exchanges such as translocations (77%) and pericentric inversions (15%), which are known to contribute to the development of rAML. Carbon ions were more efficient in inducing cell killing (maximum of ∼ 30-35% apoptotic cells for 2 Gy carbon ions compared to ∼ 25% for X-rays) and chromosomal aberrations in the first cell-cycle after exposure (∼ 70% and ∼ 40% for 1 Gy of carbon ions and X-rays, respectively), with a higher fraction of non-transmissible aberrations. In contrast, for both radiation qualities the percentage of clones with chromosomal abnormalities was similar (40%). Using the frequency of colonies with clonal aberrations as a surrogate marker for the leukemia risk following radiotherapy of solid tumors, charged particle therapy is not expected to lead to an increased risk of

  1. Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure.

    PubMed

    Triggianese, P; Perricone, C; Conigliaro, P; Chimenti, M S; Perricone, R; De Carolis, C

    2016-03-01

    Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only

  2. Abnormal cell surface antigen expression in individuals with variant CD45 splicing and histiocytosis.

    PubMed

    Boxall, Sally; McCormick, James; Beverley, Peter; Strobel, Stephan; De Filippi, Paola; Dawes, Ritu; Klersy, Catherine; Clementi, Rita; De Juli, Emanuella; Ferster, Aline; Wallace, Diana; Aricò, Maurizio; Danesino, Cezare; Tchilian, Elma

    2004-03-01

    Hemophagocytic lymphohistiocytosis (HLH) and Langerhans cell histiocytosis (LCH) are members of a group of rare heterogenous disorders, the histiocytoses, characterized by uncontrolled accumulation of pleomorphic infiltrates of leukocytes. The etiology of these diseases is mainly unknown. CD45 is a hemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signaling in lymphocytes and different patterns of CD45 splicing are associated with distinct functions. Recently a polymorphism (C77G) in exon 4 of CD45 causing abnormal CD45 splicing and a point mutation affecting CD45 dimerization were implicated in multiple sclerosis in humans and lymphoproliferation and autoimmunity in mice respectively. Here we show that two patients with HLH exhibited abnormal CD45 splicing caused by the C77G variant allele, while a further 21 HLH patients have normal CD45. We have also examined 62 LCH patients and found three to have the C77G mutation. Peripheral blood thymus-derived (T) CD8(+) cells from normal individuals carrying the C77G mutation show a significant decrease in the proportion of cells expressing L-selectin and increased frequency of cells with LFA-1(hi) expression. It remains to be established whether C77G is a contributing factor in these histiocytic disorders. PMID:14630980

  3. Canine Systemic Lupus Erythematosus. TRANSMISSION OF SEROLOGIC ABNORMALITIES BY CELL-FREE FILTRATES

    PubMed Central

    Lewis, Robert M.; Andre-Schwartz, Janine; Harbis, Gerald S.; Hirsch, Martin S.; Black, Paul H.; Schwartz, Robert S.

    1973-01-01

    The presence of viruses was sought in a colony of dogs bred from parents with systemic lupus crythematosus (SLE). Cell-free filtrates prepared from the spleens of these animals were injected into newborn dogs, mice, and rats. The canine recipients developed antinuclear antibody (ANA) and positive lupus erythematosus (LE) cell tests: ANA and, in some cases, antinative DNA antibodies were produced by the murine recipients: no abnormalities were detected in the rats. Serial passage of spleen cells or cell-free filtrates of spleen tissue in syngeneic mice reduced the time required for appearance of ANA from 9 to 4 mo. Some murine recipients of the canine filtrate developed malignant lymphomas. Murine leukemia viruses were identified in these tumors by electron microscopic, virologic, and serologic technics. These neoplasms, but not other tumors known to contain murine leukemia viruses, were associated with the production of ANA. Puppies inoculated with the canine filtrate-induced mouse lymphoma developed ANA and positive LE cell tests within 4 mo. The results were interpreted to indicate the presence in canine SLE of a virus capable of: (a) inducing the serologic abnormalities of SLE in normal dogs and mice: (b) activating latent murine leukemia viruses: and (c) spreading by both horizonal and vertical routes. Images PMID:4124208

  4. Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells.

    PubMed

    Zou, Jianlong; Hu, Bo; Arpag, Sezgi; Yan, Qing; Hamilton, Audra; Zeng, Yuan-Shan; Vanoye, Carlos G; Li, Jun

    2015-04-29

    Loss of function of FIG4 leads to Charcot-Marie-Tooth disease Type 4J, Yunis-Varon syndrome, or an epilepsy syndrome. FIG4 is a phosphatase with its catalytic specificity toward 5'-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2). However, the loss of FIG4 decreases PI3,5P2 levels likely due to FIG4's dominant effect in scaffolding a PI3,5P2 synthetic protein complex. At the cellular level, all these diseases share similar pathology with abnormal lysosomal storage and neuronal degeneration. Mice with no FIG4 expression (Fig4(-/-)) recapitulate the pathology in humans with FIG4 deficiency. Using a flow cytometry technique that rapidly quantifies lysosome sizes, we detected an impaired lysosomal fission, but normal fusion, in Fig4(-/-) cells. The fission defect was associated with a robust increase of intralysosomal Ca(2+) in Fig4(-/-) cells, including FIG4-deficient neurons. This finding was consistent with a suppressed Ca(2+) efflux of lysosomes because the endogenous ligand of lysosomal Ca(2+) channel TRPML1 is PI3,5P2 that is deficient in Fig4(-/-) cells. We reactivated the TRPML1 channels by application of TRPML1 synthetic ligand, ML-SA1. This treatment reduced the intralysosomal Ca(2+) level and rescued abnormal lysosomal storage in Fig4(-/-) culture cells and ex vivo DRGs. Furthermore, we found that the suppressed Ca(2+) efflux in Fig4(-/-) culture cells and Fig4(-/-) mouse brains profoundly downregulated the expression/activity of dynamin-1, a GTPase known to scissor organelle membranes during fission. This downregulation made dynamin-1 unavailable for lysosomal fission. Together, our study revealed a novel mechanism explaining abnormal lysosomal storage in FIG4 deficiency. Synthetic ligands of the TRPML1 may become a potential therapy against diseases with FIG4 deficiency. PMID:25926456

  5. [Molecular pathology of plasma cell neoplasms].

    PubMed

    Fend, F

    2010-10-01

    Plasma cell myeloma (PCM) and related immunosecretory disorders are a group of B-cell proliferations with a wide clinical and prognostic spectrum, characterized by the production of monoclonal immunoglobulin by immortalized plasma cells. Recent years have seen an explosion in knowledge on the genetic basis and biology of these diseases, followed by improved clinical risk stratification and the introduction of novel therapeutic concepts, such as treatment with proteasome inhibitors or immunomodulatory substances. PCM is a common malignancy, accounting for approximately 10% of all hematological neoplasms. There is good evidence to support a multistep transformation process in plasma cell neoplasms, which corresponds to clinically discernible disease stages. Monoclonal gammopathy of unknown significance is a common asymptomatic precursor lesion for PCM which carries an approximately 1% annual risk for progression. Terminal disease stages are characterized by increasing genetic complexity and independence from bone marrow stromal cells and show a rapidly increasing tumour load with severe clinical symptoms. Modern diagnostics of plasma cell neoplasms require inclusion of clinical, morphological, immunophenotypical and cytogenetic features to allow for individual risk assessment and therapy planning. PMID:20852863

  6. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    PubMed

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  7. Solar cell modules for plasma interaction evaluation

    NASA Technical Reports Server (NTRS)

    1981-01-01

    A plasma interaction analysis in support of the solar electric propulsion subsystem examined the effects of a large high voltage solar array interacting with an ion thruster produced plasma. Two solar array test modules consisting of 36 large area wraparound contact solar cells welded to a flexible Kapton integrated circuit substrate were abricated. The modules contained certain features of the effects of insulation, din-holes, and bonding of the cell to the substrate and a ground plane. The possibility of a significant power loss occurring due to the collection of charged particles on the solar array interconnects was the focus of the research.

  8. Abnormal mitosis in hypertetraploid cells causes aberrant nuclear morphology in association with H2O2-induced premature senescence.

    PubMed

    Ohshima, Susumu

    2008-09-01

    Aberrant nuclear morphology, such as nuclei with irregular shapes or fragmented nuclei, is often observed in senescent cells, but its biological significance is not fully understood. My previous study showed that aberrant nuclear morphology in senescent human fibroblasts is attributable to abnormal mitosis in later passages. In this study, the production of abnormal nuclei in association with premature senescence was investigated. Premature senescence was induced by brief exposure of human fibroblasts to hydrogen peroxide (H(2)O(2)), and mitosis was observed by time-lapse microscopy. In addition, cell cycle and nuclear morphology after exposure to H(2)O(2) were also analyzed using a laser scanning cytometer. Time-lapse analysis revealed that the induction of premature senescence caused abnormal mitoses, such as mitotic slippage or incomplete mitosis, especially in later days after H(2)O(2) exposure and often resulted in abnormal nuclear morphology. Analysis by laser scanning cytometer showed significantly higher frequency of abnormal cells with deformed nuclei and abnormal mitotic cells with misaligned chromosomes in a hypertetraploid subpopulation. These results suggest that unstable hypertetraploid cells, formed in association with H(2)O(2)-induced premature senescence, cause abnormal mitosis that leads to aberrant nuclear morphology. PMID:18618767

  9. DNA damage in oral cancer cells induced by nitrogen atmospheric pressure plasma jets

    NASA Astrophysics Data System (ADS)

    Han, Xu; Klas, Matej; Liu, Yueying; Stack, M. Sharon; Ptasinska, Sylwia

    2013-09-01

    The nitrogen atmospheric pressure plasma jet (APPJ) has been shown to effectively induce DNA double strand breaks in SCC-25 oral cancer cells. The APPJ source constructed in our laboratory consists of two external electrodes wrapping around a quartz tube and nitrogen as a feed gas and operates based on dielectric barrier gas discharge. Generally, it is more challenging to ignite plasma in N2 atmosphere than in noble gases. However, this design provides additional advantages such as lower costs compared to the noble gases for future clinical operation. Different parameters of the APPJ configuration were tested in order to determine radiation dosage. To explore the effects of delayed damage and cell self-repairing, various incubation times of cells after plasma treatment were also performed. Reactive species generated in plasma jet and in liquid environment are essential to be identified and quantified, with the aim of unfolding the mystery of detailed mechanisms for plasma-induced cell apoptosis. Moreover, from the comparison of plasma treatment effect on normal oral cells OKF6T, an insight to the selectivity for cancer treatment by APPJ can be explored. All of these studies are critical to better understand the damage responses of normal and abnormal cellular systems to plasma radiation, which are useful for the development of advanced plasma therapy for cancer treatment at a later stage.

  10. A novel scheme for abnormal cell detection in Pap smear images

    NASA Astrophysics Data System (ADS)

    Zhao, Tong; Wachman, Elliot S.; Farkas, Daniel L.

    2004-07-01

    Finding malignant cells in Pap smear images is a "needle in a haystack"-type problem, tedious, labor-intensive and error-prone. It is therefore desirable to have an automatic screening tool in order that human experts can concentrate on the evaluation of the more difficult cases. Most research on automatic cervical screening tries to extract morphometric and texture features at the cell level, in accordance with the NIH "The Bethesda System" rules. Due to variances in image quality and features, such as brightness, magnification and focus, morphometric and texture analysis is insufficient to provide robust cervical cancer detection. Using a microscopic spectral imaging system, we have produced a set of multispectral Pap smear images with wavelengths from 400 nm to 690 nm, containing both spectral signatures and spatial attributes. We describe a novel scheme that combines spatial information (including texture and morphometric features) with spectral information to significantly improve abnormal cell detection. Three kinds of wavelet features, orthogonal, bi-orthogonal and non-orthogonal, are carefully chosen to optimize recognition performance. Multispectral feature sets are then extracted in the wavelet domain. Using a Back-Propagation Neural Network classifier that greatly decreases the influence of spurious events, we obtain a classification error rate of 5%. Cell morphometric features, such as area and shape, are then used to eliminate most remaining small artifacts. We report initial results from 149 cells from 40 separate image sets, in which only one abnormal cell was missed (TPR = 97.6%) and one normal cell was falsely classified as cancerous (FPR = 1%).

  11. Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms

    PubMed Central

    Asai, Takashi; Hatlen, Megan A.; Lossos, Chen; Ndiaye-Lobry, Delphine; Deblasio, Anthony; Murata, Kazunori; Fleisher, Martin; Cortizas, Elena M.; Verdun, Ramiro E.; Petrini, John; Nimer, Stephen D.

    2016-01-01

    Multiple myeloma is a plasma cell neoplasm with an extremely variable clinical course. Animal models are needed to better understand its pathophysiology and for preclinical testing of potential therapeutic agents. Hematopoietic cells expressing the hypermorphic Rad50s allele show hematopoietic failure, which can be mitigated by the lack of a transcription factor, Mef/Elf4. However, we find that 70% of Mef−/−Rad50s/s mice die from multiple myeloma or other plasma cell neoplasms. These mice initially show an abnormal plasma cell proliferation and monoclonal protein production, and then develop anemia and a decreased bone mineral density. Tumor cells can be serially transplanted and according to array CGH and whole exome sequencing, the pathogenesis of plasma cell neoplasms in these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor. This model recapitulates the systemic manifestations of human plasma cell neoplasms, and implicates cooperativity between the Rad50s and Mef/Elf4 pathways in initiating myelomagenic mutations that promote plasma cell transformation. PMID:26961797

  12. Male rat infertility induction/spermatozoa and epididymal plasma abnormalities after oral administration of Kalanchoe gastonis bonnieri natural juice.

    PubMed

    de la Luz Miranda-Beltrán, María; Puebla-Pérez, Ana María; Guzmán-Sánchez, Arnoldo; Huacuja Ruiz, Luis

    2003-04-01

    Natural aqueous crude extracts (NACE) of several Crassulaceae family plants have been applied as a vaginal contraceptive by the populace. The aim of this work was to evaluate the inhibition of fertility in male Wistar rats and some physiological and biochemical changes in spermatozoa and epididymal plasma induced by NACE from Kalanchoe gastonis bonnieri (K. g. b.) (Crassulaceae). The NACE was obtained by mechanic pressure on grinding fresh plant leaves. Sublethal doses (150-300 mg/kg body weight) of NACE were orally administered to adult and fertile male rats daily for 30 days in a search for a contraceptive effect, and physiological and biochemical modifications on sperm cells and cauda epididymal plasma. The toxicity studies revealed that the lethal dose (LD(50)) calculated was 11 g/kg body weight. Sublethal doses induced 50%-100% fertility inhibition, with 100% recovery of fertility 30 days after stopping the treatment. The sperm motility, viability and spermatic density were also significantly decreased (p < 0.001). The outstanding biochemical change observed in the cauda epididymal plasma was a decrease of carnitine concentration. The NACE of K. gastonis contains one substance active on fertility by affecting spermatozoa motility, viability and sperm density with a significantly decreased carnitine and sialic acid (p < 0.001) in the caudal epididymal plasma. PMID:12722131

  13. Antigen presenting cell abnormalities in the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis.

    PubMed

    Hersrud, Samantha L; Kovács, Attila D; Pearce, David A

    2016-07-01

    Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3(-/-) mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3(-/-) cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3(-/-) cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL. PMID:27101989

  14. Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons?

    PubMed

    McCullumsmith, R E; O'Donovan, S M; Drummond, J B; Benesh, F S; Simmons, M; Roberts, R; Lauriat, T; Haroutunian, V; Meador-Woodruff, J H

    2016-06-01

    Excitatory amino-acid transporters (EAATs) bind and transport glutamate, limiting spillover from synapses due to their dense perisynaptic expression primarily on astroglia. Converging evidence suggests that abnormalities in the astroglial glutamate transporter localization and function may underlie a disease mechanism with pathological glutamate spillover as well as alterations in the kinetics of perisynaptic glutamate buffering and uptake contributing to dysfunction of thalamo-cortical circuits in schizophrenia. We explored this hypothesis by performing cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of the thalamus in an elderly cohort of subjects with schizophrenia. We found decreased protein expression for the typically astroglial-localized glutamate transporters in the mediodorsal and ventral tier nuclei. We next used laser-capture microdissection and quantitative polymerase chain reaction to assess cell-level expression of the transporters and their splice variants. In the mediodorsal nucleus, we found lower expression of transporter transcripts in a population of cells enriched for astrocytes, and higher expression of transporter transcripts in a population of cells enriched for relay neurons. We confirmed expression of transporter protein in neurons in schizophrenia using dual-label immunofluorescence. Finally, the pattern of transporter mRNA and protein expression in rodents treated for 9 months with antipsychotic medication suggests that our findings are not due to the effects of antipsychotic treatment. We found a compensatory increase in transporter expression in neurons that might be secondary to a loss of transporter expression in astrocytes. These changes suggest a profound abnormality in astrocyte functions that support, nourish and maintain neuronal fidelity and synaptic activity. PMID:26416546

  15. Abnormal cleavage of APP impairs its functions in cell adhesion and migration.

    PubMed

    Sheng, Baiyang; Song, Bo; Zheng, Zhenhuan; Zhou, Fangfang; Lu, Guangyuan; Zhao, Nanming; Zhang, Xiufang; Gong, Yandao

    2009-02-01

    Amyloid precursor protein (APP) is expressed ubiquitously but its wrong cleavage only occurs in central nervous system. In this research, overexpression of wild type human APP695 was found to stimulate the adhesion and migration of N2a cells. In the cells co-transfected by familial Alzheimer's disease (FAD)-linked Swedish mutant of APP695 gene plus big up tri, openE9 deleted presenilin1 gene (N2a/Swe. big up tri, open9), however, this stimulating function was impaired compared to that in the cells co-transfected by Swedish mutant of APP695 gene plus dominant negative mutant of presenilin1 D385A gene (N2a/Swe.385). Furthermore, it was also found that the phosphorylation of FAK Tyr-861 and GSK-3beta Ser-9 was reduced in N2a/Swe.Delta9 cells, which can be possibly taken as a reasonable explanation for the underlying mechanism. Our results suggest that impaired cell adhesion and migration induced by abnormal cleavage of APP could contribute to the pathological effects in FAD brain. PMID:19056463

  16. Urine - abnormal color

    MedlinePlus

    ... straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. Causes Abnormal urine color may ... red blood cells, or mucus in the urine. Dark brown but clear urine is a sign of ...

  17. Transgenic sickle cell trait mice do not exhibit abnormal thermoregulatory and stress responses to heat shock exposure.

    PubMed

    Chen, Yifan; Islam, Aminul

    2016-07-01

    There remains controversy over whether individuals with sickle cell trait (SCT) are vulnerable to health risks during physical activity in high temperatures. We examined thermoregulatory and stress-related responses to heat exposure in SCT and wild-type (WT) mice. No significant differences in core temperature (Tc) were observed between SCT and WT mice during heat exposure. There was no correlation between peak Tc during heat exposure and levels of hemoglobin S in SCT mice. Basal levels of circulating inflammatory and stress-related markers were not significantly different between SCT and WT mice. Although heat exposure caused significant increases in plasma interleukins 1β and 6, and 8-isoprostane in SCT and WT mice, no differences were found between SCT and WT mice with similar thermal response profiles during heat exposure. SCT mice had significantly higher expression of heat shock protein 72 in heart, liver and gastrocnemius muscle than WT mice under control and post-heat conditions. In conclusion, there is neither thermoregulatory dysfunction nor abnormal stress-related response in SCT mice exposed to moderate heat. The hemoglobin variant in mice is associated with altered tissue stress protein homeostasis. PMID:27282581

  18. Galactosylceramidase deficiency causes sperm abnormalities in the mouse model of globoid cell leukodystrophy

    SciTech Connect

    Luddi, A.; Strazza, M.; Carbone, M.; Moretti, E.; Costantino-Ceccarini, E. . E-mail: costantino@unisi.it

    2005-03-10

    The classical recessive mouse mutant, 'the twitcher,' is one of the several animal models of the human globoid cell leukodystrophy (Krabbe disease) caused by a deficiency in the gene encoding the lysosomal enzyme galactosylceramidase (GALC). The failure to hydrolyze galactosylceramide (gal-cer) and galactosylsphingosine (psychosine) leads to degeneration of oligodendrocytes and severe demyelination. Substrate for GALC is also the galactosyl-alkyl-acyl-glycerol (GalAAG), precursor of the seminolipid, the most abundant glycolipid in spermatozoa of mammals. In this paper, we report the pathobiology of the testis and sperm in the twitcher mouse and demonstrate the importance of GALC for normal sperm maturation and function. The GALC deficit results in accumulation of GalAAG in the testis of the twitcher mouse. Morphological studies revealed that affected spermatozoa have abnormally swollen acrosomes and angulation of the flagellum mainly at midpiece-principal piece junction. Multiple folding of the principal piece was also observed. Electron microscopy analysis showed that in the twitcher sperm, acrosomal membrane is redundant, detached from the nucleus and folded over. Disorganization and abnormal arrangements of the axoneme components were also detected. These results provide in vivo evidence that GALC plays a critical role in spermiogenesis.

  19. Craniofacial bone abnormalities and malocclusion in individuals with sickle cell anemia: a critical review of the literature

    PubMed Central

    Costa, Cyrene Piazera Silva; de Carvalho, Halinna Larissa Cruz Correia; Thomaz, Erika Bárbara Abreu Fonseca; Sousa, Soraia de Fátima Carvalho

    2012-01-01

    This study aims to critically review the literature in respect to craniofacial bone abnormalities and malocclusion in sickle cell anemia individuals. The Bireme and Pubmed electronic databases were searched using the following keywords: malocclusion, maxillofacial abnormalities, and Angle Class I, Class II and lass III malocclusions combined with sickle cell anemia. The search was limited to publications in English, Spanish or Portuguese with review articles and clinical cases being excluded from this study. Ten scientific publications were identified, of which three were not included as they were review articles. There was a consistent observation of orthodontic and orthopedic variations associated with sickle cell anemia, especially maxillary protrusions. However, convenience sampling, sometimes without any control group, and the lack of estimates of association and hypotheses testing undermined the possibility of causal inferences. It was concluded that despite the high frequency of craniofacial bone abnormalities and malocclusion among patients with sickle cell anemia, there is insufficient scientific proof that this disease causes malocclusion PMID:23049386

  20. Plural light chains in a single plasma cell of a monoclonal gammopathy undetermined significance case: an ultrastructural study.

    PubMed

    Saito, Nagahito; Konishi, Kohei; Ohta, Shuichi; Kondo, Takeshi; Kato, Mototsugu; Hashino, Satoshi; Takeda, Hiroshi; Asaka, Masahiro; Ooi, Hong-Kean

    2007-02-01

    A 44-year-old man was found to have M-proteins of IgG consisting of kappa- and lambda-chains in serum without lymphadenopathy or splenomegaly. The serum concentrations of IgG, IgA and IgM were within normal limits. Bone marrow examination showed normal cellular marrow containing 6.3% of plasma cells with no abnormal features. No chromosomal abnormality was observed at all. The patient was diagnosed as having monoclonal gammopathy of undetermined significance. The bone marrow plasma cells possessed free kappa- and lambda-chains in Golgi apparatus, rough endoplasmic reticula and cytoplasmic matrices. Plural light chains were simultaneously produced with the same heavy chain in a plasma cell by immunoelectron microscopy. This is the first report in the world of a monoclonal gammopathy of undetermined significance producing plural light chains with the same heavy chain. PMID:17506772

  1. Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells

    PubMed Central

    Ishibashi, Daisuke; Homma, Takujiro; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Takatsuki, Hanae; Atarashi, Ryuichiro; Nishida, Noriyuki

    2015-01-01

    Prion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in the central nervous system. With the aim of elucidating the mechanism underlying the accumulation and degradation of PrPSc, we investigated the role of autophagy in its degradation, using cultured cells stably infected with distinct prion strains. The effects of pharmacological compounds that inhibit or stimulate the cellular signal transduction pathways that mediate autophagy during PrPSc degradation were evaluated. The accumulation of PrPSc in cells persistently infected with the prion strain Fukuoka-1 (FK), derived from a patient with Gerstmann–Sträussler–Scheinker syndrome, was significantly increased in cultures treated with the macroautophagy inhibitor 3-methyladenine (3MA) but substantially reduced in those treated with the macroautophagy inducer rapamycin. The decrease in FK-derived PrPSc levels was mediated, at least in part, by the phosphatidylinositol 3-kinase/MEK signalling pathway. By contrast, neither rapamycin nor 3MA had any apparently effect on PrPSc from either the 22L or the Chandler strain, indicating that the degradation of PrPSc in host cells might be strain-dependent. PMID:26368533

  2. Plasma membrane phosphoinositide balance regulates cell shape during Drosophila embryo morphogenesis

    PubMed Central

    Reversi, Alessandra; Loeser, Eva; Subramanian, Devaraj; Schultz, Carsten

    2014-01-01

    Remodeling of cell shape during morphogenesis is driven by the coordinated expansion and contraction of specific plasma membrane domains. Loss of this coordination results in abnormal cell shape and embryonic lethality. Here, we show that plasma membrane lipid composition plays a key role in coordinating plasma membrane contraction during expansion. We found that an increase in PI(4,5)P2 levels caused premature actomyosin contraction, resulting in the formation of shortened cells. Conversely, acute depletion of PI(4,5)P2 blocked plasma membrane expansion and led to premature actomyosin disassembly. PI(4,5)P2-mediated contractility is counteracted by PI(3,4,5)P3 and the zygotic gene bottleneck, which acts by limiting myosin recruitment during plasma membrane expansion. Collectively, these data support a model in which the ratio of PI(4,5)P2/PI(3,4,5)P3 coordinates actomyosin contractility and plasma membrane expansion during tissue morphogenesis, thus ensuring proper cell shape. PMID:24798734

  3. Micronuclei and nuclear abnormalities in buccal mucosa cells in patients with anorexia and bulimia nervosa.

    PubMed

    Torres-Bugarín, Olivia; Pacheco-Gutiérrez, Angélica Guadalupe; Vázquez-Valls, Eduardo; Ramos-Ibarra, María Luisa; Torres-Mendoza, Blanca Miriam

    2014-11-01

    The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future. PMID:25232046

  4. Comprehensive molecular cytogenetic investigation of chromosomal abnormalities in human medulloblastoma cell lines and xenograft.

    PubMed Central

    Aldosari, Naji; Wiltshire, Rodney N.; Dutra, Amalia; Schrock, Evelin; McLendon, Roger E.; Friedman, Henry S.; Bigner, Darell D.; Bigner, Sandra H.

    2002-01-01

    Cell lines and xenografts derived from medulloblastomas are useful tools to investigate the chromosomal changes in these tumors. Here we used G-banding, fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization to study 4 medulloblastoma cell lines and 1 xenograft. Cell line D-425 Med had a relatively simple karyotype, with a terminal deletion of 10q and amplification of MYC in double-minutes (dmins). FISH demonstrated that an apparent isochromosome (17q) by routine karyotyping was actually an unbalanced translocation between 2 copies of chromosome 17. Cell line D-556 Med also had a simple near-diploid stemline with an unbalanced 1;13 translocation resulting in a gain of 1q, an isochromosome (17q), and dmins. These findings were initially described using routine G-banded preparations, and FISH showed that the dmins were an amplification of MYC and the i(17q) was an isodicentric 17q chromosome. The other finding was confirmed by FISH, SKY, and comparative genomic hybridization. Cell lines D-721 Med and D-581 Med had complex karyotypic patterns that could be completely characterized only when FISH and SKY were used. Xenograft D-690 Med also had a complex pattern that FISH and SKY were helpful in completely elucidating. Interestingly, balanced reciprocal translocations were seen as well as complicated unbalanced translocations and marker chromosomes. Comparative genomic hybridization demonstrated only a deletion of 10q22-10q24, supporting the idea that despite the complexity of the chromosomal rearrangements, minimal alterations in the overall chromosomal content had occurred. This study demonstrates that routine cytogenetic preparations are adequate to describe chromosomal abnormalities in occasional medulloblastoma samples, but a broader spectrum of molecular cytogenetic methods is required to completely analyze most of these tumor samples. PMID:11916498

  5. Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage.

    PubMed

    Schoenhals, Matthieu; Jourdan, Michel; Seckinger, Anja; Pantesco, Véronique; Hose, Dirk; Kassambara, Alboukadel; Moreaux, Jérôme; Klein, Bernard

    2016-07-17

    A role of the transcription factor Krüppel-like factor 4 (KLF4) in the generation of mature plasma cells (PC) is unknown. Indeed, KLF4 is critical in controlling the differentiation of various cell linages, particularly monocytes and epithelial cells. KLF4 is expressed at low levels in pro-B cells and its expression increases as they mature into pre-B cells, resting naïve B cells and memory B cells. We show here that KLF4 is expressed in human bone marrow plasma cells and its function was studied using an in vitro model of differentiation of memory B cells into long lived plasma cells. KLF4 is rapidly lost when memory B cells differentiate into highly cell cycling plasmablasts, poorly cycling early plasma cells and then quiescent long-lived plasma cells. A forced expression of KLF4 in plasmablasts enhances the yield of their differentiation into early plasma cell and long lived plasma cells, by inhibiting apoptosis and upregulating previously unknown plasma cell pathways. PMID:27230497

  6. Dynamics of photoinduced cell plasma membrane injury.

    PubMed Central

    Thorpe, W P; Toner, M; Ezzell, R M; Tompkins, R G; Yarmush, M L

    1995-01-01

    We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes. Images FIGURE 2 FIGURE 3 FIGURE 6 FIGURE 7 PMID:7612864

  7. Sulforaphane induces DNA damage and mitotic abnormalities in human osteosarcoma MG-63 cells: correlation with cell cycle arrest and apoptosis.

    PubMed

    Ferreira de Oliveira, José Miguel P; Remédios, Catarina; Oliveira, Helena; Pinto, Pedro; Pinho, Francisco; Pinho, Sónia; Costa, Maria; Santos, Conceição

    2014-01-01

    Osteosarcoma is a recalcitrant bone malignancy with poor responsiveness to treatments; therefore, new chemotherapeutic compounds are needed. Sulforaphane (SFN) has been considered a promising chemotherapeutic compound for several types of tumors by inducing apoptosis and cytostasis, but its effects (e.g., genotoxicity) in osteosarcoma cells remains exploratory. In this work, the MG-63 osteosarcoma cell line was exposed to SFN up to 20 μM for 24 and 48 h. SFN induced G2/M phase arrest and decreased nuclear division index, associated with disruption of cytoskeletal organization. Noteworthy, SFN induced a transcriptome response supportive of G2/M phase arrest, namely a decrease in Chk1- and Cdc25C-encoding transcripts, and an increase in Cdk1-encoding transcripts. After 48-h exposure, SFN at a dietary concentration (5 μM) contributed to genomic instability in the MG-63 cells as confirmed by increased number of DNA breaks, clastogenicity, and nuclear and mitotic abnormalities. The increased formation of nucleoplasmic bridges, micronuclei, and apoptotic cells positively correlated with loss of viability. These results suggest that genotoxic damage is an important step for SFN-induced cytotoxicity in MG-63 cells. In conclusion, SFN shows potential to induce genotoxic damage at low concentrations and such potential deserves further investigation in other tumor cell types. PMID:24405297

  8. Red blood cell abnormalities and the pathogenesis of anemia in end-stage renal disease.

    PubMed

    Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G

    2016-08-01

    Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia. PMID:26948278

  9. Cell Adhesion to Plasma-Coated PVC

    PubMed Central

    Rangel, Elidiane C.; de Souza, Eduardo S.; de Moraes, Francine S.; Duek, Eliana A. R.; Lucchesi, Carolina; Schreiner, Wido H.; Durrant, Steven F.; Cruz, Nilson C.

    2014-01-01

    To produce environments suitable for cell culture, thin polymer films were deposited onto commercial PVC plates from radiofrequency acetylene-argon plasmas. The proportion of argon in the plasmas, PAr, was varied from 5.3 to 65.8%. The adhesion and growth of Vero cells on the coated surfaces were examined for different incubation times. Cytotoxicity tests were performed using spectroscopic methods. Carbon, O, and N were detected in all the samples using XPS. Roughness remained almost unchanged in the samples prepared with 5.3 and 28.9% but tended to increase for the films deposited with PAr between 28.9 and 55.3%. Surface free energy increased with increasing PAr, except for the sample prepared at 28.9% of Ar, which presented the least reactive surface. Cells proliferated on all the samples, including the bare PVC. Independently of the deposition condition there was no evidence of cytotoxicity, indicating the viability of such coatings for designing biocompatible devices. PMID:25247202

  10. Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice

    PubMed Central

    Wang, Ruey-Sheng; Chang, Heng-Yu; Kao, Shu-Huei; Kao, Cheng-Heng; Wu, Yi-Chen; Yeh, Shuyuan; Tzeng, Chii-Reuy; Chang, Chawnshang

    2015-01-01

    In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR−/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II. Interestingly, we found these AR−/− female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells. PMID:25941928

  11. JAK2V617F-positive endothelial cells contribute to clotting abnormalities in myeloproliferative neoplasms

    PubMed Central

    Etheridge, S. Leah; Roh, Michelle E.; Cosgrove, Megan E.; Sangkhae, Veena; Fox, Norma E.; Chen, Junmei; López, José A.; Kaushansky, Kenneth; Hitchcock, Ian S.

    2014-01-01

    The Janus kinase 2 (JAK2) V617F mutation is the primary pathogenic mutation in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Although thrombohemorrhagic incidents are the most common causes of morbidity and mortality in patients with MPNs, the events causing these clotting abnormalities remain unclear. To identify the cells responsible for the dysfunctional hemostasis, we used transgenic mice expressing JAK2V617F in specific lineages involved in thrombosis and hemostasis. When JAK2V617F was expressed in both hematopoietic and endothelial cells (ECs), the mice developed a significant MPN, characterized by thrombocytosis, neutrophilia, and splenomegaly. However, despite having significantly higher platelet counts than controls, these mice showed severely attenuated thrombosis following injury. Interestingly, platelet activation and aggregation in response to agonists was unaltered by JAK2V617F expression. Subsequent bone marrow transplants revealed the contribution of both endothelial and hematopoietic compartments to the attenuated thrombosis. Furthermore, we identified a potential mechanism for this phenotype through JAK2V617F-regulated inhibition of von Willebrand factor (VWF) function and/or secretion. JAK2V617F+ mice display a condition similar to acquired von Willebrand syndrome, exhibiting significantly less high molecular weight VWF and reduced agglutination to ristocetin. These findings greatly advance our understanding of thrombohemorrhagic events in MPNs and highlight the critical role of ECs in the pathology of hematopoietic malignancies. PMID:24469804

  12. Micronuclei Frequencies and Nuclear Abnormalities in Oral Exfoliated Cells of Nuclear Power Plant Workers

    PubMed Central

    Babannavar, Roopa; Lohra, Abhishek; Kodgi, Ashwin; Bapure, Sunil; Rao, Yogesh; J., Arun; Malghan, Manjunath

    2014-01-01

    Aim: Biomonitoring provides a useful tool to estimate the genetic risk from exposure to genotoxic agents. The aim of this study was to evaluate the frequencies of Micronuclei (MN) and other Nuclear abnormalities (NA) from exfoliated oral mucosal cells in Nuclear Power Station (NPS) workers. Materials and Methods: Micronucleus frequencies in oral exfoliated cells were done from individuals not known to be exposed to either environmental or occupational carcinogens (Group I). Similarly samples were obtained from full-time Nuclear Power Station (NPS) workers with absence of Leukemia and any malignancy (Group II) and workers diagnosed as leukemic patients and undergoing treatment (Group III). Results: There was statistically significant difference between Group I, Group II & Group III. MN and NA frequencies in Leukemic Patients were significantly higher than those in exposed workers &control groups (p < 0.05). Conclusion: MN and other NA reflect genetic changes, events associated with malignancies. Therefore, there is a need to educate those who work in NPS about the potential hazard of occupational exposure and the importance of using protective measures. PMID:25654022

  13. Interaction of Low Temperature Plasmas with Prokaryotic and Eukaryotic Cells

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir

    2008-10-01

    Due to promising possibilities for their use in medical applications such as wound healing, surface modification of biocompatible materials, and the sterilization of reusable heat-sensitive medical instruments, low temperature plasmas and plasma jets are making big strides as a technology that can potentially be used in medicine^1-2. At this stage of research, fundamental questions about the effects of plasma on prokaryotic and eukaryotic cells are still not completely answered. An in-depth understanding of the pathway whereby cold plasma interact with biological cells is necessary before real applications can emerge. In this paper, first an overview of non-equilibrium plasma sources (both low and high pressures) will be presented. Secondly, the effects of plasma on bacterial cells will be discussed. Here, the roles of the various plasma agents in the inactivation process will be outlined. In particular, the effects of UV and that of various reactive species (O3, O, OH) are highlighted. Thirdly, preliminary findings on the effects of plasma on few types of eukaryotic cells will be presented. How plasma affects eukaryotic cells, such as mammalian cells, is very important in applications where the viability/preservation of the cells could be an issue (such as in wound treatment). Another interesting aspect is the triggering of apoptosis (programmed cell death). Some investigators have claimed that plasma is able to induce apoptosis in some types of cancer cells. If successfully replicated, this can open up a novel method of cancer treatment. In this talk however, I will briefly focus more on the wound healing potential of cold plasmas. ^1E. A. Blakely, K. A. Bjornstad, J. E. Galvin, O. R. Monteiro, and I. G. Brown, ``Selective Neuron Growth on Ion Implanted and Plasma Deposited Surfaces'', In Proc. IEEE Int. Conf. Plasma Sci., (2002), p. 253. ^2M. Laroussi, ``Non-thermal Decontamination of Biological Media by Atmospheric Pressure Plasmas: Review, Analysis, and

  14. Hematopoietic Cell and Renal Transplantation in Plasma Cell Dyscrasia Patients.

    PubMed

    Baraldi, Olga; Grandinetti, Valeria; Donati, Gabriele; Comai, Giorgia; Battaglino, Giuseppe; Cuna, Vania; Capelli, Irene; Sala, Elisa; La Manna, Gaetano

    2016-01-01

    Gammopathies, multiple myeloma, and amyloidosis are plasma dyscrasias characterized by clonal proliferation and immunoglobulin overproduction. Renal impairment is the most common and serious complication with an incidence of 20-30% patients at the diagnosis. Kidney transplant has not been considered feasible in the presence of plasma dyscrasias because the immunosuppressive therapy may increase the risk of neoplasia progression, and paraproteins may affect the graft. However, recent advances in clinical management of multiple myeloma and other gammopathies allow considering kidney transplant as a possible alternative to dialysis. Numerous evidence indicates the direct relationship between hematological remission and renal function restoring. The combination of kidney and hematopoietic cell transplant has been reported as a promising approach to reestablish end-organ function and effectively treat the underlying disease. This review describes current protocols used to perform kidney transplantation in patients with plasma dyscrasias. PMID:26160700

  15. Biphenotypic plasma cell myeloma: two cases of plasma cell neoplasm with a coexpression of kappa and lambda light chains

    PubMed Central

    Jiwani, Shahanawaz; Bornhost, Joshua; Alapat, Daisy

    2015-01-01

    Plasma cell neoplasm (PCM) is a medullary and extra medullary proliferation of clonal plasma cells that occurs due to accidental translocation of proto-oncogenes into immunoglobulin (Ig) gene loci. While the majority of plasma cell neoplasms are monoclonal, up to 2% of the PCMs [1] considered being biclonal based on electrophoretic analysis, characterized by secretion of paraprotein with two distinct heavy chains or light chains are possible and present unique diagnostic challenges. Methods: Traditionally protein electrophoresis has been used to diagnose, characterize, and monitor progression of plasma cell neoplasm. To characterize neoplastic plasma cells, in our institution, other ancillary studies, including in situ hybridization, flow cytometric analyses of plasma cell surface markers and cytoplasmic immunoglobulins with DNA ploidy, are also utilized routinely. Results: We present two cases of plasma cell myeloma in which the neoplastic plasma cells shows production of cytoplasmic kappa and lambda light chain, with secretion of free lambda light chain only. Co-expression of kappa and lambda light chain by the same neoplastic plasma cells is a rare but reported phenomenon. Conclusions: Our study indicates that serum electrophoresis alone could mischaracterize biphenotypic myeloma as monotypic plasma cell myelomas in the absence of additional testing methods. PMID:26339430

  16. Plasmocytoma, multiple myeloma and plasma cell neoplasms in orofacial region.

    PubMed

    Zajko, J; Czako, L; Galis, B

    2016-01-01

    A neoplastic proliferation of B cell lymphocyte is called plasma cell neoplasms, results from malignant plasma cells transformation in bone marrow. The authors present a clinical study and overview of this pathology in maxillofacial region for six years (Tab. 2, Ref. 14). PMID:27546545

  17. Performance of the CellaVision® DM96 system for detecting red blood cell morphologic abnormalities

    PubMed Central

    Horn, Christopher L.; Mansoor, Adnan; Wood, Brenda; Nelson, Heather; Higa, Diane; Lee, Lik Hang; Naugler, Christopher

    2015-01-01

    Background: Red blood cell (RBC) analysis is a key feature in the evaluation of hematological disorders. The gold standard light microscopy technique has high sensitivity, but is a relativity time-consuming and labor intensive procedure. This study tested the sensitivity and specificity of gold standard light microscopy manual differential to the CellaVision® DM96 (CCS; CellaVision, Lund, Sweden) automated image analysis system, which takes digital images of samples at high magnification and compares these images with an artificial neural network based on a database of cells and preclassified according to RBC morphology. Methods: In this study, 212 abnormal peripheral blood smears within the Calgary Laboratory Services network of hospital laboratories were selected and assessed for 15 different RBC morphologic abnormalities by manual microscopy. The same samples were reassessed as a manual addition from the instrument screen using the CellaVision® DM96 system with 8 microscope high power fields (×100 objective and a 22 mm ocular). The results of the investigation were then used to calculate the sensitivity and specificity of the CellaVision® DM96 system in reference to light microscopy. Results: The sensitivity ranged from a low of 33% (RBC agglutination) to a high of 100% (sickle cells, stomatocytes). The remainder of the RBC abnormalities tested somewhere between these two extremes. The specificity ranged from 84% (schistocytes) to 99.5% (sickle cells, stomatocytes). Conclusions: Our results showed generally high specificities but variable sensitivities for RBC morphologic abnormalities. PMID:25774322

  18. Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells.

    PubMed

    McCole, Ruth B; Fonseka, Chamith Y; Koren, Amnon; Wu, C-Ting

    2014-10-01

    Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell. Here we address the process by which CNVs become depleted of UCEs. We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions. PMID:25340765

  19. Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells

    PubMed Central

    Torres-Bugarín, Olivia; Zavala-Cerna, María Guadalupe; Nava, Arnulfo; Flores-García, Aurelio; Ramos-Ibarra, María Luisa

    2014-01-01

    The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique. PMID:24778463

  20. Abnormal Interactions between Perifollicular Mast Cells and CD8+ T-Cells May Contribute to the Pathogenesis of Alopecia Areata

    PubMed Central

    Bertolini, Marta; Zilio, Federica; Rossi, Alfredo; Gilhar, Amos; Keren, Aviad; Meyer, Katja C.; Wang, Eddy; Funk, Wolfgang; McElwee, Kevin; Paus, Ralf

    2014-01-01

    Alopecia areata (AA) is a CD8+ T-cell dependent autoimmune disease of the hair follicle (HF) in which the collapse of HF immune privilege (IP) plays a key role. Mast cells (MCs) are crucial immunomodulatory cells implicated in the regulation of T cell-dependent immunity, IP, and hair growth. Therefore, we explored the role of MCs in AA pathogenesis, focusing on MC interactions with CD8+ T-cells in vivo, in both human and mouse skin with AA lesions. Quantitative (immuno-)histomorphometry revealed that the number, degranulation and proliferation of perifollicular MCs are significantly increased in human AA lesions compared to healthy or non-lesional control skin, most prominently in subacute AA. In AA patients, perifollicular MCs showed decreased TGFβ1 and IL-10 but increased tryptase immunoreactivity, suggesting that MCs switch from an immuno-inhibitory to a pro-inflammatory phenotype. This concept was supported by a decreased number of IL-10+ and PD-L1+ MCs, while OX40L+, CD30L+, 4–1BBL+ or ICAM-1+ MCs were increased in AA. Lesional AA-HFs also displayed significantly more peri- and intrafollicular- CD8+ T-cells as well as more physical MC/CD8+ T-cell contacts than healthy or non-lesional human control skin. During the interaction with CD8+ T-cells, AA MCs prominently expressed MHC class I and OX40L, and sometimes 4–1BBL or ICAM-1, suggesting that MC may present autoantigens to CD8+ T-cells and/or co-stimulatory signals. Abnormal MC numbers, activities, and interactions with CD8+ T-cells were also seen in the grafted C3H/HeJ mouse model of AA and in a new humanized mouse model for AA. These phenomenological in vivo data suggest the novel AA pathobiology concept that perifollicular MCs are skewed towards pro-inflammatory activities that facilitate cross-talk with CD8+ T-cells in this disease, thus contributing to triggering HF-IP collapse in AA. If confirmed, MCs and their CD8+ T-cell interactions could become a promising new therapeutic target in the future

  1. Molecular Characterization of Circulating Plasma Cells in Patients with Active Systemic Lupus Erythematosus

    PubMed Central

    Lugar, Patricia L.; Love, Cassandra; Grammer, Amrie C.; Dave, Sandeep S.; Lipsky, Peter E.

    2012-01-01

    Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared. SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P1, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype. PMID:23028528

  2. Development of plasma-on-chip: Plasma treatment for individual cells cultured in media

    NASA Astrophysics Data System (ADS)

    Kumagai, Shinya; Chang, Chun-Yao; Jeong, Jonghyeon; Kobayashi, Mime; Shimizu, Tetsuji; Sasaki, Minoru

    2016-01-01

    A device consisting of Si microwells and microplasma sources has been fabricated for plasma treatment of individual cells cultured in media. We named the device plasma-on-chip. The microwells have through-holes at the bottom where gas–liquid interfaces form when they are filled with media containing biological samples. The microplasma sources, which supply reactive species, are located on the back of each microwell. Through the gas–liquid interface, the reactive species are supplied to the cells. Chlorella cells were used to demonstrate the feasibility of the device and after three minutes of plasma treatment, the fluorescence intensity of Chlorella cells appeared to be decreased. Optical emission spectroscopy identified O and OH radicals in the plasma, which can affect the cells. In the analysis of biological samples such as human cells or tissues, this device raises the possibility of revealing the mechanisms of plasma medicine in more detail.

  3. Frequency of abnormal findings detected by comprehensive clinical evaluation at 1 year after allogeneic hematopoietic cell transplantation.

    PubMed

    Lee, Stephanie J; Seaborn, Travis; Mao, Frances J; Massey, Susan C; Luu, Ngoc Q; Schubert, Mary A; Chien, Jason W; Carpenter, Paul A; Moravec, Carina; Martin, Paul J; Flowers, Mary E D

    2009-04-01

    Consensus guidelines recommend various screening examinations for survivors after allogeneic hematopoietic cell transplantation (HCT), but how often these examinations detect abnormal findings is unknown. We reviewed the medical records of 118 patients who received comprehensive, standardized evaluations at 1 year after allogeneic HCT at Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance. Abnormal findings were common, including moderate to severe pulmonary dysfunction (16%), fasting hyperlipidemia (56%), osteopenia (52%), osteoporosis (6%), and active chronic graft-versus-host disease (cGVHD) (64%). Recurrent malignancy (4%) and cGVHD (29%) were detected in previously unsuspected cases. Only 3% of patients had no abnormal findings. We conclude that comprehensive evaluation at 1 year after allogeneic HCT detects a high prevalence of medical problems. Longer follow-up is needed to determine whether early detection and intervention affect later morbidity and mortality. PMID:19285628

  4. Effect of Lycium bararum polysaccharides on methylmercury-induced abnormal differentiation of hippocampal stem cells

    PubMed Central

    Tian, Jian-Ying; Chen, Wei-Wei; Cui, Jing; Wang, Hao; Chao, Ci; Lu, Zhi-Yan; Bi, Yong-Yi

    2016-01-01

    The aim of the present study was to observe the effects of a general extract of Lycium bararum polysaccharides (LBPs) on methylmercury (MeHg)-induced damage in hippocampus neural stem cells (hNSCs). The hippocampal tissues of embryonic day 16 Sprague-Dawley rats were extracted for the isolation, purification and cloning of hNSCs. Following passage and proliferation for 10 days, the cells were allocated at random into the following groups: Control, LBPs, MeHg and MeHg + LBPs. MTT and microtubule-associated protein 2 (MAP-2)/glial fibrillary acidic protein/Hoechst immunofluorescence tests were performed to detect the differentiation and growth of hNSCs in the various groups. The differentiation rate of MeHg-treated hNSCs and the perimeter of MAP-2-positive neurons were 3.632±0.63% and 62.36±5.58 µm, respectively, significantly lower compared with the control group values of 6.500±0.81% and 166±8.16 µm (P<0.05). Furthermore, the differentiation rate and the perimeter of MAP-2-positive neurons in LBPs groups cells was 7.75±0.59% and 253.3±11.21 µm, respectively, significantly higher compared with the control group (P<0.05). The same parameters in the MeHg + LBPs group were 5.92±0.98% and 111.9±6.07 µm, respectively, significantly higher than the MeHg group (P<0.05). The astrocyte differentiation rates in the MeHg and MeHg + LBPs group were 41.19±2.14 and 34.58±1.70, respectively (P<0.05). These results suggest that LBPs may promote the generation and development of new neurons and inhibit the MeHg-induced abnormal differentiation of astrocytes. Thus, LBPs may be considered to be a potential new treatment for MeHg-induced neurotoxicity in hNSCs. PMID:27446261

  5. Responses of cells in plasma-activated medium

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiromasa; Mizuno, Masaaki; Ishikawa, Kenji; Takeda, Keigo; Hashizume, Hiroshi; Nakamura, Kae; Kajiyama, Hiroaki; Kano, Hiroyuki; Okazaki, Yasumasa; Toyokuni, Shinya; Maruyama, Shoichi; Kodera, Yasuhiro; Terasaki, Hiroko; Adachi, Tetsuo; Kato, Masashi; Kikkawa, Fumitaka; Hori, Masaru

    2015-09-01

    Plasma consists of electrons, ions, radicals, and lights, and produces various reactive species in gas and liquid phase. Cells receive various inputs from their circumstances, and induce several physiological outputs. Our goal is to clarify the relationships between plasma inputs and physiological outputs. Plasma-activated medium (PAM) is a circumstance that plasma provides cells and our previous studies suggest that PAM is a promising tool for cancer therapy. However, the mode of actions remains to be elucidated. We propose survival and proliferation signaling networks as well as redox signaling networks are key factors to understand cellular responses of PAM-treated glioblastoma cells.

  6. T cells induce terminal differentiation of transformed B cells to mature plasma cell tumors.

    PubMed

    Hilbert, D M; Shen, M Y; Rapp, U R; Rudikoff, S

    1995-01-31

    Major interest in the analysis of mature plasma cell neoplasias of mice and humans has focused on identification of precursor cells that give rise to mature malignant plasma cells. Although several laboratories have recently suggested that such cells are present in the granulomas of pristane-treated mice and the bone marrow of some multiple myeloma patients, the in vivo cellular interactions required for their differentiation into mature plasma cell tumors remains unclear. Given the extensive interactions of peripheral T cells and normal B cells, we assessed the potential role of T cells in plasma-cell tumor development, by using a myc, raf-containing retrovirus, J3V1, to induce plasmacytomas in normal BALB/c mice, T-cell-deficient nude mice, and T-cell-reconstituted nude mice. The B-lineage tumors arising in normal BALB/c mice were uniformly mature plasmacytomas, most of which secreted immunoglobulin. In contrast, nude mice yielded predominantly non-immunoglobulin-secreting B-cell lymphomas with a phenotype characteristic of peripheral B cells. T-cell reconstitution of nude mice prior to tumor induction resulted in a shift from B-cell lymphomas to plasmacytomas. These results imply that transformation can occur prior to terminal differentiation of B cells and that such transformed cells can be driven to terminal differentiation by peripheral T cells. These findings further suggest that, in human multiple myeloma, the ability of T cells to influence the differentiation state of transformed B cells may provide a mechanism by which malignant plasma cells found in the bone marrow could arise from clonotypically related less-mature B cells found in both the bone marrow and periphery. PMID:7846031

  7. Induction of Aneuploidy, Centrosome Abnormality, Multipolar Spindle, and Multipolar Division in Cultured Mammalian Cells Exposed to an Arsenic Metabolite, Dimethylarsinate.

    PubMed

    Ochi, Takafumi

    2016-01-01

    Toxicological studies of arsenic compounds were conducted in cultured mammalian cells to investigate the effects of glutathione (GSH) depletion. Dimethylarsinate DMA(V) was not cytotoxic in cells depleted of GSH, but was found to be cytotoxic when GSH was present outside the cells. The results suggested that a reactive form of DMA(V) was generated through interaction with GSH. Dimethylarsine iodide DMI(III) was used as a model compound of DMA(III), and the biological effects were investigated. DMI(III) was about 10000 times more toxic to the cells than DMA(V). Chromosome structural aberrations and numerical changes, such as aneuploidy, were induced by DMI(III). DMA(V) induced multiple foci of the centrosome protein, γ-tubulin, which were colocalized with multipolar spindles in mitotic cells. The multiple foci coalesced into a single dot on disruption of the microtubules (MT). However, reorganization of the MT caused multiple foci of γ-tubulin, suggesting that the induction of centrosome abnormalities by DMA(V) required intact MT. Inhibition of the MT-dependent motor, kinesin, prevented formation of multiple foci of γ-tubulin, which pointed to the involvement of the MT-dependent mitotic motor, kinesin, in the maintenance of centrosome abnormalities. DMI(III) caused abnormal cytokinesis (multipolar division). In addition, DMI(III) caused morphological transformation in Syrian hamster embryo cells. Consideration of the overall process following the centrosome abnormalities caused by DMA(V) suggested a mode of cytotoxicity in which the mitotic centrosome is a critical target. PMID:27252065

  8. DASAF: An R Package for Deep Sequencing-Based Detection of Fetal Autosomal Abnormalities from Maternal Cell-Free DNA

    PubMed Central

    Tang, Xiaoyan; Qiu, Feng; Tao, Chunmei; Gao, Junhui; Ma, Mengmeng; Zhong, Tingyan; Cai, JianPing; Li, Yixue

    2016-01-01

    Background. With the development of massively parallel sequencing (MPS), noninvasive prenatal diagnosis using maternal cell-free DNA is fast becoming the preferred method of fetal chromosomal abnormality detection, due to its inherent high accuracy and low risk. Typically, MPS data is parsed to calculate a risk score, which is used to predict whether a fetal chromosome is normal or not. Although there are several highly sensitive and specific MPS data-parsing algorithms, there are currently no tools that implement these methods. Results. We developed an R package, detection of autosomal abnormalities for fetus (DASAF), that implements the three most popular trisomy detection methods—the standard Z-score (STDZ) method, the GC correction Z-score (GCCZ) method, and the internal reference Z-score (IRZ) method—together with one subchromosome abnormality identification method (SCAZ). Conclusions. With the cost of DNA sequencing declining and with advances in personalized medicine, the demand for noninvasive prenatal testing will undoubtedly increase, which will in turn trigger an increase in the tools available for subsequent analysis. DASAF is a user-friendly tool, implemented in R, that supports identification of whole-chromosome as well as subchromosome abnormalities, based on maternal cell-free DNA sequencing data after genome mapping. PMID:27437397

  9. DASAF: An R Package for Deep Sequencing-Based Detection of Fetal Autosomal Abnormalities from Maternal Cell-Free DNA.

    PubMed

    Liu, Baohong; Tang, Xiaoyan; Qiu, Feng; Tao, Chunmei; Gao, Junhui; Ma, Mengmeng; Zhong, Tingyan; Cai, JianPing; Li, Yixue; Ding, Guohui

    2016-01-01

    Background. With the development of massively parallel sequencing (MPS), noninvasive prenatal diagnosis using maternal cell-free DNA is fast becoming the preferred method of fetal chromosomal abnormality detection, due to its inherent high accuracy and low risk. Typically, MPS data is parsed to calculate a risk score, which is used to predict whether a fetal chromosome is normal or not. Although there are several highly sensitive and specific MPS data-parsing algorithms, there are currently no tools that implement these methods. Results. We developed an R package, detection of autosomal abnormalities for fetus (DASAF), that implements the three most popular trisomy detection methods-the standard Z-score (STDZ) method, the GC correction Z-score (GCCZ) method, and the internal reference Z-score (IRZ) method-together with one subchromosome abnormality identification method (SCAZ). Conclusions. With the cost of DNA sequencing declining and with advances in personalized medicine, the demand for noninvasive prenatal testing will undoubtedly increase, which will in turn trigger an increase in the tools available for subsequent analysis. DASAF is a user-friendly tool, implemented in R, that supports identification of whole-chromosome as well as subchromosome abnormalities, based on maternal cell-free DNA sequencing data after genome mapping. PMID:27437397

  10. Immunophenotyping in multiple myeloma and related plasma cell disorders

    PubMed Central

    Kumar, Shaji; Kimlinger, Teresa; Morice, William

    2010-01-01

    SUMMARY Plasma cell disorders form a spectrum ranging from the asymptomatic presence of small monoclonal populations of plasma cells to conditions like plasma cell leukemia and multiple myeloma, in which the bone marrow can be replaced by the accumulation of neoplastic plasma cells. Immunophenotyping has become an invaluable tool in the management of hematological malignancies and is increasingly finding a role in the diagnosis and monitoring of plasma cell disorders. Multiparameter flow cytometry has evolved considerably during the past decade with an increasing ability to screen large numbers of events and to detect multiple antigens at the same time. This, along with a better understanding of the phenotypic heterogeneity of the clonal plasma cells in different disorders, has made immunophenotyping an indispensible tool in the diagnosis, prognostic classification and management of plasma cell disorders. This book chapter addresses the approaches taken to evaluate monoclonal plasma cell disorders, and the different markers and techniques that are important for the study of these diseases. PMID:21112041

  11. Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells

    SciTech Connect

    Adkins, B.; Gandour, D.; Strober, S.; Weissman, I.

    1988-05-15

    Mice given multiple doses of sublethal irradiation to both the thymus and the peripheral lymphoid tissues showed major transient, and some persistent disruptions in general thymic architecture and in thymic stromal components. At 2 wk after total lymphoid irradiation (TLI), the thymus lacked identifiable medullary regions by immunohistochemical analyses. Medullary stromal cells expression MHC Ag or a medullary epithelial cell Ag, as well as medullary macrophages, were undetectable. Instead, the processes of cortical epithelial cells were observed throughout the entire thymus. Strikingly, thymocyte subsets with mature phenotypes (CD4+CD8- and CD4-CD8+) were present in the apparent absence of a medulla. This early, gross effect was rapidly reversed such that by 1 to 2 mo after TLI, medullary areas with MHC Ag-positive cells were evident. However, abnormalities in a subset of medullary stromal cells appeared to be more persistent. Medullary epithelial cells, identified by the MD1 mAb, were greatly reduced in number and abnormally organized for at least 4 mo after TLI. In addition, macrophages containing endogenous peroxidase activity, normally abundant in medullary regions, were undetectable at all times examined after TLI. Therefore, this irradiation regimen induced both transient and long term effects in the thymus, primarily in medullary regions. These results suggest that TLI may be used as an experimental tool for studying the impact of selective depletion of medullary stromal cells on the development of specific T cell functions.

  12. Magnetron cathodes in plasma electrode Pockels cells

    DOEpatents

    Rhodes, M.A.

    1995-04-25

    Magnetron cathodes, which produce high current discharges, form greatly improved plasma electrodes on each side of an electro-optic crystal. The plasma electrode has a low pressure gas region on both sides of the crystal. When the gas is ionized, e.g., by a glow discharge in the low pressure gas, the plasma formed is a good conductor. The gas electrode acts as a highly uniform conducting electrode. Since the plasma is transparent to a high energy laser beam passing through the crystal, the plasma is transparent. A crystal exposed from two sides to such a plasma can be charged up uniformly to any desired voltage. A typical configuration utilizes helium at 50 millitorr operating pressure and 2 kA discharge current. The magnetron cathode produces a more uniform plasma and allows a reduced operating pressure which leads to lower plasma resistivity and a more uniform charge on the crystal. 5 figs.

  13. Magnetron cathodes in plasma electrode pockels cells

    DOEpatents

    Rhodes, Mark A.

    1995-01-01

    Magnetron cathodes, which produce high current discharges, form greatly improved plasma electrodes on each side of an electro-optic crystal. The plasma electrode has a low pressure gas region on both sides of the crystal. When the gas is ionized, e.g., by a glow discharge in the low pressure gas, the plasma formed is a good conductor. The gas electrode acts as a highly uniform conducting electrode. Since the plasma is transparent to a high energy laser beam passing through the crystal, the plasma is transparent. A crystal exposed from two sides to such a plasma can be charged up uniformly to any desired voltage. A typical configuration utilizes helium at 50 millitorr operating. pressure and 2 kA discharge current. The magnetron cathode produces a more uniform plasma and allows a reduced operating pressure which leads to lower plasma resistivity and a more uniform charge on the crystal.

  14. Plasma polymerization for cell adhesive/anti-adhesive implant coating

    NASA Astrophysics Data System (ADS)

    Meichsner, Juergen; Testrich, Holger; Rebl, Henrike; Nebe, Barbara

    2015-09-01

    Plasma polymerization of ethylenediamine (C2H8N2, EDA) and perfluoropropane (C3F8, PFP) with admixture of argon and hydrogen, respectively, was studied using an asymmetric 13.56 MHz CCP. The analysis of the plasma chemical gas phase processes for stable molecules revealed consecutive reactions: C2H8N2 consumption, intermediate product NH3, and main final product HCN. In C3F8- H2 plasma the precursor molecule C3F8 and molecular hydrogen are consumed and HF as well as CF4 and C2F6 are found as main gaseous reaction products. The deposited plasma polymer films on the powered electrode are strongly cross-linked due to ion bombardment. The stable plasma polymerized films from EDA are characterized by high content of nitrogen with N/C ratio of about 0.35. The plasma polymerized fluorocarbon film exhibit a reduced F/C ratio of about 1.2. Adhesion tests with human osteoblast cell line MG-63 on coated Ti6Al4V samples (polished) compared with uncoated reference sample yielded both, the enhanced cell adhesion for plasma polymerized EDA and significantly reduced cell adhesion for fluorocarbon coating, respectively. Aging of the plasma polymerized EDA film, in particular due to the reactions with oxygen from air, showed no significant change in the cell adhesion. The fluorocarbon coating with low cell adhesion is of interest for temporary implants. Funded by the Campus PlasmaMed.

  15. High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett’s Esophagus

    PubMed Central

    Sanchez, Carissa A.; Liu, Karen; Fong, Pui Yee; Li, Xiaohong; Cowan, David S.; Rabinovitch, Peter S.; Reid, Brian J.; Blount, Patricia L.

    2015-01-01

    Purpose Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients. Experimental Design Baseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length. Results High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively). Conclusions The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities. PMID:26230607

  16. iTRAQ-based proteomic analysis of plasma reveals abnormalities in lipid metabolism proteins in chronic kidney disease-related atherosclerosis.

    PubMed

    Luczak, Magdalena; Formanowicz, Dorota; Marczak, Łukasz; Suszyńska-Zajczyk, Joanna; Pawliczak, Elżbieta; Wanic-Kossowska, Maria; Stobiecki, Maciej

    2016-01-01

    Patients with chronic kidney disease (CKD) have a considerably higher risk of death due to cardiovascular causes. Using an iTRAQ MS/MS approach, we investigated the alterations in plasma protein accumulation in patients with CKD and classical cardiovascular disease (CVD) without CKD. The proteomic analysis led to the identification of 130 differentially expressed proteins among CVD and CKD patients and healthy volunteers. Bioinformatics analysis revealed that 29 differentially expressed proteins were involved in lipid metabolism and atherosclerosis, 20 of which were apolipoproteins and constituents of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Although dyslipidemia is common in CKD patients, we found that significant changes in apolipoproteins were not strictly associated with changes in plasma lipid levels. A lack of correlation between apoB and LDL concentration and an inverse relationship of some proteins with the HDL level were revealed. An increased level of apolipoprotein AIV, adiponectin, or apolipoprotein C, despite their anti-atherogenic properties, was not associated with a decrease in cardiovascular event risk in CKD patients. The presence of the distinctive pattern of apolipoproteins demonstrated in this study may suggest that lipid abnormalities in CKD are characterized by more qualitative abnormalities and may be related to HDL function rather than HDL deficiency. PMID:27600335

  17. iTRAQ-based proteomic analysis of plasma reveals abnormalities in lipid metabolism proteins in chronic kidney disease-related atherosclerosis

    PubMed Central

    Luczak, Magdalena; Formanowicz, Dorota; Marczak, Łukasz; Suszyńska-Zajczyk, Joanna; Pawliczak, Elżbieta; Wanic-Kossowska, Maria; Stobiecki, Maciej

    2016-01-01

    Patients with chronic kidney disease (CKD) have a considerably higher risk of death due to cardiovascular causes. Using an iTRAQ MS/MS approach, we investigated the alterations in plasma protein accumulation in patients with CKD and classical cardiovascular disease (CVD) without CKD. The proteomic analysis led to the identification of 130 differentially expressed proteins among CVD and CKD patients and healthy volunteers. Bioinformatics analysis revealed that 29 differentially expressed proteins were involved in lipid metabolism and atherosclerosis, 20 of which were apolipoproteins and constituents of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Although dyslipidemia is common in CKD patients, we found that significant changes in apolipoproteins were not strictly associated with changes in plasma lipid levels. A lack of correlation between apoB and LDL concentration and an inverse relationship of some proteins with the HDL level were revealed. An increased level of apolipoprotein AIV, adiponectin, or apolipoprotein C, despite their anti-atherogenic properties, was not associated with a decrease in cardiovascular event risk in CKD patients. The presence of the distinctive pattern of apolipoproteins demonstrated in this study may suggest that lipid abnormalities in CKD are characterized by more qualitative abnormalities and may be related to HDL function rather than HDL deficiency. PMID:27600335

  18. Robust isolation of malignant plasma cells in multiple myeloma.

    PubMed

    Frigyesi, Ildikó; Adolfsson, Jörgen; Ali, Mina; Christophersen, Mikael Kronborg; Johnsson, Ellinor; Turesson, Ingemar; Gullberg, Urban; Hansson, Markus; Nilsson, Björn

    2014-02-27

    Molecular characterization of malignant plasma cells is increasingly important for diagnostic and therapeutic stratification in multiple myeloma. However, the malignant plasma cells represent a relatively small subset of bone marrow cells, and need to be enriched prior to analysis. Currently, the cell surface marker CD138 (SDC1) is used for this enrichment, but has an important limitation in that its expression decreases rapidly after sampling. Seeking alternatives to CD138, we performed a computational screen for myeloma plasma cell markers and systematically evaluated 7 candidates. Our results conclusively show that the markers CD319 (SLAMF7/CS1) and CD269 (TNFRSF17/BCMA) are considerably more robust than CD138 and enable isolation of myeloma plasma cells under more diverse conditions, including the samples that have been delayed or frozen. Our results form the basis of improved procedures for characterizing cases of multiple myeloma in clinical practice. PMID:24385542

  19. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  20. Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responses.

    PubMed

    Jang, Eunkyeong; Cho, Wang Sik; Oh, Yeon-Kyung; Cho, Mi-La; Kim, Jung Mogg; Paik, Doo-Jin; Youn, Jeehee

    2016-02-01

    Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their phenotypes and ability to prime and induce the differentiation of naive CD4(+) T cells into effector cells in vitro and in vivo. We found that K/BxNsf PCs had lower levels of the Ag presentation machinery and costimulators than K/BxN PCs, and also a lower CD4(+) T cell priming capacity. Autoantigen-pulsed K/BxNsf PCs selectively polarized cognate CD4(+) T cells toward the expression of molecules necessary for Tfh development and function. As a result, the K/BxNsf PC-primed CD4(+) T cells were more effective in stimulating B cells to produce autoantigen-specific IgGs than K/BxN PCs or even dendritic cells. Adoptive transfer of K/BxNsf PCs, but not K/BxN PCs, to K/BxN mice increased numbers of Tfh cells in draining lymph nodes. These results propose that abnormal accumulation of LLPCs in the spleen of autoimmune models drives the differentiation of autoantigen-primed CD4(+) T cells to Tfh cells. This positive feedback loop between splenic LLPCs and Tfh cells may contribute to the persistence of humoral autoimmunity. PMID:26729802

  1. Antibacterial plasma at safe levels for skin cells

    NASA Astrophysics Data System (ADS)

    Boekema, B. K. H. L.; Hofmann, S.; van Ham, B. J. T.; Bruggeman, P. J.; Middelkoop, E.

    2013-10-01

    Plasmas produce various reactive species, which are known to be very effective in killing bacteria. Plasma conditions, at which efficient bacterial inactivation is observed, are often not compatible with leaving human cells unharmed. The purpose of this study was to determine plasma settings for inactivation of Pseudomonas aeruginosa, without damaging skin cells in vitro under the same treatment conditions. An RF argon plasma jet excited with either continuous or time modulated (20 kHz, 20% duty cycle) voltages was used. To compare these two operation modes, only the input voltage was adjusted in order to obtain the same average power (1.7 W) for both modes. All other settings, i.e. gas flow, distance plasma tip to liquid surface, were kept constant. Bacteria or skin cells in physiological salt solution were exposed to direct non-contact plasma treatments. Short plasma treatments of up to 2 min resulted in a high reduction of bacterial numbers and did not affect dermal fibroblasts or keratinocytes. Bacterial inactivation has been previously ascribed to peroxynitrite, nitrite and H2O2 while eukaryotic cell viability is proposed to be reduced in the long term by the presence of H2O2 and is less affected by reactive nitrogen species. The remote RF plasma jet treatment was highly effective for bacterial inactivation while skin cell viability was preserved.

  2. Abnormal osteogenic and chondrogenic differentiation of human mesenchymal stem cells from patients with adolescent idiopathic scoliosis in response to melatonin

    PubMed Central

    Chen, Chong; Xu, Caixia; Zhou, Taifeng; Gao, Bo; Zhou, Hang; Chen, Changhua; Zhang, Changli; Huang, Dongsheng; Su, Peiqiang

    2016-01-01

    Abnormalities of membranous and endochondral ossification in patients with adolescent idiopathic scoliosis (AIS) remain incompletely understood. To investigate abnormalities in the melatonin signaling pathway and cellular response to melatonin in AIS, a case-control study of osteogenic and chondrogenic differentiation was performed using human mesenchymal stem cells (hMSCs). AIS was diagnosed by physical and radiographic examination. hMSCs were isolated from the bone marrow of patients with AIS and control subjects (n=12 each), and purified by density gradient centrifugation. The expression levels of melatonin receptors (MTs) 1 and 2 were detected by western blotting. Osteogenic and chondrogenic differentiation was induced by culturing hMSCs in osteogenic and chondrogenic media containing vehicle or 50 nM melatonin. Alkaline phosphatase (ALP) activity assays, quantitative glycosaminoglycan (GAG) analysis, and reverse transcription-quantitative polymerase chain reaction analysis were performed. Compared with controls, MT2 demonstrated low expression in the AIS group. Melatonin increased ALP activity, GAG synthesis and upregulated the expression of genes involved in osteogenic and chondrogenic differentiation including, ALP, osteopontin, osteocalcin, runt-related transcription factor 2, collagen type II, collagen type X, aggrecan and sex-determining region Y-box 9 in the normal control hMSCs, but did not affect the AIS groups. Thus, AIS hMSCs exhibit abnormal cellular responses to melatonin during osteogenic and chondrogenic differentiation, which may be associated with abnormal membranous and endochondral ossification, and skeletal growth. These results indicate a potential modulating role of melatonin via the MT2 receptor on abnormal osteogenic and chondrogenic differentiaation in patients with AIS. PMID:27314307

  3. Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells.

    PubMed

    Ryan, M C; Lee, K; Miyashita, Y; Carter, W G

    1999-06-14

    Laminin 5 regulates anchorage and motility of epithelial cells through integrins alpha6beta4 and alpha3beta1, respectively. We used targeted disruption of the LAMA3 gene, which encodes the alpha3 subunit of laminin 5 and other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in neonatal lethality, consistent with removal of all alpha3-laminin isoforms from epithelial BMs. Alterations in three different cellular functions were identified. First, using a novel tissue adhesion assay, we found that the mutant BM could not induce stable adhesion by integrin alpha6beta4, consistent with the presence of junctional blisters and abnormal hemidesmosomes. In the absence of laminin 5 function, we were able to detect a new ligand for integrin alpha3beta1 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin alpha3beta1 to interact with an alternative ligand. Second, we identified a survival defect in mutant epithelial cells that could be rescued by exogenous laminin 5, collagen, or an antibody against integrin alpha6beta4, suggesting that signaling through beta1 or beta4 integrins is sufficient for survival. Third, we detected abnormalities in ameloblast differentiation in developing mutant incisors indicating that events downstream of adhesion are affected in mutant animals. These results indicate that laminin 5 has an important role in regulating tissue organization, gene expression, and survival of epithelium. PMID:10366601

  4. Plasma cell toll-like receptor (TLR) expression differs from that of B cells, and plasma cell TLR triggering enhances immunoglobulin production.

    PubMed

    Dorner, Marcus; Brandt, Simone; Tinguely, Marianne; Zucol, Franziska; Bourquin, Jean-Pierre; Zauner, Ludwig; Berger, Christoph; Bernasconi, Michele; Speck, Roberto F; Nadal, David

    2009-12-01

    Toll-like receptors (TLRs) are key receptors of the innate immune system and show cell subset-specific expression. We investigated the messenger RNA (mRNA) expression of TLR genes in human haematopoietic stem cells (HSC), in naïve B cells, in memory B cells, in plasma cells from palatine tonsils and in plasma cells from peripheral blood. HSC and plasma cells showed unrestricted expression of TLR1-TLR9, in contrast to B cells which lacked TLR3, TLR4 and TLR8 but expressed mRNA of all other TLRs. We demonstrated, for the first time, that TLR triggering of terminally differentiated plasma cells augments immunoglobulin production. Thus, boosting the immediate antibody response by plasma cells upon pathogen recognition may point to a novel role of TLRs. PMID:19950420

  5. Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT.

    PubMed

    Marchand, Lucas S; St-Hilaire, Sophie; Putnam, Elizabeth A; Serve, Kinta M; Pfau, Jean C

    2012-01-25

    Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p=0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects (p=0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease. PMID:22085844

  6. Plasma needle: treatment of living cells and tissues

    NASA Astrophysics Data System (ADS)

    Stoffels, Eva

    2003-10-01

    Non-thermal plasmas are capable of refined treatment of heat sensitive surfaces. Recently, many non-thermal sources working under atmospheric pressure have been constructed. Their main applications are various surface treatments: cleaning, etching, changing the wettability/adhesion, and bacterial decontamination. A new research at the Eindhoven University of Technology focuses on in vivo treatment by means of a novel non-thermal plasma source (the plasma needle). At present, a fundamental study has been undertaken to identify all possible responses of living objects exposed to the plasma. Plasma treatment does not lead to cell death (necrosis), which is a cause of inflammation. On the contrary, we observe various sophisticated reactions of mammalian cells, e.g. cell detachment (loss of cell contact) and programmed cell death (apoptosis). Moreover, under certain conditions the plasma is capable of killing bacteria, while eukaryotic cells remain unharmed. These findings may result in development of new techniques, like bacterial sterilization of infected (living) tissues or removal of cells without inflammatory response, and on a longer time scale to new methods in the health care. Possible applications include treatment of skin ailments, aiding wound healing and sterilization of dental cavities.

  7. Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid.

    PubMed

    Gómez-Meda, B C; Zamora-Perez, A L; Muñoz-Magallanes, T; Sánchez-Parada, M G; García Bañuelos, J J; Guerrero-Velázquez, C; Sánchez-Orozco, L V; Vera-Cruz, J M; Armendáriz-Borunda, J; Zúñiga-González, G M

    2016-02-01

    Diabetes mellitus (DM) is characterized by high blood glucose. Excessive production of free radicals may cause oxidative damage to DNA and other molecules, leading to complications of the disease. It may be possible to delay or reduce such damage by administration of antioxidants such as folic acid (FA). The objective of this study was to determine the effect of FA on nuclear abnormalities (NAs) in the oral mucosa of patients with DM. NAs (micronucleated cells, binucleated cells, pyknotic nuclei, karyorrhexis, karyolysis, abnormally condensed chromatin, and nuclear buds) were analyzed in 2000 cells from 45 healthy individuals (control group) and 55 patients with controlled or uncontrolled type I or II DM; 35 patients in the latter group were treated with FA. Samples were taken from the FA group before and after treatment. An increased rate of NAs was found in patients with DM in comparison with that of the control group (P<0.001). FA supplementation in patients with DM reduced the frequency of NAs (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment; P<0.001). The type I and type II DM and controlled and uncontrolled DM subgroups were analyzed in terms of sex, age, and smoking habit. The significantly reduced frequencies of buccal mucosa cells with micronuclei, binucleation, pyknosis, karyorrhexis, karyorrhexis+abnormally condensed chromatin, karyolysis, and nuclear buds produced by FA supplementation in DM patients (P<0.02) are consistent with the idea that free radicals are responsible for the increased frequency of NAs in DM patients. PMID:26921015

  8. General Information about Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  9. Epidemiology of the plasma-cell disorders.

    PubMed

    Kyle, Robert A; Rajkumar, S Vincent

    2007-12-01

    This review of the plasma-cell disorders begins with the definition of monoclonal gammopathy of undetermined significance (MGUS). The prevalence of MGUS in white and black populations is described. MGUS is a common finding in the medical practice of all physicians, and thus it is important to both the patient and the physician to determine whether the monoclonal protein remains stable or progresses to multiple myeloma (MM), Waldenström's macroglobulinemia (WM), primary systemic amyloidosis (AL), or a related disorder. The long-term (almost 40 years) follow-up data of 241 patients in the Mayo Clinic population is provided. In a large study of 1384 patients with MGUS from southeastern Minnesota, the risk of progression to MM, WM, AL, or other disorders was approximately 1% per year. Risk factors for progression are provided. The incidence of MM in Olmsted County, Minnesota, remained stable for the 56-year span 1945-2001. The apparent increase in incidence and mortality rates among patients with MM in many studies is due to improved case ascertainment, especially among the elderly. The incidence and mortality rates of MM in the United States and other countries are presented. The major emphasis is on the cause of MM, which is unclear. Exposure to radiation from atomic bombs, therapeutic and diagnostic radiation, and in workers in the nuclear industry field are addressed. Many studies involving agricultural occupations, exposure to benzene, petroleum products, and engine exhaust and other industrial exposures are discussed. Tobacco use, obesity, diet, and alcohol ingestion are all possible causes of MM. Clusters of MM have been noted. Multiple cases of MM have been found in first-degree relatives. PMID:18070711

  10. Plasma Cell Mucositis of Oro- and Hypopharynx: A Case Report

    PubMed Central

    Puvanendran, Mark; Lieder, Anja; Issing, Wolfgang

    2012-01-01

    Objective. To raise awareness of plasma cell mucositis as a rare differential diagnosis for oral mucosal ulceration and its macroscopic similarity to malignancy. Method. We report a patient who presented with oral features suggestive of malignancy. A biopsy revealed plasma cell mucositis. Results. The patient successfully had a full excision of one lesion and a spontaneous resolution of the other. Conclusion. With the increasing incidence of oral mucosal pathology, physicians should be aware of this differential diagnosis. PMID:22953106

  11. Primary Plasma Cell Leukemia: Identity Card 2016.

    PubMed

    Musto, Pellegrino; Simeon, Vittorio; Todoerti, Katia; Neri, Antonino

    2016-04-01

    Primary plasma cell leukemia (PPCL) is an aggressive and rare variant of multiple myeloma (MM), characterized by peculiar adverse clinical and biological features. Though the poor outcome of PPCL has been slightly improved by novel treatments during the last 10 years, due to the limited number of available studies in this uncommon disease, optimal therapy remains a classic unmet clinical need. Anyway, in the real-life practice, induction with a bortezomib-based three-drug combination, including dexamethasone and, possibly, lenalidomide, or, alternatively, thalidomide, cyclophosphamide, or doxorubicin, is a reasonable first-line option. This approach may be particularly advisable for patients with adverse cytogenetics, hyperleucocytosis, and rapidly progressive disease, in whom a fast response is required, or for those with suboptimal renal function, where, however, lenalidomide should be used with caution until renal activity is restored. In younger subjects, leukemia/lymphoma-like more intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone or continue-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide, may be also combined with bortezomib +/- thalidomide. Treatment must be started immediately after a diagnosis of PPCL is made to avoid the risk of irreversible disease complications and, in such a context, the prevention of tumor lysis syndrome is mandatory. In patients eligible for autologous stem cell transplantation (AuSCT), other alkylating agents, in particular melphalan, should be initially avoided in order to allow adequate collections of CD34+ peripheral blood stem cells (PBSC). A combination of lenalidomide and dexamethasone may be a valuable alternative option to manage older or unfit patients or those with slower disease evolution or with signs of neuropathy, contraindicating the use of bortezomib. Patients not suitable for transplant procedures should continue the treatment, if a

  12. [Research on cells ablation characters by laser plasma].

    PubMed

    Han, Jing-hua; Zhang, Xin-gang; Cai, Xiao-tang; Duan, Tao; Feng, Guo-ying; Yang, Li-ming; Zhang, Ya-jun; Wang, Shao-peng; Li, Shi-wen

    2012-08-01

    The study on the mechanism of laser ablated cells is of importance to laser surgery and killing harmful cells. Three radiation modes were researched on the ablation characteristics of onion epidermal cells under: laser direct irradiation, focused irradiation and the laser plasma radiation. Based on the thermodynamic properties of the laser irradiation, the cell temperature rise and phase change have been analyzed. The experiments show that the cells damage under direct irradiation is not obvious at all, but the focused irradiation can cause cells to split and moisture removal. The removal shape is circular with larger area and rough fracture edges. The theoretical analysis found out that the laser plasma effects play a key role in the laser ablation. The thermal effects, radiation ionization and shock waves can increase the deposition of laser pulses energy and impact peeling of the cells, which will greatly increase the scope and efficiency of cell killing and is suitable for the cell destruction. PMID:23156745

  13. Effects of Non-Thermal Plasma on Mammalian Cells

    PubMed Central

    Kalghatgi, Sameer; Kelly, Crystal M.; Cerchar, Ekaterina; Torabi, Behzad; Alekseev, Oleg; Fridman, Alexander; Friedman, Gary; Azizkhan-Clifford, Jane

    2011-01-01

    Thermal plasmas and lasers have been widely used in medicine to cut, ablate and cauterize tissues through heating; in contrast, non-thermal plasma produces no heat, so its effects can be selective. In order to exploit the potential for clinical applications, including wound healing, sterilization, blood coagulation, and cancer treatment, a mechanistic understanding of the interaction of non-thermal plasma with living tissues is required. Using mammalian cells in culture, it is shown here that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects that range from increasing cell proliferation to inducing apoptosis. It is also shown that these effects are primarily due to formation of intracellular reactive oxygen species (ROS). We have utilized γ-H2AX to detect DNA damage induced by non-thermal plasma and found that it is initiated by production of active neutral species that most likely induce formation of organic peroxides in cell medium. Phosphorylation of H2AX following non-thermal plasma treatment is ATR dependent and ATM independent, suggesting that plasma treatment may lead to replication arrest or formation of single-stranded DNA breaks; however, plasma does not lead to formation of bulky adducts/thymine dimers. PMID:21283714

  14. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  15. Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome.

    PubMed

    Zhang, Xuan; Dai, Rongxin; Li, Wenyan; Zhao, Hongyi; Zhang, Yongjie; Zhou, Lina; Du, Hongqiang; Luo, Guangjin; Wu, Junfeng; Niu, Linlin; An, Yunfei; Zhang, Zhiyong; Ding, Yuan; Song, Wenxia; Liu, Chaohong; Zhao, Xiaodong

    2016-06-23

    Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4(+) T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6(+) Tfh cells, but the frequency of ICOS(+) Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS(+) Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS(+) Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4(+) naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6. PMID:27170596

  16. Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome

    PubMed Central

    Zhang, Xuan; Dai, Rongxin; Li, Wenyan; Zhao, Hongyi; Zhang, Yongjie; Zhou, Lina; Du, Hongqiang; Luo, Guangjin; Wu, Junfeng; Niu, Linlin; An, Yunfei; Zhang, Zhiyong; Ding, Yuan; Song, Wenxia; Liu, Chaohong

    2016-01-01

    Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific regulator of actin nucleation. Wiskott-Aldrich syndrome (WAS) patients show immunodeficiencies, most of which have been attributed to defective T-cell functions. T follicular helper (Tfh) cells are the major CD4+ T-cell subset with specialized B-cell helper capabilities. Aberrant Tfh cells activities are involved in immunopathologies such as autoimmunity, immunodeficiencies, and lymphomas. We found that in WAS patients, the number of circulating Tfh cells was significantly reduced due to reduced proliferation and increased apoptosis, and Tfh cells were Th2 and Th17 polarized. The expression of inducible costimulator (ICOS) in circulating Tfh cells was higher in WAS patients than in controls. BCL6 expression was decreased in total CD4+ T and Tfh cells of WAS patients. Mirroring the results in patients, the frequency of Tfh cells in WAS knockout (KO) mice was decreased, as was the frequency of BCL6+ Tfh cells, but the frequency of ICOS+ Tfh cells was increased. Using WAS chimera mice, we found that the number of ICOS+ Tfh cells was decreased in WAS chimera mice, indicating that the increase in ICOS+ Tfh cells in WAS KO mice was cell extrinsic. The data from in vivo CD4+ naive T-cell adoptive transfer mice as well as in vitro coculture of naive B and Tfh cells showed that the defective function of WASp-deficient Tfh cells was T-cell intrinsic. Consistent findings in both WAS patients and WAS KO mice suggested an essential role for WASp in the development and memory response of Tfh cells and that WASp deficiency causes a deficient differentiation defect in Tfh cells by downregulating the transcription level of BCL6. PMID:27170596

  17. Red Blood Cells from Individuals with Abdominal Obesity or Metabolic Abnormalities Exhibit Less Deformability upon Entering a Constriction

    PubMed Central

    Zeng, Nancy F.; Mancuso, Jordan E.; Zivkovic, Angela M.; Smilowitz, Jennifer T.; Ristenpart, William D.

    2016-01-01

    Abdominal obesity and metabolic syndrome (MS) are multifactorial conditions associated with increased risk of cardiovascular disease and type II diabetes mellitus. Previous work has demonstrated that the hemorheological profile is altered in patients with abdominal obesity and MS, as evidenced for example by increased whole blood viscosity. To date, however, no studies have examined red blood cell (RBC) deformability of blood from individuals with obesity or metabolic abnormalities under typical physiological flow conditions. In this study, we pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the mechanical behavior of ~8,000 RBCs obtained from either healthy individuals (n = 5) or obese participants with metabolic abnormalities (OMA) (n = 4). We demonstrate that the OMA+ cells stretched on average about 25% less than the healthy controls. Furthermore, we examined the effects of ingesting a high-fat meal on RBC mechanical dynamics, and found that the postprandial period has only a weak effect on the stretching dynamics exhibited by OMA+ cells. The results suggest that chronic rigidification of RBCs plays a key role in the increased blood pressure and increased whole blood viscosity observed in OMA individuals and was independent of an acute response triggered by consumption of a high-fat meal. Trial Registration ClinicalTrials.gov NCT01803633 PMID:27258098

  18. Fluid shear stress as a regulator of gene expression in vascular cells: possible correlations with diabetic abnormalities

    NASA Technical Reports Server (NTRS)

    Papadaki, M.; Eskin, S. G.; Ruef, J.; Runge, M. S.; McIntire, L. V.

    1999-01-01

    Diabetes mellitus is associated with increased frequency, severity and more rapid progression of cardiovascular diseases. Metabolic perturbations from hyperglycemia result in disturbed endothelium-dependent relaxation, activation of coagulation pathways, depressed fibrinolysis, and other abnormalities in vascular homeostasis. Atherosclerosis is localized mainly at areas of geometric irregularity at which blood vessels branch, curve and change diameter, and where blood is subjected to sudden changes in velocity and/or direction of flow. Shear stress resulting from blood flow is a well known modulator of vascular cell function. This paper presents what is currently known regarding the molecular mechanisms responsible for signal transduction and gene regulation in vascular cells exposed to shear stress. Considering the importance of the hemodynamic environment of vascular cells might be vital to increasing our understanding of diabetes.

  19. In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons.

    PubMed

    Thomas, Elizabeth A; Coppola, Giovanni; Tang, Bin; Kuhn, Alexandre; Kim, SoongHo; Geschwind, Daniel H; Brown, Timothy B; Luthi-Carter, Ruth; Ehrlich, Michelle E

    2011-03-15

    Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared with those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support. While genes related to excitotoxicity, dopamine signaling and trophic support were altered in both DE5 and R6/2 mice, which may be either cell autonomous or non-cell autonomous, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell-autonomous mechanisms. Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt, in the absence of expression in cortical neurons. PMID:21177255

  20. Biomedical Applications of the Cold Atmospheric Plasma: Cell Responses

    NASA Astrophysics Data System (ADS)

    Volotskova, Olga

    Current breakthrough research on cold atmospheric plasma (CAP) demonstrates that CAP has great potential in various areas, including medicine and biology, thus providing a new tool for living tissue treatment. Depending on the configuration the cold plasma sources can be used in the following areas: wound healing, skin diseases, hospital hygiene, sterilization, antifungal treatments, dental care, cosmetics targeted cell/tissue removal, and cancer treatments. This dissertation is focused on the studies of biomedical applications of cold atmospheric plasma jet based on helium flow and resultant cell responses to the cold plasma treatment. The studies were carried out on extra-cellular and intra-cellular levels in vitro. The main practical applications are wound healing and alternative to existing cancer therapy methods, areas of great interest and significant challenges. The CAP jet was built in the Micropropulsion and Nanotechnology Laboratory of Dr. Michael Keidar, as a part of multidisciplinary collaboration with the GW Medical School (Dr. M.A. Stepp) concerned with plasma medicine and bioengineering studies. Normal and cancer cells have two fundamental behavioral properties, proliferation and motility, which can be evaluated through cell migration rates and cell cycle progression. Various microscopic, spectroscopic and flow cytometry techniques were used to characterize cell responses to the cold plasma treatment. It was found that CAP effect on the cells is localized within the area of the treatment (of around ˜ 5mm in diameter). The migration rates of the normal skin cells can be reduced up to ˜ 40%. However, depending on the cell type the required treatment time is different, thus differential treatment of various cells presented in tissue is possible. The CAP effect on the migration was explained through the changes of the cell surface proteins/integrins. It was also found that normal and cancer cells respond differently to the CAP treatment under the same

  1. Abnormal expression of PTEN and PIK3CA in pemetrexed-resistant human pancreatic cancer cell line Patu8988.

    PubMed

    Shi, X; Gu, H T; Lin, S B; Zhang, Y; Yang, J; Qian, C J

    2016-01-01

    The aim of this study was to investigate the expression of PTEN and PIK3CA in the pemetrexed-resistant human pancreatic cancer cell line Patu8988, and to evaluate their effects on the biological behavior of pancreatic cancer cells. PTEN and PIK3CA gene and protein expressions were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively, in a pemetrexed-resistant pancreatic cancer cell line and in the parent strain of the pancreatic cancer cells. The discrepancies between the two types of cell lines were detected by a transwell test. RT-PCR and western blot analyses revealed that PTEN and PIK3CA were overexpressed in the pemetrexed-resistant pancreatic cancer cell line. PTEN and PIK3CA were shown to be upregulated by 89 and 76% (western blot), respectively, in the pemetrexed-resistant cell line, compared to the normal pancreatic cancer cell line. The migratory and invasive abilities of the pemetrexed-resistant pancreatic cancer cell were significantly reduced compared to those of the parent strain (P < 0.05; transwell assay). Both PTEN and PIK3CA expression was abnormally enhanced in the pemetrexed-resistant cell line Patu8988; the co-existence of high levels of PTEN and PIK3CA in the pemetrexed-resistant pancreatic cancer line cells induced a significant decrease in their migratory and invasive capacities. This suggested that the mechanism of pemetrexed resistant may be affected by PTEN and PIK3CA, and that these may alter the biological behavior of cancer cells. PMID:27525871

  2. Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents

    SciTech Connect

    Jaspers, N.G.; de Wit, J.; Regulski, M.R.; Bootsma, D.

    1982-01-01

    The effect of different carcinogenic agents on the rate of semiconservative DNA replication in normal and ataxia telangiectasis (AT) cells was investigated. The rate of DNA synthesis in all AT cell strains tested was depressed to a significantly lesser extent than in normal cells after exposure to X-rays under oxia or hypoxia or to bleomycin, agents to which AT cells are hypersensitive. In contrast, inhibition of DNA replication in normal human and AT cells was similar after treatment with some DNA-methylating agents or mitomycin C. Colony-forming ability of AT cells treated with these agents was not different from normal cells. Treatment with 4-nitroquinoline 1-oxide elicited a variable response in both AT and normal cell strains. In some strains, including those shown to be hypersensitive to the drug by other workers, the inhibition of DNA synthesis was more pronounced than in other cell strains, but no significant difference between AT and normal cells could be detected. The rejoining of DNA strand breaks induced by X-rays, measured by DNA elution techniques, occurred within l2 hr after treatment and could not be correlated with the difference in DNA synthesis inhibition in AT and normal cells. After low doses of X-rays, AT cells rejoined single-strand breaks slightly more slowly than did normal cells. The rate of DNA replication in X-irradiation AT and normal cells was not affected by nicotinamide, an inhibitor of poly(adenosine diphosphate ribose) synthesis. These data indicate that the diminished inhibition of DNA replication in carcinogen-treated AT cells (a) is a general characteristic of all AT cell strains, (b) correlates with AT cellular hypersensitivity, (c) is not directly caused by the bulk of the DNA strand breaks produced by carcinogenic agents, and (d) is not based on differences in the induction of poly(adenosine diphosphate ribose) synthesis between X-irradiated AT and normal cells.

  3. Plasma cell myeloma--new biological insights and advances in therapy.

    PubMed

    Barlogie, B; Epstein, J; Selvanayagam, P; Alexanian, R

    1989-03-01

    Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with "LDH phenotype," which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M

  4. Low Temperature Plasma Kills SCaBER Cancer Cells

    NASA Astrophysics Data System (ADS)

    Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

    2013-09-01

    Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

  5. Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Li, Shu-Ping; Su, Hong-Xin; Zhao, Da; Guan, Quan-Lin

    2016-01-01

    Background MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). Material/Methods We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. Results Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. Conclusions miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC. PMID:27345473

  6. Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma.

    PubMed

    Li, Shu-Ping; Su, Hong-Xin; Zhao, Da; Guan, Quan-Lin

    2016-01-01

    BACKGROUND MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. RESULTS Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P<0.001). The expression of miRNA-506 in the plasma was closely associated with lymph node status (P=0.004), TNM stage (P=0.031), and tumor length (P<0.001). According to ROC curves, the area under the curve for plasma miRNA-506 was 0.835, indicating statistical significance for ESCC diagnosis by plasma miRNA-506 (P<0.001). Kaplan-Meier analysis showed that patients with high miRNA-506 expression had significantly shorter survival time than those with low miRNA-506 expression. Cox regression analysis demonstrated that T stage, N stage, tumor length, and miRNA-506 expression levels were significantly correlated with prognosis in ESCC patients. CONCLUSIONS miRNA-506 can serve as an important molecular marker for diagnosis and prognostic prediction of ESCC. PMID:27345473

  7. New insights into CD4(+) T cell abnormalities in systemic sclerosis.

    PubMed

    Liu, Mengguo; Wu, Wenyu; Sun, Xinfen; Yang, Ji; Xu, Jinhua; Fu, Wenwen; Li, Ming

    2016-04-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by vasculopathy and excessive deposition of extracellular matrix, which causes fibrosis of the skin and internal organs and eventually leads to multiorgan dysfunction. Studies have shown that CD4(+) T cell activation is a key factor in the pathogenesis of scleroderma because activated T cells can release various cytokines, resulting in inflammation, microvascular damage and fibrosis. T helper cell 17 (Th17) and regulatory T (Treg) cell activities are a hallmark SSc, as Th17-type cytokines can induce both inflammation and fibrosis. More recently, several studies have reported new T cell subsets, including Th9 and Th22 cells, along with their respective cytokines in the peripheral blood, serum and skin lesions of individuals with SSc. Herein, we review recent data on various CD4(+) T helper cell subsets in SSc, and discuss potential roles of these cells in promoting inflammation and fibrosis. PMID:26724976

  8. Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus.

    PubMed

    Krishnan, Sandeep; Nambiar, Madhusoodana P; Warke, Vishal G; Fisher, Carolyn U; Mitchell, Jeanne; Delaney, Nancy; Tsokos, George C

    2004-06-15

    In response to appropriate stimulation, T lymphocytes from systemic lupus erythematosus (SLE) patients exhibit increased and faster intracellular tyrosine phosphorylation and free calcium responses. We have explored whether the composition and dynamics of lipid rafts are responsible for the abnormal T cell responses in SLE. SLE T cells generate and possess higher amounts of ganglioside-containing lipid rafts and, unlike normal T cells, SLE T cell lipid rafts include FcRgamma and activated Syk kinase. IgM anti-CD3 Ab-mediated capping of TCR complexes occurs more rapidly in SLE T cells and concomitant with dramatic acceleration of actin polymerization kinetics. The significance of these findings is evident from the observation that cross-linking of lipid rafts evokes earlier and higher calcium responses in SLE T cells. Thus, we propose that alterations in the lipid raft signaling machinery represent an important mechanism that is responsible for the heightened and accelerated T cell responses in SLE. PMID:15187166

  9. B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events.

    PubMed Central

    Liossis, S N; Kovacs, B; Dennis, G; Kammer, G M; Tsokos, G C

    1996-01-01

    To understand the molecular mechanisms that are responsible for the B cell overactivity that is observed in patients with SLE, we have conducted experiments in which the surface immunoglobulin (sIg)-mediated early cell signaling events were studied. The anti-sIgM-mediated free intracytoplasmic calcium ([Ca2+]i) responses were significantly higher in SLE B cells compared with responses of normal individuals and to those of patients with other systemic autoimmune rheumatic diseases. The anti-IgD mAb induced [Ca2+]i responses were also higher in lupus B cells than in controls. The magnitude of anti-sIgM-mediated Ca2+ release from intracellular stores was also increased in B cells from SLE patients compared with normal controls. The amount of inositol phosphate metabolites produced upon crosslinking of sIgM was slightly higher in patients with lupus than in normal controls, although the difference was not statistically significant. In contrast, the degree of anti-sIgM-induced protein tyrosine phosphorylation was obviously increased in lupus patients. Our study demonstrates clearly for the first time that SLE B cells exhibit aberrant early signal transduction events, including augmented calcium responses after crosslinking of the B cell receptor and increased antigen-receptor-mediated phosphorylation of protein tyrosine residues. Because the above abnormalities did not correlate with disease activity or treatment status, we propose that they may have pathogenic significance. PMID:8958217

  10. Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

    PubMed

    Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

    2016-04-01

    Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. PMID:26808221

  11. Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

    PubMed

    Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

    2016-01-01

    Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

  12. Predicting hydrogen isotope inventory in plasma-facing components during normal and abnormal operations in fusion devices

    NASA Astrophysics Data System (ADS)

    Hu, Alice; Hassanein, Ahmed

    2015-10-01

    Hydrogen isotope behavior and inventory in plasma-facing components (PFCs) of fusion devices are key concerns for safe, reliable, and economical operation. To accurately estimate hydrogen isotope retention and recovery in tungsten (the current leading candidate as a PFC), we have developed a model that was recently benchmarked against isotope depth profile and retention level in a tungsten target under various conditions and compared with both experimental data and simulation results. In this research, we have extended the model to include details of transient events. Therefore, one can use this model to estimate hydrogen isotope retention behavior in tungsten and potential other PFC candidates during normal operational pulse, effects of edge-localized modes (ELMs), and a possible cleaning processes scenario.

  13. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  14. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  15. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  16. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  17. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  18. Junctional abnormalities in human airway epithelial cells expressing F508del CFTR

    PubMed Central

    Stauffer, Brandon; Moriarty, Hannah K.; Kim, Agnes H.; McCarty, Nael A.; Koval, Michael

    2015-01-01

    Cystic fibrosis (CF) has a profound impact on airway physiology. Accumulating evidence suggests that intercellular junctions are impaired in CF. We examined changes to CF transmembrane conductance regulator (CFTR) function, tight junctions, and gap junctions in NuLi-1 (CFTRwt/wt) and CuFi-5 (CFTRΔF508/ΔF508) cells. Cells were studied at air-liquid interface (ALI) and compared with primary human bronchial epithelial cells. On the basis of fluorescent lectin binding, the phenotype of the NuLi-1 and CuFi-5 cells at week 8 resembled that of serous, glycoprotein-rich airway cells. After week 7, CuFi-5 cells possessed 130% of the epithelial Na+ channel activity and 17% of the CFTR activity of NuLi-1 cells. In both cell types, expression levels of CFTR were comparable to those in primary airway epithelia. Transepithelial resistance of NuLi-1 and CuFi-5 cells stabilized during maturation in ALI culture, with significantly lower transepithelial resistance for CuFi-5 than NuLi-1 cells. We also found that F508del CFTR negatively affects gap junction function in the airway. NuLi-1 and CuFi-5 cells express the connexins Cx43 and Cx26. While both connexins were properly trafficked by NuLi-1 cells, Cx43 was mistrafficked by CuFi-5 cells. Cx43 trafficking was rescued in CuFi-5 cells treated with 4-phenylbutyric acid (4-PBA), as assessed by intracellular dye transfer. 4-PBA-treated CuFi-5 cells also exhibited an increase in forskolin-induced CFTR-mediated currents. The Cx43 trafficking defect was confirmed using IB3-1 cells and found to be corrected by 4-PBA treatment. These data support the use of NuLi-1 and CuFi-5 cells to examine the effects of F508del CFTR expression on tight junction and gap junction function in the context of serous human airway cells. PMID:26115671

  19. Junctional abnormalities in human airway epithelial cells expressing F508del CFTR.

    PubMed

    Molina, Samuel A; Stauffer, Brandon; Moriarty, Hannah K; Kim, Agnes H; McCarty, Nael A; Koval, Michael

    2015-09-01

    Cystic fibrosis (CF) has a profound impact on airway physiology. Accumulating evidence suggests that intercellular junctions are impaired in CF. We examined changes to CF transmembrane conductance regulator (CFTR) function, tight junctions, and gap junctions in NuLi-1 (CFTR(wt/wt)) and CuFi-5 (CFTR(ΔF508/ΔF508)) cells. Cells were studied at air-liquid interface (ALI) and compared with primary human bronchial epithelial cells. On the basis of fluorescent lectin binding, the phenotype of the NuLi-1 and CuFi-5 cells at week 8 resembled that of serous, glycoprotein-rich airway cells. After week 7, CuFi-5 cells possessed 130% of the epithelial Na(+) channel activity and 17% of the CFTR activity of NuLi-1 cells. In both cell types, expression levels of CFTR were comparable to those in primary airway epithelia. Transepithelial resistance of NuLi-1 and CuFi-5 cells stabilized during maturation in ALI culture, with significantly lower transepithelial resistance for CuFi-5 than NuLi-1 cells. We also found that F508del CFTR negatively affects gap junction function in the airway. NuLi-1 and CuFi-5 cells express the connexins Cx43 and Cx26. While both connexins were properly trafficked by NuLi-1 cells, Cx43 was mistrafficked by CuFi-5 cells. Cx43 trafficking was rescued in CuFi-5 cells treated with 4-phenylbutyric acid (4-PBA), as assessed by intracellular dye transfer. 4-PBA-treated CuFi-5 cells also exhibited an increase in forskolin-induced CFTR-mediated currents. The Cx43 trafficking defect was confirmed using IB3-1 cells and found to be corrected by 4-PBA treatment. These data support the use of NuLi-1 and CuFi-5 cells to examine the effects of F508del CFTR expression on tight junction and gap junction function in the context of serous human airway cells. PMID:26115671

  20. In-situ observation of abnormal electron temperure in the F-region valley associated with the prereversal enhancement in the vertical plasma drift

    NASA Astrophysics Data System (ADS)

    Muralikrishna, Polinaya; Batista, Inez S.; Odriozola, Siomel

    During one of the post sunset rocket launches made on 18-th December 1995 from the equatorial rocket launching station CLA in Alcântara, Brazil a Langmuir probe measured abnormally large electron temperatures below the F-region just before the onset of plasma bubbles but temperatures became normal soon after the onset of bubbles. In-situ measurements made from Brazil recently using rocket-borne swept-bias Langmuir Probes show that the electron temperatures in the valley region between the equatorial E and F regions get modified before the onset of plasma bubbles, probably associated with the prereversal enhancement in the vertical plasma drift. On 2-nd December 2011 a Brazilian VS-30 single stage rocket was launched from the equatorial rocket launching station CLBI in Natal, Brazil carrying a Langmuir probe operating alternately in swept and constant bias modes to measure both electron temperature and electron density respectively. The ground equipments operated during the rocket launch clearly showed the rapid rise of the F-region base indicating the prereversal enhancement of the F-region vertical drift. At the time of launch the bubble activity was also at its peak. The electron density and temperature height profiles could be estimated from the LP data up to the rocket apogee altitude of 139km. During the rocket upleg and downleg the valley region showed the presence of electron temperatures as high as 2000 ºK while the temperatures expected from the existing models are around 500 ºK. A two stage VS-30/Orion rocket was again launched on 8-th December 2012 soon after sunset carrying a Langmuir Probe operating alternately in swept and constant bias modes. At the time of launch ground equipments operated at equatorial stations showed rapid rise in the base of the F-layer and creating ionospheric conditions favorable for the generation of plasma bubbles. Electron temperatures as high as 3500ºK were observed in the valley region during the rocket upleg and

  1. Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

    SciTech Connect

    Baconnais, S.; Delavoie, F. |; Zahm, J.M.; Milliot, M.; Castillon, N.; Terryn, C.; Banchet, V.; Michel, J.; Danos, O.; Merten, M.; Chinet, T.; Zierold, K.; Bonnet, N.; Puchelle, E. , E-Mail: edith.puchelle@univ-reims.fr; Balossier, G.

    2005-10-01

    The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na{sup +} absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na{sup +}, Mg{sup 2+}, P, S and Cl{sup -}) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR{sub inh}-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

  2. Electromagnetic ''particle-in-cell'' plasma simulation

    SciTech Connect

    Langdon, A.B.

    1985-04-22

    ''PIC'' simulation tracks particles through electromagnetic fields calculated self-consistently from the charge and current densities of the particles themselves, external sources, and boundaries. Already used extensively in plasma physics, such simulations have become useful in the design of accelerators and their r.f. sources. 5 refs.

  3. NKCC1-Deficiency Results in Abnormal Proliferation of Neural Progenitor Cells of the Lateral Ganglionic Eminence.

    PubMed

    Magalhães, Ana Cathia; Rivera, Claudio

    2016-01-01

    The proliferative pool of neural progenitor cells is maintained by exquisitely controlled mechanisms for cell cycle regulation. The Na-K-Cl cotransporter (NKCC1) is important for regulating cell volume and the proliferation of different cell types in vitro. NKCC1 is expressed in ventral telencephalon of embryonic brains suggesting a potential role in neural development of this region. The ventral telencephalon is a major source for both interneuron and oligodendrocyte precursor cells. Whether NKCC1 is involved in the proliferation of these cell populations remains unknown. In order to assess this question, we monitored several markers for neural, neuronal, and proliferating cells in wild-type (WT) and NKCC1 knockout (KO) mouse brains. We found that NKCC1 was expressed in neural progenitor cells from the lateral ganglionic eminence (LGE) at E12.5. Mice lacking NKCC1 expression displayed reduced phospho-Histone H3 (PH3)-labeled mitotic cells in the ventricular zone (VZ) and reduced cell cycle reentry. Accordingly, we found a significant reduction of Sp8-labeled immature interneurons migrating from the dorsal LGE in NKCC1-deficient mice at a later developmental stage. Interestingly, at E14.5, NKCC1 regulated also the formation of Olig2-labeled oligodendrocyte precursor cells. Collectively, these findings show that NKCC1 serves in vivo as a modulator of the cell cycle decision in the developing ventral telencephalon at the early stage of neurogenesis. These results present a novel mechanistic avenue to be considered in the recent proposed involvement of chloride transporters in a number of developmentally related diseases, such as epilepsy, autism, and schizophrenia. PMID:27582690

  4. NKCC1-Deficiency Results in Abnormal Proliferation of Neural Progenitor Cells of the Lateral Ganglionic Eminence

    PubMed Central

    Magalhães, Ana Cathia; Rivera, Claudio

    2016-01-01

    The proliferative pool of neural progenitor cells is maintained by exquisitely controlled mechanisms for cell cycle regulation. The Na-K-Cl cotransporter (NKCC1) is important for regulating cell volume and the proliferation of different cell types in vitro. NKCC1 is expressed in ventral telencephalon of embryonic brains suggesting a potential role in neural development of this region. The ventral telencephalon is a major source for both interneuron and oligodendrocyte precursor cells. Whether NKCC1 is involved in the proliferation of these cell populations remains unknown. In order to assess this question, we monitored several markers for neural, neuronal, and proliferating cells in wild-type (WT) and NKCC1 knockout (KO) mouse brains. We found that NKCC1 was expressed in neural progenitor cells from the lateral ganglionic eminence (LGE) at E12.5. Mice lacking NKCC1 expression displayed reduced phospho-Histone H3 (PH3)-labeled mitotic cells in the ventricular zone (VZ) and reduced cell cycle reentry. Accordingly, we found a significant reduction of Sp8-labeled immature interneurons migrating from the dorsal LGE in NKCC1-deficient mice at a later developmental stage. Interestingly, at E14.5, NKCC1 regulated also the formation of Olig2-labeled oligodendrocyte precursor cells. Collectively, these findings show that NKCC1 serves in vivo as a modulator of the cell cycle decision in the developing ventral telencephalon at the early stage of neurogenesis. These results present a novel mechanistic avenue to be considered in the recent proposed involvement of chloride transporters in a number of developmentally related diseases, such as epilepsy, autism, and schizophrenia. PMID:27582690

  5. Arcing of negatively biased solar cells in a plasma environment

    NASA Astrophysics Data System (ADS)

    Upschulte, B. L.; Marinelli, W. J.; Carleton, K. L.; Weyl, G.; Aifer, E.; Hastings, D. E.

    1994-05-01

    Experimental and theoretical efforts have been conducted to investigate the arcing of negatively biased solar arrays in a low-Earth orbit plasma environment. Experiments were conducted in an ultrahigh vacuum plasma test chamber, where the environment could be controlled carefully. Outgassing of the adhesive used to bind the protective coverglass to the solar cells was determined to be a key factor in observed arcing rates. These rates could be reduced by greater than a factor of 100 by eliminating or fully outgassing the excess adhesive remaining at the edge of the solar cells. Optical emission from solar cell arcs was observed to correlate linearly with arc current, both temporally and in total intensity. Solar cell arcing rates were also observed to scale linearly with plasma density. The plasma scaling is in good agreement with a theory based on enhanced field electron emission charging of dielectric surfaces, leading to enhanced electric fields at the conductor/adhesive/plasma triple junction. Apparent thresholds for solar cell arcing are reported.

  6. Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1.

    PubMed

    Castilla, Carolina; Flores, M Luz; Medina, Rafael; Pérez-Valderrama, Begoña; Romero, Francisco; Tortolero, María; Japón, Miguel A; Sáez, Carmen

    2014-10-01

    PTTG1 protein, the human securin, has a central role in sister chromatid separation during mitosis, and its altered expression has been reported in many tumor types. Paclitaxel is a widely used chemotherapeutic drug, whose mechanism of action is related to its ability to arrest cells in mitosis and the subsequent induction of the intrinsic apoptotic pathway. By using two prostate cancer cell lines with different responses to paclitaxel treatment, we have identified two situations in which PTTG1 influences cell fate differentially. In slippage-prone PC3 cells, both PTTG1 downregulation and overexpression induce an increase in mitotic cells that is associated with diminished apoptosis after paclitaxel treatment. In LNCaP cells, however, PTTG1 downregulation prevents mitotic entry and, subsequently, inhibits mitosis-associated, paclitaxel-induced apoptosis. In contrast, PTTG1 overexpression induces an increase in mitotic cells and apoptosis after paclitaxel treatment. We have also identified a role for Mcl-1 protein in preventing apoptosis during mitosis in PC3 cells, as simultaneous PTTG1 and Mcl-1 silencing enhances mitosis-associated apoptosis after paclitaxel treatment. The finding that a more efficient mitotic arrest alone in PC3 cells is not enough to increase apoptosis was also confirmed with the observation that a selected paclitaxel-resistant PC3 cell line showed an apoptosis-resistant phenotype associated with increased mitosis upon paclitaxel treatment. These findings could contribute to identify putative responsive and nonresponsive cells and help us to approach incomplete responses to paclitaxel in the clinical setting. PMID:25122070

  7. Plasma-activated medium induced apoptosis on tumor cells

    NASA Astrophysics Data System (ADS)

    Hori, Masaru; Tanaka, Hiromasa; Mizuno, Masaaki; Nakamura, Kae; Kajiyama, Hiroaki; Takeda, Keigo; Ishikawa, Kenji; Kano, Hiroyuki; Kikkawa, Fumitaka

    2013-09-01

    The non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. In this study, the fresh medium was treated with our developed NEAPP, ultra-high electron density (approximately 2 × 1016 cm-3). The medium called the plasma-activated medium (PAM) killed not normal cells but tumor cells through induction of apoptosis. Cell proliferation assays showed that the tumor cells were selectively killed by the PAM. Those cells induced apoptosis using an apoptotic molecular marker, cleaved Caspase3/7. The molecular mechanisms of PAM-mediated apoptosis in the tumor cells were also found that the PAM downregulated the expression of AKT kinase, a marker molecule in a survival signal transduction pathway. These results suggest that PAM may be a promising tool for tumor therapy by downregulating the survival signals in cancers.

  8. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    PubMed Central

    Berquist, Sean W.; Hassan, Abd-elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H.

    2016-01-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  9. Collision Tumor With Renal Cell Carcinoma and Plasmacytoma: Further Evidence of a Renal Cell and Plasma Cell Neoplasm Relationship?

    PubMed

    Berquist, Sean W; Hassan, Abd-Elrahman Said; Miakicheva, Olga; Dufour, Catherine; Hamilton, Zachary; Shabaik, Ahmed; Derweesh, Ithaar H

    2016-05-01

    Renal solitary extramedullary plasmacytomas belong to a group of plasma cell neoplasms, which generally have been associated with renal cell carcinoma. We present a case report of a patient with collision tumor histology of extramedullary plasmacytoma and clear cell renal cell carcinoma, the first in the known literature. Standard work-up for a plasma cell neoplasm was conducted and the mass was resected. The patient remains disease-free at 28 months post-surgery. The report calls into question pre-surgical renal mass biopsy protocol and suggests a relationship between renal cell carcinoma and plasma cell neoplasms. PMID:27175345

  10. Analysis of non-thermal plasma-induced cell injury in human lung cancer cell lines

    NASA Astrophysics Data System (ADS)

    Kurita, Hirofumi; Sano, Kaori; Wada, Motoi; Mizuno, Kazue; Ono, Ryo; Yasuda, Hachiro; Takashima, Kazunori; Mizuno, Akira

    2015-09-01

    Recent progress of biomedical application of atmospheric pressure plasma shows that the biological effects are mainly due to reactive oxygen and nitrogen species (RONS) in liquid produced by the plasma exposure. To elucidate the cellular responses induced by exposure to the plasma, we focused on identification and quantification of reactive chemical species in plasma-exposed cell culture medium, and cell injury in mammalian cells after treatment of the plasma-exposed medium. In this study, we examined human lung cancer cell lines. The contribution of H2O2 to the cellular responses was considered. Here, an atmospheric pressure plasma jet (APPJ) sustained by a pulsed power supply in argon was used. After APPJ exposure to cell culture medium, RONS detection in liquid was conducted. It showed that OH radical, ONOO-, NO2-, NO3-, and H2O2 were produced in the plasma-exposed medium. Cellular responses of human lung cancer cell lines to the plasma-exposed medium in a concentration-dependence manner were also studied. It showed that the plasma-exposed medium and the H2O2 treatment gave similar reduction in viability and induction of apoptosis. This work was partly supported by MEXT KAKENHI Grant Number 24108005 and JSPS KAKENHI Grant Number 26390096.

  11. Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities.

    PubMed

    Bernaudin, Françoise; Verlhac, Suzanne; Arnaud, Cécile; Kamdem, Annie; Hau, Isabelle; Leveillé, Emmanuella; Vasile, Manuela; Kasbi, Florence; Madhi, Fouad; Fourmaux, Christine; Biscardi, Sandra; Gluckman, Eliane; Socié, Gérard; Dalle, Jean-Hugues; Epaud, Ralph; Pondarré, Corinne

    2016-04-01

    Stroke risk in sickle cell anemia (SCA), predicted by high transcranial Doppler (TCD) velocities, is prevented by transfusions. We present the long-term follow-up of SCA children from the Créteil newborn cohort (1992-2012) detected at risk by TCD and placed on chronic transfusions. Patients with normalized velocities and no stenosis were treated with hydroxyurea, known to decrease anemia and hemolytic rate. Trimestrial Doppler was performed and transfusions restarted immediately in the case of reversion to abnormal velocities. Patients with a genoidentical donor underwent transplant. Abnormal time-averaged maximum mean velocities (TAMMV) ≥200 cm/s were detected in 92 SCA children at a mean age of 3.7 years (range, 1.3-8.3 years). No stroke occurred posttransfusion after a mean follow-up of 6.1 years. Normalization of velocities (TAMMV < 170 cm/s) was observed in 83.5% of patients. Stenosis, present in 27.5% of patients, was associated with the risk of non-normalization (P< .001). Switch from transfusions to hydroxyurea was prescribed for 45 patients, with a mean follow-up of 3.4 years. Reversion, predicted by baseline reticulocyte count ≥400 × 10(9)/L (P< .001), occurred in 28.9% (13/45) patients at the mean age of 7.1 years (range, 4.3-9.5 years). Transplant, performed in 24 patients, allowed transfusions to be safely stopped in all patients and velocities to be normalized in 4 patients who still had abnormal velocities on transfusions. This long-term cohort study shows that transfusions can be stopped not only in transplanted patients but also in a subset of patients switched to hydroxyurea, provided trimestrial Doppler follow-up and immediate restart of transfusions in the case of reversion. PMID:26851292

  12. Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

    PubMed

    Abrass, C K; Berfield, A K; Ryan, M C; Carter, W G; Hansen, K M

    2006-09-01

    Mice with targeted disruption of the lama3 gene, which encodes the alpha3 chain of laminin-5 (alpha3beta3gamma2, 332), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans. These animals also develop abnormalities in glomerulogenesis. In both wild-type and mutant animals (lama3(-/-)), podocytes secrete glomerular basement membrane and develop foot processes. Endothelial cells migrate into this scaffolding and secrete a layer of basement membrane that fuses with the one formed by the podocyte. In lama3(-/-) animals, glomerular maturation arrests at this stage. Endothelial cells do not attenuate, develop fenestrae, or form typical lumens, and mesangial cells (MCs) were not identified. LN alpha3 subunit (LAMA3) protein was identified in the basement membrane adjacent to glomerular endothelial cells (GEnCs) in normal rats and mice. In developing rat glomeruli, the LAMA3 subunit was first detectable in the early capillary loop stage, which corresponds to the stage at which maturation arrest was observed in the mutant mice. Lama3 mRNA and protein were identified in isolated rat and mouse glomeruli and cultured rat GEnCs, but not MC. These data document expression of LAMA3 in glomeruli and support a critical role for it in GEnC differentiation. Furthermore, LAMA3 chain expression and/or another product of endothelial cells are required for MC migration into the developing glomerulus. PMID:16850021

  13. Role of dendritic cell-mediated abnormal immune response in visceral hypersensitivity

    PubMed Central

    Li, Meng; Zhang, Lu; Lu, Bin; Chen, Zhe; Chu, Li; Meng, Lina; Fan, Yihong

    2015-01-01

    The role of dendritic cells (DCs) in irritable bowel syndrome (IBS) is unclear. This study tested the hypothesis that intestinal DCs induced visceral hypersensitivity in IBS rats through mast cell (MC) activation. The IBS rat model was established by combining colorectal distension with restraint stress. The number of CD103-positive cells in colon was higher in the IBS group. Expression of PAR-2, IL-4 and IL-9 in the colonic mucosa was higher in the IBS group. Mesenteric lymph node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated and purified by a magnetic labeling-based technique; they were cultured alone or co-cultured (T4+DC/T8+DC). The coculture of MLNDCs and CD4+ T cells had the highest IL-4 secretion in the IBS group, while IL-9 expression was higher in the cultures containing CD8+ T cells. Our findings indicate that an increased number of DCs in the colon stimulated CD4+ T cells to secrete high levels of IL-4, which led to the activation of MCs and subsequently resulted in visceral hypersensitivity. PMID:26550249

  14. Abnormal centrosomal structure and duplication in Cep135-deficient vertebrate cells

    PubMed Central

    Inanç, Burcu; Pütz, Monika; Lalor, Pierce; Dockery, Peter; Kuriyama, Ryoko; Gergely, Fanni; Morrison, Ciaran G.

    2013-01-01

    Centrosomes are key microtubule-organizing centers that contain a pair of centrioles, conserved cylindrical, microtubule-based structures. Centrosome duplication occurs once per cell cycle and relies on templated centriole assembly. In many animal cells this process starts with the formation of a radially symmetrical cartwheel structure. The centrosomal protein Cep135 localizes to this cartwheel, but its role in vertebrates is not well understood. Here we examine the involvement of Cep135 in centriole function by disrupting the Cep135 gene in the DT40 chicken B-cell line. DT40 cells that lack Cep135 are viable and show no major defects in centrosome composition or function, although we note a small decrease in centriole numbers and a concomitant increase in the frequency of monopolar spindles. Furthermore, electron microscopy reveals an atypical structure in the lumen of Cep135-deficient centrioles. Centrosome amplification after hydroxyurea treatment increases significantly in Cep135-deficient cells, suggesting an inhibitory role for the protein in centrosome reduplication during S-phase delay. We propose that Cep135 is required for the structural integrity of centrioles in proliferating vertebrate cells, a role that also limits centrosome amplification in S-phase–arrested cells. PMID:23864714

  15. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis.

    PubMed

    van Wijk, Richard; van Solinge, Wouter W

    2005-12-15

    The red blood cell depends solely on the anaerobic conversion of glucose by the Embden-Meyerhof pathway for the generation and storage of high-energy phosphates, which is necessary for the maintenance of a number of vital functions. Many red blood cell enzymopathies have been described that disturb the erythrocyte's integrity, shorten its cellular survival, and result in hemolytic anemia. By far the majority of these enzymopathies are hereditary in nature. In this review, we summarize the current knowledge regarding the genetic, biochemical, and structural features of clinically relevant red blood cell enzymopathies involved in the Embden-Meyerhof pathway and the Rapoport-Luebering shunt. PMID:16051738

  16. T-cell abnormalities after mediastinal irradiation for lung cancer. The in vitro influence of synthetic thymosin alpha-1

    SciTech Connect

    Schulof, R.S.; Chorba, T.L.; Cleary, P.A.; Palaszynski, S.R.; Alabaster, O.; Goldstein, A.L.

    1985-03-01

    The effects of mediastinal irradiation (RT) on the numbers and functions of purified peripheral blood T-lymphocytes from patients with locally advanced non-small cell lung cancer were evaluated. The patients were candidates for a randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha-1. Twenty-one patients studied before RT did not exhibit any significant difference in T-cell numbers or function compared to age-matched healthy subjects. However, 41 patients studied within 1 week after completing RT exhibited significant depressions of E-rosette-forming cells at 4 degrees C (E4 degrees-RFC)/mm3, E-rosette-forming cells at 29 degrees C (E29 degrees-RFC)/mm3, OKT3/mm3, OKT4/mm3, and OKT8/mm3 (P . 0.0001); total T-cell percentages (%OKT3, P . 0.01); and T-cell proliferative responses in mixed lymphocyte cultures (MLR) (P . 0.01) and to the mitogen phytohemagglutinin under suboptimal conditions (P less than or equal to 0.03). Nine patients studied before and after RT showed a significant increase in OKT4/OKT8 (P . 0.01) following RT. A short-term in vitro incubation with thymosin alpha-1 could enhance MLR of T-cells in 12 of 27 patients with post-RT abnormalities. In 13 patients who were treated with placebo, the RT-induced depression of T-cell numbers and function persisted for at least 3 to 4 months. In addition, in 12 patients progressive decreases developed in %E4 degrees-RFC, %OKT3, %OKT4, and OKT4/OKT8, which always preceded clinical relapse.

  17. Spatial Intensity Distribution Analysis Reveals Abnormal Oligomerization of Proteins in Single Cells.

    PubMed

    Godin, Antoine G; Rappaz, Benjamin; Potvin-Trottier, Laurent; Kennedy, Timothy E; De Koninck, Yves; Wiseman, Paul W

    2015-08-18

    Knowledge of membrane receptor organization is essential for understanding the initial steps in cell signaling and trafficking mechanisms, but quantitative analysis of receptor interactions at the single-cell level and in different cellular compartments has remained highly challenging. To achieve this, we apply a quantitative image analysis technique-spatial intensity distribution analysis (SpIDA)-that can measure fluorescent particle concentrations and oligomerization states within different subcellular compartments in live cells. An important technical challenge faced by fluorescence microscopy-based measurement of oligomerization is the fidelity of receptor labeling. In practice, imperfect labeling biases the distribution of oligomeric states measured within an aggregated system. We extend SpIDA to enable analysis of high-order oligomers from fluorescence microscopy images, by including a probability weighted correction algorithm for nonemitting labels. We demonstrated that this fraction of nonemitting probes could be estimated in single cells using SpIDA measurements on model systems with known oligomerization state. Previously, this artifact was measured using single-step photobleaching. This approach was validated using computer-simulated data and the imperfect labeling was quantified in cells with ion channels of known oligomer subunit count. It was then applied to quantify the oligomerization states in different cell compartments of the proteolipid protein (PLP) expressed in COS-7 cells. Expression of a mutant PLP linked to impaired trafficking resulted in the detection of PLP tetramers that persist in the endoplasmic reticulum, while no difference was measured at the membrane between the distributions of wild-type and mutated PLPs. Our results demonstrate that SpIDA allows measurement of protein oligomerization in different compartments of intact cells, even when fractional mislabeling occurs as well as photobleaching during the imaging process, and

  18. Osteoclast cytomorphometry demonstrates an abnormal population in B cell malignancies but not in multiple myeloma.

    PubMed

    Chappard, D; Rossi, J F; Bataille, R; Alexandre, C

    1991-01-01

    Increased bone resorption in the vicinity of myeloma cells is mediated by local stimulating factors. Other malignancies of the B cell lineage are also able to produce resorbing factors responsible for increased bone resorption. We have studied three groups of subjects: 10 patients with overt multiple myeloma, 10 patients with a B cell malignancy, and 10 healthy human subjects as controls. Patients were studied at the time of diagnosis and had a transiliac bone biopsy. Osteoclasts were evident on histological sections by their acid phosphatase activity. A software was developed on an automatic image analyzer (Leitz TAS+) for measuring the maximal Feret's diameter (Oc.Le) of each osteoclast (corresponding to the osteoclast length). The histogram of Oc.Le frequency distribution was supplied in each group. In myeloma patients, the Oc.Le frequency distribution was similar to that in normal subjects and showed the histogram to be asymetric with a positive skew (maximum peak at 20-25 microns). With a graphical analysis, this distribution was shown to follow a lognormal distribution corresponding to a homogeneous osteoclast population. In other B cell malignancies, Oc.Le displayed a bimodal distribution with a peak at 20-25 microns and a lower peak at 10-15 microns. The graphical analysis showed that small (mononucleated?) osteoclasts are present in B cell malignancies with normal osteoclasts. This might reflect the secretion of different soluble factors by malignant cells of the B lymphocyte lineage. PMID:1706639

  19. GLYCEMIC REGULATION AND INSULIN SECRETION ARE ABNORMAL IN CYSTIC FIBROSIS PIGS DESPITE SPARING OF ISLET CELL MASS

    PubMed Central

    Uc, Aliye; Olivier, Alicia K.; Griffin, Michelle A.; Meyerholz, David K.; Yao, Jianrong; Abu-El-Haija, Maisam; Buchanan, Katherine M.; Vanegas Calderón, Oriana G.; Abu-El-Haija, Marwa; Pezzulo, Alejandro A.; Reznikov, Leah R.; Hoegger, Mark J.; Rector, Michael V.; Ostedgaard, Lynda S.; Taft, Peter J.; Gansemer, Nick D.; Ludwig, Paula S.; Hornick, Emma E.; Stoltz, David A.; Ode, Katie L.; Welsh, Michael J.; Engelhardt, John F.; Norris, Andrew W.

    2015-01-01

    Diabetes is a common and significant comorbidity in cystic fibrosis (CF). The pathogenesis of CF-related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared to non-CF. In summary, glycemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD. PMID:25142104

  20. Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells

    PubMed Central

    Nguyen, Ngoc Hoan; Park, Hyung Jun; Yang, Sang Sik; Choi, Kyeong Sook; Lee, Jong-Soo

    2016-01-01

    The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity. PMID:27364630

  1. Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells.

    PubMed

    Nguyen, Ngoc Hoan; Park, Hyung Jun; Yang, Sang Sik; Choi, Kyeong Sook; Lee, Jong-Soo

    2016-01-01

    The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity. PMID:27364630

  2. Detection of numerical chromosomal abnormalities (chr. 1 and 18) before and after photodynamic therapy of human bladder carcinoma cells in vitro

    NASA Astrophysics Data System (ADS)

    Bachor, Ruediger; Reich, Ella D.; Kleinschmidt, Klaus; Hautmann, Richard E.

    1997-12-01

    The application of nonradioactive in situ hybridization with chromosome-specific probes for cytogenetic analysis has increased significantly in recent years. In the field of photodynamic therapy (PDT) the hypothesis is that after PDT the remaining viable malignant cells are potentially metastatic cells. Therefore, we performed in vitro experiments on human bladder carcinoma cells to evaluate numerical chromosomal abnormalities before and after PDT. The possible genotoxic effect of PDT with porphycene (AamTPPn) appears to be small based on criteria such as numerical chromosomal abnormalities for chromosome 1 and 18.

  3. Systemic mastocytosis with plasma cell dyscrasia: report of a case.

    PubMed

    Pullarkat, Sheeja T; Sedarat, Franklin; Paquette, Ronald; Said, Jonathan

    2008-07-01

    Systemic mastocytosis (SM) comprises a heterogeneous group of disorders characterized by infiltration of bone marrow and other tissues by neoplastic mast cells. A subset of patients with SM has associated hematologic malignancy usually of myeloid origin and comprises an entity termed systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) by the current WHO classification. Reports of clonal lymphoid malignancies associated with SM are rare. We describe a patient who was simultaneously diagnosed with indolent SM and a plasma cell dyscrasia fitting the definition of monoclonal gammopathy of undetermined significance (MGUS). We also discuss the pathologic interaction between the neoplastic mast cells of SM and the lymphoid/plasma cell malignancy when these two entities coexist. PMID:18061667

  4. MicroRNA-122 Influences the Development of Sperm Abnormalities from Human Induced Pluripotent Stem Cells by Regulating TNP2 Expression

    PubMed Central

    Huang, Yongyi; Liu, Jianjun; Zhao, Yanhui; Jiang, Lizhen; Huang, Qin

    2013-01-01

    Sperm abnormalities are one of the main factors responsible for male infertility; however, their pathogenesis remains unclear. The role of microRNAs in the development of sperm abnormalities in infertile men has not yet been investigated. Here, we used human induced pluripotent stem cells to investigate the influence of miR-122 expression on the differentiation of these cells into spermatozoa-like cells in vitro. After induction, mutant miR-122-transfected cells formed spermatozoa-like cells. Flow cytometry of DNA content revealed a significant increase in the haploid cell population in spermatozoa-like cells derived from mutant miR-122-transfected cells as compared to those derived from miR-122-transfected cells. During induction, TNP2 and protamine mRNA and protein levels were significantly higher in mutant miR-122-transfected cells than in miR-122-transfected cells. High-throughput isobaric tags for relative and absolute quantification were used to identify and quantify the different protein expression levels in miR-122- and mutant miR-122-transfected cells. Among all the proteins analyzed, the expression of lipoproteins, for example, APOB and APOA1, showed the most significant difference between the two groups. This study illustrates that miR-122 expression is associated with abnormal sperm development. MiR-122 may influence spermatozoa-like cells by suppressing TNP2 expression and inhibiting the expression of proteins associated with sperm development. PMID:23327642

  5. Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome

    PubMed Central

    Brown, Audrey E.; Jones, David E.; Walker, Mark; Newton, Julia L.

    2015-01-01

    Background Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects. Methods Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise. Results In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured. Conclusion EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets. PMID:25836975

  6. Abnormal mitotic spindle assembly and cytokinesis induced by D-Limonene in cultured mammalian cells.

    PubMed

    Mauro, Maurizio; Catanzaro, Irene; Naselli, Flores; Sciandrello, Giulia; Caradonna, Fabio

    2013-11-01

    D-Limonene is found widely in citrus and many other plant species; it is a major constituent of many essential oils and is used as a solvent for commercial purposes. With the discovery of its chemotherapeutic properties against cancer, it is important to investigate the biological effects of the exposure to D-Limonene and elucidate its, as yet unknown, mechanism of action. We reported here that D-Limonene is toxic in V79 Chinese hamster cells in a dose-dependent manner. Moreover, to determine the cellular target of D-Limonene, we performed morphological observations and immunocytochemical analysis and we showed that this drug has a direct effect on dividing cells preventing assembly of mitotic spindle microtubules. This affects both chromosome segregation and cytokinesis, resulting in aneuploidy that in turn can lead to cell death or genomic instability. PMID:23913329

  7. Enhancement of red blood cell aggregation by plasma triglycerides.

    PubMed

    Cicha, I; Suzuki, Y; Tateishi, N; Maeda, N

    2001-01-01

    The effects of plasma triglycerides level on human red blood cells (RBCs) indices, hematological parameters, RBCs aggregation velocity and whole blood viscosity were studied at 2 hours after high-fat or low-fat meal. Proteins, triglycerides and cholesterol levels of plasma were analysed. The RBCs rouleaux formation rate was measured in 70% autologous plasma (with 30% phosphate-buffered saline, PBS) or 1 g/dl dextran T70 solution (with 4 g/dl bovine serum albumin) in PBS, using a low-shear rheoscope. The results were grouped according to triglycerides content in plasma. No significant difference in whole blood viscosity, hematological parameters, RBC indices, protein and cholesterol content was observed between high-fat and low-fat blood samples. There was a significant increase in rouleaux formation rate of samples with high triglyceride levels, when measured in 70% autologous plasma, but it was not significant in dextran T70 containing medium. In conclusion, the results obtained suggest that alteration of plasma lipid levels as well as possible changes in the cell membrane lipid composition lead to enhanced RBC aggregation. PMID:11564913

  8. Plasma Treatment of Single-Cell Niobium SRF Cavities

    SciTech Connect

    J. Upadhyay, M. Nikolić, S. Popović, L. Vušković, H.L. Phillips, A-M. Valente-Feliciano

    2011-03-01

    Superconducting radio frequency cavities of bulk Niobium are integral components of particle accelerators based on superconducting technology. Wet chemical processing is the commonly used procedure for impurities and surface defects removal and surface roughness improvement , both required to improve the RF performance of the cavity. We are studying plasma etching as an alternate technique to process these cavities. The uniformity of the plasma sheath at the inner wall of the cavity is one prerequisite for its uniform etching. We are developing electro-optic diagnostic techniques to assess the plasma uniformity. Multiple electro-optical probes are placed at different locations of the single cell cavity to diagnose the electrical and optical properties of the plasma. The electrical parameters are required to understand the kinetic nature of the plasma and the optical emission spectroscopy provides the spatial distribution of radicals in the plasma. The spatial variation of the plasma parameters inside the cavity and their effect on the etching of niobium samples placed at different locations in the cavity will be presented.

  9. Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways.

    PubMed

    Khan, S M; Cassarino, D S; Abramova, N N; Keeney, P M; Borland, M K; Trimmer, P A; Krebs, C T; Bennett, J C; Parks, J K; Swerdlow, R H; Parker, W D; Bennett, J P

    2000-08-01

    Alzheimer's disease (AD) is characterized by the deposition in brain of beta-amyloid (Abeta) peptides, elevated brain caspase-3, and systemic deficiency of cytochrome c oxidase. Although increased Abeta deposition can result from mutations in amyloid precursor protein or presenilin genes, the cause of increased Abeta deposition in sporadic AD is unknown. Cytoplasmic hybrid ("cybrid") cells made from mitochondrial DNA of nonfamilial AD subjects show antioxidant-reversible lowering of mitochondrial membrane potential (delta(gYm), secrete twice as much Abeta(1-40) and Abeta(1-42), have increased intracellular Abeta(1-40) (1.7-fold), and develop Congo red-positive Abeta deposits. Also elevated are cytoplasmic cytochrome c (threefold) and caspase-3 activity (twofold). Increased AD cybrid Abeta(1-40) secretion was normalized by inhibition of caspase-3 or secretase and reduced by treatment with the antioxidant S(-)pramipexole. Expression of AD mitochondrial genes in cybrid cells depresses cytochrome c oxidase activity and increases oxidative stress, which, in turn, lowers delta(psi)m. Under stress, cells with AD mitochondrial genes are more likely to activate cell death pathways, which drive caspase 3-mediated Abeta peptide secretion and may account for increased Abeta deposition in the AD brain. Therapeutic strategies for reducing neurodegeneration in sporadic AD can address restoration of delta(psi)m and reduction of elevated Abeta secretion. PMID:10939564

  10. Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer

    PubMed Central

    Shao, Weiwei; Wang, Quhui; Wang, Feiran; Jiang, Yasu; Xu, Meirong; Xu, Junfei

    2016-01-01

    The aim of this study was to investigate the calcyphosine (CAPS) expression in human colorectal cancer (CRC) and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004), invasive depth (P<0.001), lymph node metastasis (P=0.003), tumor node metastasis stage (P=0.017), and distant metastasis (P=0.042). Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan–Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients. PMID:26889086

  11. The Effect of Prolonged Culture of Chromosomally Abnormal Human Embryos on The Rate of Diploid Cells

    PubMed Central

    Bazrgar, Masood; Gourabi, Hamid; Eftekhari-Yazdi, Poopak; Vazirinasab, Hamed; Fakhri, Mostafa; Hassani, Fatemeh; Chehrazi, Mohamad; Valojerdi, Mojtaba Rezazadeh

    2016-01-01

    Background A decrease in aneuploidy rate following a prolonged co-culture of human blastocysts has been reported. As co-culture is not routinely used in assisted reproductive technology, the present study aimed to evaluate the effect of the prolonged single culture on the rate of diploid cells in human embryos with aneuploidies. Materials and Methods In this cohort study, we used fluorescence in situ hybridi- zation (FISH) to reanalyze surplus blastocysts undergoing preimplantation genetic diagnosis (PGD) on day 3 postfertilization. They were randomly studied on days 6 or 7 following fertilization. Results Of the 30 analyzed blastocysts, mosaicism was observed in 26(86.6%), while 2(6.7%) were diploid, and 2(6.7%) were triploid. Of those with mosaicism, 23(88.5%) were determined to be diploid-aneuploid and 3(11.5%) were aneuploid mosaic. The total frequency of embryos with more than 50% diploid cells was 33.3% that was lower on day 7 in comparison with the related value on day 6 (P<0.05); however, there were no differences when the embryos were classified according to maternal age, blastocyst developmental stage, total cell number on day 3, and embryo quality. Conclusion Although mosaicism is frequently observed in blastocysts, the prolonged single culture of blastocysts does not seem to increase the rate of normal cells. PMID:26985346

  12. Abnormal expression of Tim-3 antigen on peripheral blood T cells is associated with progressive disease in osteosarcoma patients.

    PubMed

    Liu, Hongliang; Zhi, Liqiang; Duan, Ning; Su, Pengxiao

    2016-08-01

    T-cell immunoglobulin and mucin-domain-3-containing molecule 3 (TIM-3) plays a pivotal role in immune regulation and has been found in various tumors. However, the prevalence and distribution of Tim-3 in osteosarcoma (OS) is still unclear. The aim of this study was to investigate the prevalence and distribution of Tim-3 in OS. Tim-3 on peripheral T cells from 82 OS patients and 60 healthy controls were examined by flow cytometry. Plasma levels of IL-2, IFN-γ, and TNF-α were measured by ELSIA. Tim-3 on both CD4(+) T and CD8(+) T cells were significantly upregulated in OS patients compared with healthy controls, Tim-3(+) CD4(+) T, and Tim-3(+) CD8(+) T cells were both negatively associated with serum levels of IL-2 and IFN-γ and TNF-α. In addition, Tim-3 showed similar levels in patients with different tumor sites. Nevertheless, patients with advanced tumor stage, metastasis, and pathological tumor fracture displayed significantly higher Tim-3 on both CD4(+) T cells and CD8(+) T cells than those with early tumor stage, without metastasis and pathological tumor fracture. Moreover, high Tim-3 on peripheral CD4(+) T cells or CD8(+) T were significantly related to poor overall survival (P = 0.014, P = 0.035, respectively). In conclusion, Tim-3 may be a potential diagnostic and prognostic biomarker for OS progression. PMID:27516959

  13. Effectiveness of plasma treatment on pancreatic cancer cells

    PubMed Central

    HATTORI, NORIFUMI; YAMADA, SUGURU; TORII, KOJI; TAKEDA, SHIGEOMI; NAKAMURA, KAE; TANAKA, HIROMASA; KAJIYAMA, HIROAKI; KANDA, MITSURO; FUJII, TSUTOMU; NAKAYAMA, GORO; SUGIMOTO, HIROYUKI; KOIKE, MASAHIKO; NOMOTO, SHUJI; FUJIWARA, MICHITAKA; MIZUNO, MASAAKI; HORI, MASARU; KODERA, YASUHIRO

    2015-01-01

    Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28±22 vs. 89±38 (mm3 ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy. PMID:26351772

  14. Evolution of Abnormal Plasma Glucagon Responses to Mixed-Meal Feedings in Youth With Type 1 Diabetes During the First 2 Years After Diagnosis

    PubMed Central

    Sherr, Jennifer; Tsalikian, Eva; Fox, Larry; Buckingham, Bruce; Weinzimer, Stuart; Tamborlane, William V.; White, Neil H.; Arbelaez, Ana Maria; Kollman, Craig; Ruedy, Katrina J.; Cheng, Peiyao; Beck, Roy W.

    2014-01-01

    OBJECTIVE To examine the evolution of the dysregulated glucagon responses to mixed-meal tolerance tests (MMTTs) in youth with recent-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS MMTTs were performed in 25 youth (9–18 years of age) with 1.5–12 months disease duration (year 1); 22 subjects were restudied 1 year later (year 2). Twenty nondiabetic (ND) control children were also studied. RESULTS In T1D children, MMTT-stimulated increases in glucagon were significantly greater than that in ND children (median increments: year 1, 21 pg/mL [16–30]; year 2, 25 pg/mL [16–30]; ND, 9 pg/mL [5–16]; P = 0.001 and P < 0.001, respectively). CONCLUSIONS In comparison with ND control children, exaggerated plasma glucagon responses to mixed-meal feedings are observed in youth with T1D within the first 2 years of diagnosis. Further studies to determine whether suppression of these abnormal responses may help to improve glycemic control are warranted. PMID:24696460

  15. Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

    PubMed Central

    Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

    2012-01-01

    Background/Aim Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. Methods We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Results Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Conclusions Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit

  16. Targeting the cancer cell cycle by cold atmospheric plasma

    NASA Astrophysics Data System (ADS)

    Volotskova, O.; Hawley, T. S.; Stepp, M. A.; Keidar, M.

    2012-09-01

    Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

  17. Systematization of the Mechanism by Which Plasma Irradiation Causes Cell Growth and Tumor Cell Death

    NASA Astrophysics Data System (ADS)

    Shimizu, Nobuyuki

    2015-09-01

    New methods and technologies have improved minimally invasive surgical treatment and saved numerous patients. Recently, plasma irradiation has been demonstrated that might be useful in medical field and the plasma irradiation device is expected to become practically applicable. Mild plasma coagulator showed some advantages such as hemostasis and adhesion reduction in experimental animal model, but the mechanism of plasma irradiation remains unclear. Our study group aim to clarify the mechanism of plasma irradiation effects, mainly focusing on oxidative stress using cultured cell lines and small animal model. First, a study using cultured cell lines showed that the culture medium that was activated by plasma irradiation (we called this kind of medium as ``PAM'' -plasma activated medium-) induced tumor cell death. Although this effect was mainly found to be due to hydrogen peroxide, the remaining portion was considered as the specific effect of the plasma irradiation and we are now studying focusing on this effect. Second, we established a mouse intra-peritoneal adhesion model and checked biological reaction that occurred in the adhesion part. Histopathological study showed inflammatory cells infiltration into adhesion part and the expression of PTX3 that might involve tissue repair around adhesion part. We also confirmed that cytokines IL-6 and IL-10 might be useful as a marker of adhesion formation in this model. Applying ``PAM'' or mild plasma irradiation in this model, we examine the effects of plasma on inflamed cells. The samples in these experiments would be applied to targeted proteomics analysis, and we aim to demonstrate the systematization of the cell's reaction by plasma irradiation.

  18. Silicon homojunction solar cells via a hydrogen plasma etching process

    NASA Astrophysics Data System (ADS)

    Xiao, S. Q.; Xu, S.; Zhou, H. P.; Wei, D. Y.; Huang, S. Y.; Xu, L. X.; Sern, C. C.; Guo, Y. N.; Khan, S.; Xu, Y.

    2013-03-01

    We report on the one-step formation of an efficient Si homojunction solar cell produced by a simple exposure of p-type Si wafers to low-temperature inductively coupled hydrogen plasma. The formation of oxygen thermal donors during hydrogen plasma treatment is responsible for the conductivity type conversion and the final formation of Si homojunction. The hydrogen plasma etching with suppressed heavy ion bombardment results in a relatively flat surface, which is favourable for deposition of passivation layers such as silicon nitride. The integrated Si homojunction solar cell consisting of Al/p-c-Si/n-c-Si/SiN/Al-grid has demonstrated a maximum photovoltaic conversion efficiency of 13.6%.

  19. P53 functional abnormality in mesenchymal stem cells promotes osteosarcoma development

    PubMed Central

    Velletri, T; Xie, N; Wang, Y; Huang, Y; Yang, Q; Chen, X; Chen, Q; Shou, P; Gan, Y; Cao, G; Melino, G; Shi, Y

    2016-01-01

    It has been shown that p53 has a critical role in the differentiation and functionality of various multipotent progenitor cells. P53 mutations can lead to genome instability and subsequent functional alterations and aberrant transformation of mesenchymal stem cells (MSCs). The significance of p53 in safeguarding our body from developing osteosarcoma (OS) is well recognized. During bone remodeling, p53 has a key role in negatively regulating key factors orchestrating the early stages of osteogenic differentiation of MSCs. Interestingly, changes in the p53 status can compromise bone homeostasis and affect the tumor microenvironment. This review aims to provide a unique opportunity to study the p53 function in MSCs and OS. In the context of loss of function of p53, we provide a model for two sources of OS: MSCs as progenitor cells of osteoblasts and bone tumor microenvironment components. Standing at the bone remodeling point of view, in this review we will first explain the determinant function of p53 in OS development. We will then summarize the role of p53 in monitoring MSC fidelity and in regulating MSC differentiation programs during osteogenesis. Finally, we will discuss the importance of loss of p53 function in tissue microenvironment. We expect that the information provided herein could lead to better understanding and treatment of OS. PMID:26775693

  20. Cytapheresis in the treatment of cell-affected blood disorders and abnormalities.

    PubMed

    Balint, Bela; Ostojic, Gordana; Pavlovic, Mirjana; Hrvacevic, Rajko; Pavlovic, Miodrag; Tukic, Ljiljana; Radovic, Milan

    2006-08-01

    This report presents our experience with cytaphereses performed in treatment of 476 patients. Leukapheresis was used in management of 68 patients with hyperleukocytosis leukostasis (WBC > or = 150 x 10(9)L(-1)). Average decrease in cell count after treatment was 73.3%. Plateletapheresis for 32 patients (platelets > or = 1500 x 10(9)L(-1)) was applied in order to prevent the thrombotic-hemorrhagic syndrome and resulted in a moderate platelet count reduction (84.3%). Erythrocytaphereses performed in treatment of 376 patients by manual or automated technique resulted in a rapid blood viscosity drop (42.4+/-7.1%). Patients with red blood cell exchanges (severe malaria and autoimmune hemolytic crisis) were in life-threatening situations and resulted in a prompt reduction of parasitized or antibody-coated RBCs and anemia correction. This study indicates that "conventional" TCs resulted in considerable cytoreduction only in patients with especially high cell count. This effect was not associated with bone marrow remission. The best clinical effect and long-term benefits were obtained using RBCX and antimalarial drugs in malaria patients who have had high-level parasitized-RBCs with multiorgan dysfunction. PMID:16935563

  1. Thermal Plasma Spraying Applied on Solid Oxide Fuel Cells

    NASA Astrophysics Data System (ADS)

    Soysal, D.; Arnold, J.; Szabo, P.; Henne, R.; Ansar, S. A.

    2013-06-01

    Solid oxide fuel cells (SOFCs), attractive for diverse applications in a broad range from small portable and auxiliary power units, up to central power systems, are conventionally produced by sintering methods. However, plasma spraying promises some advantages particularly for cells with metal support. In the present paper, research activities conducted in recent years at DLR as well as latest developments on plasma sprayed functional layers for SOFC as cathodes, electrolytes, and anodes are reported. Power densities of more than 800 mW/cm2 were achieved for plasma sprayed single cells of 12.56 cm2 size, and 300 mW/cm2, respectively, with a 250 W stack made of 10 cells. These values were attained at 0.7 V and 800 °C, with H2:N2 = 1:1 as fuel gas and air as oxidizing gas. Furthermore, continuous operation of more than 5000 h was attained with a plasma sprayed metal-supported SOFC stack which could also withstand more than 30 redox and thermal cycles.

  2. Potassium plasma cell facilitates thermionic energy conversion process

    NASA Technical Reports Server (NTRS)

    Richards, H. K.

    1967-01-01

    Thermionic energy converter converts nuclear generated heat directly into high frequency and direct current output. It consists of a potassium plasma cell, a tantalum emitter, and a silver plated copper collector. This conversion process eliminates the steam interface usually required between the atomic heat source and the electrical conversion system.

  3. Protein diffusion in plant cell plasma membranes: the cell-wall corral

    PubMed Central

    Martinière, Alexandre; Runions, John

    2013-01-01

    Studying protein diffusion informs us about how proteins interact with their environment. Work on protein diffusion over the last several decades has illustrated the complex nature of biological lipid bilayers. The plasma membrane contains an array of membrane-spanning proteins or proteins with peripheral membrane associations. Maintenance of plasma membrane microstructure can be via physical features that provide intrinsic ordering such as lipid microdomains, or from membrane-associated structures such as the cytoskeleton. Recent evidence indicates, that in the case of plant cells, the cell wall seems to be a major player in maintaining plasma membrane microstructure. This interconnection / interaction between cell-wall and plasma membrane proteins most likely plays an important role in signal transduction, cell growth, and cell physiological responses to the environment. PMID:24381579

  4. Shared clonal cytogenetic abnormalities in aberrant mast cells and leukemic myeloid blasts detected by single nucleotide polymorphism microarray-based whole-genome scanning.

    PubMed

    Frederiksen, John K; Shao, Lina; Bixby, Dale L; Ross, Charles W

    2016-04-01

    Systemic mastocytosis (SM) is characterized by a clonal proliferation of aberrant mast cells within extracutaneous sites. In a subset of SM cases, a second associated hematologic non-mast cell disease (AHNMD) is also present, usually of myeloid origin. Polymerase chain reaction and targeted fluorescence in situ hybridization studies have provided evidence that, in at least some cases, the aberrant mast cells are related clonally to the neoplastic cells of the AHNMD. In this work, a single nucleotide polymorphism microarray (SNP-A) was used to characterize the cytogenetics of the aberrant mast cells from a patient with acute myeloid leukemia and concomitant mast cell leukemia associated with a KIT D816A mutation. The results demonstrate the presence of shared cytogenetic abnormalities between the mast cells and myeloid blasts, as well as additional abnormalities within mast cells (copy-neutral loss of heterozygosity) not detectable by routine karyotypic analysis. To our knowledge, this work represents the first application of SNP-A whole-genome scanning to the detection of shared cytogenetic abnormalities between the two components of a case of SM-AHNMD. The findings provide additional evidence of a frequent clonal link between aberrant mast cells and cells of myeloid AHNMDs, and also highlight the importance of direct sequencing for identifying uncommon activating KIT mutations. PMID:26865278

  5. LOX-1 unlocks human plasma cell potential.

    PubMed

    Brink, Robert

    2014-10-16

    Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is best known for promoting atherosclerosis. In this issue of Immunity, Joo et al. (2014) find that dendritic cells triggered through LOX-1 can directly support plasmablast production via the production of the cytokines APRIL and BAFF. PMID:25367564

  6. Treatment of prostate cancer cell lines and primary cells using low temperature plasma

    NASA Astrophysics Data System (ADS)

    O'Connell, Deborah; Hirst, Adam; Frame, Fiona F.; Maitland, Norman J.

    2014-10-01

    The mechanisms of cell death after plasma treatment of both benign and cancerous prostate epithelial cells are investigated. Prostate cancer tissue was obtained with patient consent from targeted needle core biopsies following radical prostatectomy. Primary cells were cultured from cancer tissue and plated onto a chamber slide at a density of 10,000 cells per well in 200 microliter of stem cell media (SCM). The treated sample was previously identified as Gleason grade 7 cancer through tissue histo-pathology. A dielectric barrier discharge (DBD) jet configuration, with helium as a carrier gas, and 0.3% O2 admixture was used for treating the cells. Reactive oxygen and nitrogen species (RONS) produced by the plasma are believed to be the main mediators of the plasma-cell interaction and response. We found the concentration of reactive oxygen species (ROS) induced inside the cells increased with plasma exposure. Exposure to the plasma for >3 minutes showed high levels of DNA damage compared to untreated and hydrogen peroxide controls. Cell viability and cellular recovery are also investigated and will be presented. All findings were common to both cell lines, suggesting the potential of LTP therapy for both benign and malignant disease.

  7. Abnormalities in Cardiac Structure and Function in Adults with Sickle Cell Disease are not Associated with Pulmonary Hypertension

    PubMed Central

    Knight-Perry, Jessica E.; de las Fuentes, Lisa; Waggoner, Alan D.; Hoffmann, Raymond G.; Blinder, Morey A.; Dávila-Román, Victor G.; Field, Joshua J.

    2011-01-01

    Background In sickle cell disease (SCD), pulmonary hypertension (assessed by tricuspid regurgitant jet [TRJ] velocity ≥ 2.5 m/s) is associated with increased mortality. The relationships between TRJ velocity, left ventricular (LV) and right ventricular (RV) systolic and diastolic function (i.e., relaxation and compliance) have not been well characterized in SCD. Design and Methods Prospective study of 53 ambulatory SCD adults (age, mean: 34 years; range 21-65 years) and 33 African American controls to define the relationship between LV and RV function and TRJ velocity by use of echocardiography. Results SCD subjects had larger left and right atrial volumes and increased LV mass compared to controls. When SCD cases were compared to controls, LV and RV relaxation (i.e., E’) were similar. Among SCD subjects, pulmonary hypertension (TRJ ≥ 2.5 m/s) was present in 40% of cases. Higher TRJ velocity was correlated with larger LA volumes and areas in SCD cases. Additionally, some measures of LV (peak A, lateral and septal annulus E/E’) and RV compliance (TV E/E’) were correlated with TRJ velocity. No other measures of LV/RV systolic function or LV diastolic function (i.e., relaxation and compliance) were associated with TRJ velocity. Conclusions Ambulatory adults with SCD exhibited structural (i.e., LV and RV chamber enlargement) and functional (i.e., higher surrogate measures of LV and RV filling pressure) abnormalities compared to the control group. In SCD subjects, few abnormalities of LV and RV structure/function were associated with TRJ velocity. PMID:21873028

  8. Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass.

    PubMed

    Uc, Aliye; Olivier, Alicia K; Griffin, Michelle A; Meyerholz, David K; Yao, Jianrong; Abu-El-Haija, Maisam; Buchanan, Katherine M; Vanegas Calderón, Oriana G; Abu-El-Haija, Marwa; Pezzulo, Alejandro A; Reznikov, Leah R; Hoegger, Mark J; Rector, Michael V; Ostedgaard, Lynda S; Taft, Peter J; Gansemer, Nick D; Ludwig, Paula S; Hornick, Emma E; Stoltz, David A; Ode, Katie L; Welsh, Michael J; Engelhardt, John F; Norris, Andrew W

    2015-01-01

    Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD. PMID:25142104

  9. Trivalent dimethylarsenic compound induces histone H3 phosphorylation and abnormal localization of Aurora B kinase in HepG2 cells

    SciTech Connect

    Suzuki, Toshihide; Miyazaki, Koichi; Kita, Kayoko; Ochi, Takafumi

    2009-12-15

    Trivalent dimethylarsinous acid [DMA(III)] has been shown to induce mitotic abnormalities, such as centrosome abnormality, multipolar spindles, multipolar division, and aneuploidy, in several cell lines. In order to elucidate the mechanisms underlying these mitotic abnormalities, we investigated DMA(III)-mediated changes in histone H3 phosphorylation and localization of Aurora B kinase, which is a key molecule in cell mitosis. DMA(III) caused the phosphorylation of histone H3 (ser10) and was distributed predominantly in mitotic cells, especially in prometaphase cells. By contrast, most of the phospho-histone H3 was found to be localized in interphase cells after treatment with inorganic arsenite [iAs(III)], suggesting the involvement of a different pathway in phosphorylation. DMA(III) activated Aurora B kinase and slightly activated ERK MAP kinase. Phosphorylation of histone H3 by DMA(III) was effectively reduced by ZM447439 (Aurora kinase inhibitor) and slightly reduced by U0126 (MEK inhibitor). By contrast, iAs(III)-dependent histone H3 phosphorylation was markedly reduced by U0126. Aurora B kinase is generally localized in the midbody during telophase and plays an important role in cytokinesis. However, in some cells treated with DMA(III), Aurora B was not localized in the midbody of telophase cells. These findings suggested that DMA(III) induced a spindle abnormality, thereby activating the spindle assembly checkpoint (SAC) through the Aurora B kinase pathway. In addition, cytokinesis was not completed because of the abnormal localization of Aurora B kinase by DMA(III), thereby resulting in the generation of multinucleated cells. These results provide insight into the mechanism of arsenic tumorigenesis.

  10. Plasma Texturing of Silicon Solar Cells

    SciTech Connect

    Narayanan, Mohan; Roy, Madhu; Ruby, Douglas S.; Zaidi, Saleem H.

    1999-07-20

    Surface texture promotes enhanced light absorption in Si solar cells. The quality of lower cost multicrystalline-silicon (mc-Si) has increased to the point that its cell performance is close to that of single c-Si cells, with the major difference resulting from the inability to texture mc-Si affordably. This has reduced the cost-per-watt advantage of mc-Si. Surface texturing aimed at enhanced absorption in Si has been historically obtained by creating multimicrometer-sized pyramids using anisotropic wet etchants on single-crystalline silicon that take advantage of its single crystalline orientation. Since the surface feature sizes are several times the length of the incident solar wavelengths involved, the optical analysis of the reflected and absorbed light can be understood using geometrical optics. Geometrical textures reduce reflection and improve absorption by double-bounce and oblique light coupling into the semiconductor. However, geometrical texturing suffers from several disadvantages that limit its effectiveness. Some of these are listed below: (a) Wet-chemical anisotropic etching used to form random pyramids on <100> crystal orientation is not effective in the texturing of low-cost multicrystalline wafers, (b) Anti-reflection films deposited on random features to reduce reflection have a resonant structure limiting their effectiveness to a narrow range of angles and wavelengths. Various forms of surface texturing have been applied to mc-Si in research, including laser-structuring, mechanical grinding, porous-Si etching, and photolithographically defined etching. However, these may be too costly to ever be used in large-scale production. A Japanese firm has reported the development of an RIE process using Cl{sub 2} gas, which textures multiple wafers per batch, making it attractive for mass-production [1]. Using this process, they have produced a 17.1% efficient 225-cm{sup 2} mc-Si cell, which is the highest efficiency mc-Si cell of its size ever reported

  11. Successful treatment of plasma cell cheilitis with topical tacrolimus: report of two cases.

    PubMed

    Hanami, Yuka; Motoki, Yoshikazu; Yamamoto, Toshiyuki

    2011-01-01

    Plasma cell cheilitis is an uncommon chronic inflammatory dermatitis that presents with flat to slightly elevated erosive erythematous plaques. It is histologically characterized by plasma cell infiltrates into the mucosa. Other than the lip, genital areas are often involved, which is called plasma cell balanitis or vulvitis. Plasma cell cheilitis is sometimes resistant to conventional topical corticosteroid therapy. Other choices include oral griseofulvin, topical cyclosporine, and intralesional corticosteroid injection, all of which occasionally fail to produce satisfactory results. Recent reports show that topical calcineurin inhibitors are effective for plasma cell cheilitis, balanitis, and vulvitis. However, there are so far only 2 reports of plasma cell cheilitis successfully treated with topical pimecrolimus and tacrolimus. We present herein two cases of plasma cell cheilitis, in which topical tacrolimus showed beneficial effects, suggesting that this immunomodulatory agent is a promising option for plasma cell cheilitis. PMID:21382289

  12. Measurement of plasma-generated RONS in the cancer cells exposed by atmospheric pressure helium plasma jet

    NASA Astrophysics Data System (ADS)

    Joh, Hea Min; Baek, Eun Jeong; Kim, Sun Ja; Chung, Tae Hun

    2015-09-01

    The plasma-induced reactive oxygen and nitrogen species (RONS) could result in cellular responses including DNA damages and apoptotic cell death. These chemical species, O, O2-,OH, NO, and NO2-,exhibit strong oxidative stress and/or trigger signaling pathways in biological cells. Each plasma-generated chemical species having biological implication should be identified and quantitatively measured. For quantitative measurement of RONS, this study is divided into three stages; plasma diagnostics, plasma-liquid interactions, plasma-liquid-cell interactions. First, the optical characteristics of the discharges were obtained by optical emission spectroscopy to identify various excited plasma species. And the characteristics of voltage-current waveforms, gas temperature, and plume length with varying control parameters were measured. Next, atmospheric pressure plasma jet was applied on the liquid. The estimated OH radical densities were obtained by ultraviolet absorption spectroscopy at the liquid surface. And NO2-is detected by Griess test and compared between the pure liquid and the cell-containing liquid. Finally, bio-assays were performed on plasma treated human lung cancer cells (A549). Intracellular ROS production was measured using DCF-DA. Among these RONS, productions of NO and OH within cells were measured by DAF-2DA and APF, respectively. The data are very suggestive that there is a strong correlation among the production of RONS in the plasmas, liquids, and cells.

  13. Automated identification of abnormal metaphase chromosome cells for the detection of chronic myeloid leukemia using microscopic images

    NASA Astrophysics Data System (ADS)

    Wang, Xingwei; Zheng, Bin; Li, Shibo; Mulvihill, John J.; Chen, Xiaodong; Liu, Hong

    2010-07-01

    Karyotyping is an important process to classify chromosomes into standard classes and the results are routinely used by the clinicians to diagnose cancers and genetic diseases. However, visual karyotyping using microscopic images is time-consuming and tedious, which reduces the diagnostic efficiency and accuracy. Although many efforts have been made to develop computerized schemes for automated karyotyping, no schemes can get be performed without substantial human intervention. Instead of developing a method to classify all chromosome classes, we develop an automatic scheme to detect abnormal metaphase cells by identifying a specific class of chromosomes (class 22) and prescreen for suspicious chronic myeloid leukemia (CML). The scheme includes three steps: (1) iteratively segment randomly distributed individual chromosomes, (2) process segmented chromosomes and compute image features to identify the candidates, and (3) apply an adaptive matching template to identify chromosomes of class 22. An image data set of 451 metaphase cells extracted from bone marrow specimens of 30 positive and 30 negative cases for CML is selected to test the scheme's performance. The overall case-based classification accuracy is 93.3% (100% sensitivity and 86.7% specificity). The results demonstrate the feasibility of applying an automated scheme to detect or prescreen the suspicious cancer cases.

  14. B cell hyperactivity and abnormalities in T cell markers and immunoregulatory function in a patient with nucleoside phosphorylase deficiency.

    PubMed Central

    Zabay, J M; De La Concha, E G; Ludeña, C; Lozano, C; Pascual-Salcedo, D; Bootello, A; Gonzalezporqué, P

    1982-01-01

    We describe a 2 year old girl with nucleoside phosphorylase (PNP) deficiency, who had low blood T cell numbers and T lymphocyte blastogenic response to mitogens, hypergammaglobulinaemia, high titres of antibodies to many common antigens, various autoantibodies, a monoclonal IgM-kappa protein, an increased frequency of mature Ig containing blood B cells and a high production of Ig in vitro in unstimulated cultures. E rosetting cells showed faint or no immunofluorescence staining with monoclonal antibodies directed against T cell membrane antigens. In vitro Ig production in response to pokeweed mitogen was defective, and no T cell helper or suppressor activity was observed. It is suggested that the immunoregulatory deficiency might have caused the B cell hyperactivity. PMID:6819909

  15. The Glycome of Normal and Malignant Plasma Cells

    PubMed Central

    Hose, Dirk; Andrulis, Mindaugas; Moreaux, Jèrôme; Hielscher, Thomas; Willhauck-Fleckenstein, Martina; Merling, Anette; Bertsch, Uta; Jauch, Anna; Goldschmidt, Hartmut; Klein, Bernard; Schwartz-Albiez, Reinhard

    2013-01-01

    The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma. PMID:24386263

  16. Adipocyte cell size enlargement involves plasma membrane area increase.

    PubMed

    Chowdhury, H H; Zorec, R

    2012-07-01

    The adipocyte enlargement is associated with an increase in the cytoplasmic lipid content, but how the plasma membrane area follows this increase is poorly understood. We monitored single-cell membrane surface area fluctuations, which mirror the dynamics of exocytosis and endocytosis. We employed the patch-clamp technique to measure membrane capacitance (C(m)), a parameter linearly related to the plasma membrane area. Specifically, we studied whether insulin affects membrane area dynamics in adipocytes. A five-minute cell exposure to insulin increased resting C(m) by 12 ± 4%; in controls the change in C(m) was not different from zero. We measured cell diameter of isolated rat adipocytes microscopically. Twenty-four hour exposure of cells to insulin resulted in a significant increase in cell diameter by 5.1 ± 0.6%. We conclude that insulin induces membrane area increase, which may in chronic hyperinsulinemia promote the enlargement of plasma membrane area, acting in concert with other insulin-mediated metabolic effects on adipocytes. PMID:22540353

  17. Functional Implications of Plasma Membrane Condensation for T Cell Activation

    PubMed Central

    Quinn, Carmel M.; Engelhardt, Karin; Williamson, David; Grewal, Thomas; Jessup, Wendy; Harder, Thomas; Gaus, Katharina

    2008-01-01

    The T lymphocyte plasma membrane condenses at the site of activation but the functional significance of this receptor-mediated membrane reorganization is not yet known. Here we demonstrate that membrane condensation at the T cell activation sites can be inhibited by incorporation of the oxysterol 7-ketocholesterol (7KC), which is known to prevent the formation of raft-like liquid-ordered domains in model membranes. We enriched T cells with 7KC, or cholesterol as control, to assess the importance of membrane condensation for T cell activation. Upon 7KC treatment, T cell antigen receptor (TCR) triggered calcium fluxes and early tyrosine phosphorylation events appear unaltered. However, signaling complexes form less efficiently on the cell surface, fewer phosphorylated signaling proteins are retained in the plasma membrane and actin restructuring at activation sites is impaired in 7KC-enriched cells resulting in compromised downstream activation responses. Our data emphasizes lipids as an important medium for the organization at T cell activation sites and strongly indicates that membrane condensation is an important element of the T cell activation process. PMID:18509459

  18. Cold Atmospheric Plasma for Selectively Ablating Metastatic Breast Cancer Cells

    PubMed Central

    Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

    2013-01-01

    Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atomospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy. PMID:24040051

  19. Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

    PubMed Central

    Sangkatumvong, S; Coates, T D; Khoo, M C K

    2010-01-01

    The objective of this study was to non-invasively assess cardiac autonomic control in subjects with sickle cell anemia (SCA) by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxic stimulus. Five African–American SCA patients and seven healthy control subjects were recruited to participate in this study. Each subject was exposed to a controlled hypoxic stimulus consisting of five breaths of nitrogen. Time-varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The confounding effects of changes in respiration on the HRV spectral indices were reduced by using a computational model. A significant decrease in the parameters related to parasympathetic control was detected in the post-hypoxic responses of the SCA subjects relative to normal controls. The spectral index related to sympathetic activity, on the other hand, showed a tendency to increase the following hypoxic stimulation, but the change was not significant. This study suggests that there is some degree of cardiovascular autonomic dysfunction in SCA that is revealed by the response to transient hypoxia. PMID:18460753

  20. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    PubMed

    Purrier, Nicole; Engeland, William C; Kofuji, Paulo

    2014-01-01

    Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

  1. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

    NASA Astrophysics Data System (ADS)

    Iseki, Sachiko; Nakamura, Kae; Hayashi, Moemi; Tanaka, Hiromasa; Kondo, Hiroki; Kajiyama, Hiroaki; Kano, Hiroyuki; Kikkawa, Fumitaka; Hori, Masaru

    2012-03-01

    Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

  2. Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma

    SciTech Connect

    Iseki, Sachiko; Tanaka, Hiromasa; Kondo, Hiroki; Hori, Masaru; Nakamura, Kae; Hayashi, Moemi; Kajiyama, Hiroaki; Kikkawa, Fumitaka; Kano, Hiroyuki

    2012-03-12

    Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.

  3. Plasma Electrode Pockels Cells for the Beamlet and NIF lasers

    SciTech Connect

    Rhodes, M.A.; Woods, B.; DeYoreo, J.; Atherton, J.

    1994-05-01

    We describe Plasma Electrode Pockels Cells (PEPC) for the Beamlet laser and the proposed National Ignition Facility (NIF) laser. These PEPCs, together with passive polarizers, function as large aperture (> 35 {times} 35 cm{sup 2}) optical switches enabling the design of high-energy (> 5 kJ), multipass laser amplifiers. In a PEPC, plasma discharges form on both sides of a thin (1 cm) electro-optic crystal (KDP). These plasma discharges produce highly conductive and transparent electrodes that facilitate rapid (< 100 ns) and uniform charging of the KDP up to the half-wave voltage (17 kV) and back to zero volts. We discuss the operating principles, design, and optical performance of the Beamlet PEPC and briefly discuss our plans to extend PEPC technology for the NIF.

  4. Plasma Electrode Pockels Cells for the Beamlet and NIF lasers

    SciTech Connect

    Rhodes, M.A.; Woods, B.; De Yoreo, J.; Atherton, J.

    1994-11-01

    The authors describe Plasma Electrode Pockels Cells (PEPC) for the Beamlet laser and the proposed National Ignition Facility (NIF) laser. These PEPCs, together with passive polarizers, function as large aperture (>35 x 35 cm{sup 2}) optical switches enabling the design of high-energy (>5 kJ), multipass laser amplifiers. In a PEPC, plasma discharges form on both sides of a thin (1 cm) electro-optic crystal (KDP). These plasma discharges produce highly conductive and transparent electrodes that facilitate rapid (<100 ns) and uniform charging of the KDP up to the half-wave voltage (17 kV) and back to zero volts. The authors discuss the operating principles, design, and optical performance of the Beamlet PEPC and briefly discuss their plans to extend PEPC technology for the NIF.

  5. Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch

    PubMed Central

    Muto, Akihiko; Ochiai, Kyoko; Kimura, Yoshitaka; Itoh-Nakadai, Ari; Calame, Kathryn L; Ikebe, Dai; Tashiro, Satoshi; Igarashi, Kazuhiko

    2010-01-01

    Two transcription factors, Pax5 and Blimp-1, form a gene regulatory network (GRN) with a double-negative loop, which defines either B-cell (Pax5 high) or plasma cell (Blimp-1 high) status as a binary switch. However, it is unclear how this B-cell GRN registers class switch DNA recombination (CSR), an event that takes place before the terminal differentiation to plasma cells. In the absence of Bach2 encoding a transcription factor required for CSR, mouse splenic B cells more frequently and rapidly expressed Blimp-1 and differentiated to IgM plasma cells as compared with wild-type cells. Genetic loss of Blimp-1 in Bach2−/− B cells was sufficient to restore CSR. These data with mathematical modelling of the GRN indicate that Bach2 achieves a time delay in Blimp-1 induction, which inhibits plasma cell differentiation and promotes CSR (Delay-Driven Diversity model for CSR). Reduction in mature B-cell numbers in Bach2−/− mice was not rescued by Blimp-1 ablation, indicating that Bach2 regulates B-cell differentiation and function through Blimp-1-dependent and -independent GRNs. PMID:20953163

  6. Particle-in-cell simulations of Hall plasma thrusters

    NASA Astrophysics Data System (ADS)

    Miranda, Rodrigo; Ferreira, Jose Leonardo; Martins, Alexandre

    2016-07-01

    Hall plasma thrusters can be modelled using particle-in-cell (PIC) simulations. In these simulations, the plasma is described by a set of equations which represent a coupled system of charged particles and electromagnetic fields. The fields are computed using a spatial grid (i.e., a discretization in space), whereas the particles can move continuously in space. Briefly, the particle and fields dynamics are computed as follows. First, forces due to electric and magnetic fields are employed to calculate the velocities and positions of particles. Next, the velocities and positions of particles are used to compute the charge and current densities at discrete positions in space. Finally, these densities are used to solve the electromagnetic field equations in the grid, which are interpolated at the position of the particles to obtain the acting forces, and restart this cycle. We will present numerical simulations using software for PIC simulations to study turbulence, wave and instabilities that arise in Hall plasma thrusters. We have sucessfully reproduced a numerical simulation of a SPT-100 Hall thruster using a two-dimensional (2D) model. In addition, we are developing a 2D model of a cylindrical Hall thruster. The results of these simulations will contribute to improve the performance of plasma thrusters to be used in Cubesats satellites currenty in development at the Plasma Laboratory at University of Brasília.

  7. Apoptosis in vascular cells induced by cold atmospheric plasma treatment

    NASA Astrophysics Data System (ADS)

    Sladek, Raymond; Stoffels, Eva

    2006-10-01

    Apoptosis is a natural mechanism of cellular self-destruction. It can be triggered by moderate, yet irreversible damage. Apoptosis plays a major role in tissue renewal. Artificial apoptosis induction will become a novel therapy that meets all requirements for tissue-saving surgery. Diseased tissues can disappear without inflammation and scarring. This is particularly important in treatment of blockages in body tracts (e.g. cardiovascular diseases). Artificial induction of apoptosis can be achieved by means of cold plasma treatment. In this work an atmospheric micro-plasma operated in helium/air has been used to induce apoptosis in vascular cells. Parametric studies of apoptosis induction have been conducted; the efficiency is almost 100%. The apoptotic factors are ROS/RNS (reactive oxygen and nitrogen species). Their densities in the plasma have been measured by mass spectrometry. For apoptosis induction, RNS seem to be more important than ROS, because of their relative abundance. Moreover, addition of a ROS scavenger (ascorbic acid) to the cell culture medium does not reduce the occurrence of apoptosis. Cold plasma is a very efficient tool for fundamental studies of apoptosis, and later, for controlled tissue removal in vivo.

  8. Influence of electron injection into 27 cm audio plasma cell on the plasma diagnostics

    SciTech Connect

    Haleem, N. A.; Ragheb, M. S.; Zakhary, S. G.; El Fiki, S. A.; Nouh, S. A.; El Disoki, T. M.

    2013-08-15

    In this article, the plasma is created in a Pyrex tube (L = 27 cm, φ= 4 cm) as a single cell, by a capacitive audio frequency (AF) discharge (f = 10–100 kHz), at a definite pressure of ∼0.2 Torr. A couple of tube linear and deviating arrangements show plasma characteristic conformity. The applied AF plasma and the injection of electrons into two gas mediums Ar and N{sub 2} revealed the increase of electron density at distinct tube regions by one order to attain 10{sup 13}/cm{sup 3}. The electrons temperature and density strengths are in contrast to each other. While their distributions differ along the plasma tube length, they show a decaying sinusoidal shape where their peaks position varies by the gas type. The electrons injection moderates electron temperature and expands their density. The later highest peak holds for the N{sub 2} gas, at electrons injection it changes to hold for the Ar. The sinusoidal decaying density behavior generates electric fields depending on the gas used and independent of tube geometry. The effect of the injected electrons performs a responsive impact on electrons density not attributed to the gas discharge. Analytical tools investigate the interaction of the plasma, the discharge current, and the gas used on the electrodes. It points to the emigration of atoms from each one but for greater majority they behave to a preferred direction. Meanwhile, only in the linear regime, small percentage of atoms still moves in reverse direction. Traces of gas atoms revealed on both electrodes due to sheath regions denote lack of their participation in the discharge current. In addition, atoms travel from one electrode to the other by overcoming the sheaths regions occurring transportation of particles agglomeration from one electrode to the other. The electrons injection has contributed to increase the plasma electron density peaks. These electrons populations have raised the generated electrostatic fields assisting the elemental ions

  9. Induction of Embryogenesis in Brassica Napus Microspores Produces a Callosic Subintinal Layer and Abnormal Cell Walls with Altered Levels of Callose and Cellulose

    PubMed Central

    Parra-Vega, Verónica; Corral-Martínez, Patricia; Rivas-Sendra, Alba; Seguí-Simarro, Jose M.

    2015-01-01

    The induction of microspore embryogenesis produces dramatic changes in different aspects of the cell physiology and structure. Changes at the cell wall level are among the most intriguing and poorly understood. In this work, we used high pressure freezing and freeze substitution, immunolocalization, confocal, and electron microscopy to analyze the structure and composition of the first cell walls formed during conventional Brassica napus microspore embryogenesis, and in cultures treated to alter the intracellular Ca2+ levels. Our results revealed that one of the first signs of embryogenic commitment is the formation of a callose-rich, cellulose-deficient layer beneath the intine (the subintinal layer), and of irregular, incomplete cell walls. In these events, Ca2+ may have a role. We propose that abnormal cell walls are due to a massive callose synthesis and deposition of excreted cytoplasmic material, and the parallel inhibition of cellulose synthesis. These features were absent in pollen-like structures and in microspore-derived embryos, few days after the end of the heat shock, where abnormal cell walls were no longer produced. Together, our results provide an explanation to a series of relevant aspects of microspore embryogenesis including the role of Ca2+ and the occurrence of abnormal cell walls. In addition, our discovery may be the explanation to why nuclear fusions take place during microspore embryogenesis. PMID:26635844

  10. [Multiple myeloma and other plasma cell dyscrasias].

    PubMed

    Nagy, Zsolt

    2016-06-01

    Multiple myeloma is the most common primary malignant disease of bone marrow. It mainly occurs among elderly people and, according to international databases, it is twice as frequent in men, however in our country this fact cannot be observed because of the high male mortality rate. The presence of this disease increased by more than one and the half times during the last 60 years. The five year survival for multiple myeloma has increased from 25% to 40% since the seventies due to high-dose chemotherapy followed by autologous stem cell transplantation and the new anti-myeloma drugs which were introduced in the last decade, such as immunomodulators (IMiD) like thalidomide, lenalidomide, pomalidomide and proteasome inhibitors (PI) like bortezomib, carfilzomib, ixazomib. The number of treatment options are growing fast, and not only because of using new combinations of medications, but also due to the development of investigational products which are available for the patients by participating in a clinical trial. PMID:27275642

  11. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    NASA Astrophysics Data System (ADS)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  12. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    NASA Astrophysics Data System (ADS)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-05-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  13. Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea.

    PubMed

    Jin, Yecheng; Ren, Naixia; Li, Shiwei; Fu, Xiaolong; Sun, Xiaoyang; Men, Yuqin; Xu, Zhigang; Zhang, Jian; Xie, Yue; Xia, Ming; Gao, Jiangang

    2016-01-01

    Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter's cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs. PMID:27255603

  14. Ectopic cerebellar cell migration causes maldevelopment of Purkinje cells and abnormal motor behaviour in Cxcr4 null mice.

    PubMed

    Huang, Guo-Jen; Edwards, Andrew; Tsai, Cheng-Yu; Lee, Yi-Shin; Peng, Lei; Era, Takumi; Hirabayashi, Yoshio; Tsai, Ching-Yen; Nishikawa, Shin-Ichi; Iwakura, Yoichiro; Chen, Shu-Jen; Flint, Jonathan

    2014-01-01

    SDF-1/CXCR4 signalling plays an important role in neuronal cell migration and brain development. However, the impact of CXCR4 deficiency in the postnatal mouse brain is still poorly understood. Here, we demonstrate the importance of CXCR4 on cerebellar development and motor behaviour by conditional inactivation of Cxcr4 in the central nervous system. We found CXCR4 plays a key role in cerebellar development. Its loss leads to defects in Purkinje cell dentritogenesis and axonal projection in vivo but not in cell culture. Transcriptome analysis revealed the most significantly affected pathways in the Cxcr4 deficient developing cerebellum are involved in extra cellular matrix receptor interactions and focal adhesion. Consistent with functional impairment of the cerebellum, Cxcr4 knockout mice have poor coordination and balance performance in skilled motor tests. Together, these results suggest ectopic the migration of granule cells impairs development of Purkinje cells, causes gross cerebellar anatomical disruption and leads to behavioural motor defects in Cxcr4 null mice. PMID:24516532

  15. Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea

    PubMed Central

    Jin, Yecheng; Ren, Naixia; Li, Shiwei; Fu, Xiaolong; Sun, Xiaoyang; Men, Yuqin; Xu, Zhigang; Zhang, Jian; Xie, Yue; Xia, Ming; Gao, Jiangang

    2016-01-01

    Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter’s cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs. PMID:27255603

  16. Relapsing intracranial plasma cell granuloma: A case report

    PubMed Central

    RENFROW, JACLYN J.; MITCHELL, JERRY W.; GOODMAN, MICHAEL; MELLEN, LEIGH A.; WILSON, JOHN A.; MOTT, RYAN T.; LESSER, GLENN J.

    2014-01-01

    Plasma cell granuloma is a pathological entity reported in nearly every organ system; however, intracranial cases remain rare. In the current case report, we present a case of intracranial plasma cell granuloma with the longest known follow-up period in the literature. Medical follow-up over 14 years, detailing four recurrences following the patient’s initial presentation and management, is presented. The patient’s treatment course consisted of three craniotomies, 3,600-cGy fractionated radiation and two courses of glucocorticoid therapy. In addition to disease surveillance using clinical examination and imaging, this case represents the first description of the clinical utility of analyzing changes in an inflammatory blood marker, the erythrocyte sedimentation rate, which coincided with recurrence and response to therapy. PMID:24396482

  17. Distinct mechanisms account for acquired von Willebrand syndrome in plasma cell dyscrasias.

    PubMed

    Dicke, Christina; Schneppenheim, Sonja; Holstein, Katharina; Spath, Brigitte; Bokemeyer, Carsten; Dittmer, Rita; Budde, Ulrich; Langer, Florian

    2016-05-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that may cause life-threatening hemorrhages in patients with plasma cell dyscrasias (PCDs). Early diagnosis and treatment require a thorough understanding of its underlying pathophysiology. Two patients with IgG MGUS presented with dramatically decreased plasma von Willebrand factor (VWF) and a severe type-1 pattern on multimer analysis. A prompt response to intravenous immunoglobulins (IVIG), but not to VWF/FVIII, was consistent with accelerated immunologic clearance of plasma VWF. Another IgG MGUS patient showed a type-2 pattern and a less pronounced response to IVIG, suggesting that additional mechanism(s) contributed to AVWS evolution. In a patient with Waldenström's macroglobulinemia and severe depletion of plasma VWF, multimer analysis indicated association of the IgM paraprotein with VWF before, but not after plasmapheresis, resulting in destruction of the agarose gel and a characteristically distorted band structure of VWF multimers. A type-2 pattern with highly abnormal VWF triplets and laboratory evidence of excessive fibrinolytic activity suggested that plasmin-mediated VWF degradation contributed to AVWS in a patient with multiple myeloma (MM) and AL amyloidosis. Finally, in a patient with IgG MM, maximally prolonged PFA-100® closure times and a specific defect in ristocetin-induced platelet agglutination, both of which resolved after remission induction, indicated interference of the paraprotein with VWF binding to platelet GPIb. Importantly, in none of the six patients, circulating autoantibodies to VWF were detected by a specific in-house ELISA. In summary, when evaluating PCD patients with severe bleeding symptoms, AVWS due to various pathogenic mechanisms should be considered. PMID:27040683

  18. A case of CD10-negative angioimmunoblastic T cell lymphoma with leukemic change and increased plasma cells mimicking plasma cell leukemia: A case report

    PubMed Central

    ADACHI, YASUSHI; HINO, TAKUYA; OHSAWA, MASAHIKO; UEKI, KAZUHITO; MURAO, TOMOKO; LI, MING; CUI, YUNZE; OKIGAKI, MITSUHIKO; ITO, MITSUHIRO; IKEHARA, SUSUMU

    2015-01-01

    Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c-Maf-1. Hypergammaglobulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10-negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78-year-old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood. Initially, plasma cell leukemia was suspected, due to the extreme increase in the number of plasma cells in the peripheral blood. However, the plasma cells did not show clonal expansion on examination by flow cytometry. Based on histological analyses, following a biopsy of an enlarged lymph node, the patient was diagnosed with AITL. This case suggests that when hypergammaglobulinemia and increases in B-lineage cells are observed, AITL should be considered in addition to disorders of B-lineage cells. PMID:26622708

  19. Immunosuppressive plasma cells impede T cell-dependent immunogenic chemotherapy

    PubMed Central

    Shalapour, Shabnam; Font-Burgada, Joan; Di Caro, Giuseppe; Zhong, Zhenyu; Sanchez-Lopez, Elsa; Dhar, Debanjan; Willimsky, Gerald; Ammirante, Massimo; Strasner, Amy; Hansel, Donna E.; Jamieson, Christina; Kane, Christopher J.; Klatte, Tobias; Birner, Peter; Kenner, Lukas; Karin, Michael

    2015-01-01

    Cancer-associated genetic alterations induce expression of tumor antigens which can activate CD8+ cytotoxic T cells (CTL), but the microenvironment of established tumors promotes immune tolerance through poorly understood mechanisms1,2. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumor-directed CTL and are effective in some human cancers1. Immune mechanisms also affect treatment outcome and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death (ICD) and other effector mechanisms3,4. Our previous studies revealed that B lymphocytes recruited by CXCL13 into prostate cancer (PC) promote castrate-resistant PC (CRPC) by producing lymphotoxin (LT) which activates an IKKα-Bmi1 module in PC stem cells5,6. Since CRPC is refractory to most therapies, we examined B cell involvement in acquisition of chemotherapy resistance. We focused this study on oxaliplatin, an immunogenic chemotherapeutic3,4 that is effective in aggressive PC7. We found that B cells modulate the response to low dose oxaliplatin, which by inducing ICD promotes tumor-directed CTL activation. Three different mouse PC models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The critical immunosuppressive B cells are plasmocytes that express IgA, IL-10 and PD-L1, whose appearance depends on TGFβ-receptor (TGFβR) signaling. Elimination of these cells, which also infiltrate human therapy-resistant PC, allows CTL-dependent eradication of oxaliplatin-treated tumors. PMID:25924065

  20. DNA damage and mitochondria dysfunction in cell apoptosis induced by nonthermal air plasma

    SciTech Connect

    Kim, G. J.; Lee, J. K.; Kim, W.; Kim, K. T.

    2010-01-11

    Nonthermal plasma is known to induce animal cell death but the mechanism is not yet clear. Here, cellular and biochemical regulation of cell apoptosis is demonstrated for plasma treated cells. Surface type nonthermal air plasma triggered apoptosis of B16F10 mouse melanoma cancer cells causing DNA damage and mitochondria dysfunction. Plasma treatment activated caspase-3, apoptosis executioner. The plasma treated cells also accumulated gamma-H2A.X, marker for DNA double strand breaks, and p53 tumor suppressor gene as a response to DNA damage. Interestingly, cytochrome C was released from mitochondria and its membrane potential was changed significantly.

  1. DNA damage and mitochondria dysfunction in cell apoptosis induced by nonthermal air plasma

    NASA Astrophysics Data System (ADS)

    Kim, G. J.; Kim, W.; Kim, K. T.; Lee, J. K.

    2010-01-01

    Nonthermal plasma is known to induce animal cell death but the mechanism is not yet clear. Here, cellular and biochemical regulation of cell apoptosis is demonstrated for plasma treated cells. Surface type nonthermal air plasma triggered apoptosis of B16F10 mouse melanoma cancer cells causing DNA damage and mitochondria dysfunction. Plasma treatment activated caspase-3, apoptosis executioner. The plasma treated cells also accumulated gamma-H2A.X, marker for DNA double strand breaks, and p53 tumor suppressor gene as a response to DNA damage. Interestingly, cytochrome C was released from mitochondria and its membrane potential was changed significantly.

  2. Biomedical Applications of Low Temperature Atmospheric Pressure Plasmas to Cancerous Cell Treatment and Tooth Bleaching

    NASA Astrophysics Data System (ADS)

    Lee, Jae Koo; Kim, Myoung Soo; Byun, June Ho; Kim, Kyong Tai; Kim, Gyoo Cheon; Park, Gan Young

    2011-08-01

    Low temperature atmospheric pressure plasmas have attracted great interests and they have been widely applied to biomedical applications to interact with living tissues, cells, and bacteria due to their non-thermal property. This paper reviews the biomedical applications of low temperature atmospheric pressure plasmas to cancerous cell treatment and tooth bleaching. Gold nanoparticles conjugated with cancer-specific antibodies have been introduced to cancerous cells to enhance selective killing of cells, and the mechanism of cell apoptosis induced by plasma has been investigated. Tooth exposed to helium plasma jet with hydrogen peroxide has become brighter and the productions of hydroxyl radicals from hydrogen peroxide have been enhanced by plasma exposure.

  3. Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies.

    PubMed

    Caltagirone, Simona; Ruggeri, Marina; Aschero, Simona; Gilestro, Milena; Oddolo, Daniela; Gay, Francesca; Bringhen, Sara; Musolino, Caterina; Baldini, Luca; Musto, Pellegrino; Petrucci, Maria T; Gaidano, Gianluca; Passera, Roberto; Bruno, Benedetto; Palumbo, Antonio; Boccadoro, Mario; Omedè, Paola

    2014-10-01

    Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19(+)/CD117(-) immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19(+)/CD117(-) bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #NCT01063179. PMID:25015938

  4. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    PubMed

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM. PMID:26758672

  5. The effect of jet and DBD plasma on NCI-78 blood cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Nagendra K.; Kaushik, Neha; Choi, Eun Ha

    2013-06-01

    In this study we describe the effects of a nonthermal jet and dielectric barrier discharge (DBD) plasma on the T98G brain cancer cell line. The results of this study reveal that the jet and DBD plasma inhibits NCI-78 blood cancer cells growth efficiently with the loss of metabolic viability of cells. The main goal of this study is to induce cell death in NCI-78 blood cancer cells by the toxic effect of jet and DBD plasma.

  6. Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells.

    PubMed

    Pan, Chendong; Nelson, Matthew S; Reyes, Morayma; Koodie, Lisa; Brazil, Joseph J; Stephenson, Elliot J; Zhao, Robert C; Peters, Charles; Selleck, Scott B; Stringer, Sally E; Gupta, Pankaj

    2005-09-15

    In mucopolysaccharidosis-I (MPS-I), alpha-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2-FGFR1-HS interactions, resulting in defective FGF-2-induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS-cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate. PMID:15947088

  7. Fat, Stem Cells, and Platelet-Rich Plasma.

    PubMed

    James, Isaac B; Coleman, Sydney R; Rubin, J Peter

    2016-07-01

    The ideal filler for aesthetic surgery is inexpensive and easy to obtain, natural in appearance and texture, immunologically compatible, and long lasting without risk of infection. By most metrics, autologous fat grafts meet these criteria perfectly. Although facial fat grafting is now a commonly accepted surgical procedure, there has been a wave of activity applying stem cells and platelet-rich plasma (PRP) therapies to aesthetic practice. This article addresses technical considerations in the use of autologous fat transfer for facial rejuvenation, and also explores the current evidence for these stem cell and PRP therapies in aesthetic practice. PMID:27363761

  8. Persistence of Cytogenetic Abnormalities at Complete Remission After Induction in Patients With Acute Myeloid Leukemia: Prognostic Significance and the Potential Role of Allogeneic Stem-Cell Transplantation

    PubMed Central

    Chen, Yiming; Cortes, Jorge; Estrov, Zeev; Faderl, Stefan; Qiao, Wei; Abruzzo, Lynne; Garcia-Manero, Guillermo; Pierce, Sherry; Huang, Xuelin; Kebriaei, Partow; Kadia, Tapan; De Lima, Marcos; Kantarjian, Hagop; Ravandi, Farhad

    2011-01-01

    Purpose To determine the prognostic impact of persistent cytogenetic abnormalities at complete remission (CR) on relapse-free survival (RFS) and overall survival (OS) in patients with acute myeloid leukemia (AML) and to examine the potential role of allogeneic stem-cell transplantation (SCT) in this setting. Patients and Methods Data from 254 adult patients with AML (excluding acute promyelocytic leukemia) who achieved CR after induction chemotherapy on various first-line protocols were examined. Results Median follow-up for surviving patients was 43 months. Patients with cytogenetic abnormalities at CR (n = 71) had significantly shorter RFS (P = .001) and OS (P < .001) compared with patients with normal cytogenetics at CR (n = 183); 3-year RFS was 15% and 45%, and 3-year OS was 15% and 56%, respectively. Among the patients with persistent cytogenetic abnormalities at CR, those who underwent SCT in first CR (CR1; n = 15) had better RFS and OS compared to those without SCT (n = 56; P = .04 and .06, respectively). In multivariate analysis, persistent cytogenetic abnormalities at CR was an independent predictor for RFS (P < .001) and OS (P = .001), but among patients with persistent cytogenetic abnormalities at CR, no significant differences in OS (P = .25) was observed between those who did or did not receive SCT with a trend favoring SCT for RFS (P = .08). Conclusion Persistent cytogenetically abnormal cells at CR predict a significantly shorter RFS and OS. SCT in CR1 may improve the clinical outcome of patients lacking cytogenetic remission after induction although this depends on patient selection. PMID:21555694

  9. Increased Plasma miRNA-30a as a Biomarker for Non-Small Cell Lung Cancer

    PubMed Central

    Sun, Ling; Chen, Yifan; Su, Qiaoli; Tang, Xiaoju; Liang, Yasha; Che, Guowei; Luo, Fengming

    2016-01-01

    Background MicroRNA (miRNA) is a small, non-coding RNA molecule which plays a role in the carcinogenesis and progression of cancers. Abnormal expression of miRNA in plasma has been found in some patients with malignant tumors. Material/Methods This study was conducted to investigate the expression of miRNA-30a in plasma of patients with non-small cell lung cancer (NSCLC). The plasma miRNA-30a in 87 patients with NSCLC, 20 patients with benign lung diseases, and 76 healthy subjects were measured by real-time PCR. The diagnostic value of miRNA-30a in NSCLC was evaluated via the ROC curve method. Results Plasma miRNA-30a level was significantly higher in the NSCLC group compared with benign control and healthy control groups (P<0.01). No statistically significant difference was found in the expression level of miRNA-30a among various clinical pathologic features in NSCLC. ROC curve analysis showed that the specificity and sensitivity cut-off points were at 61.0% and 84.3% for NSCLC. The specificity and sensitivity values were 54.9% and 94.4%, respectively, in the analysis based on in-patients only. Conclusions All these results suggest that plasma miRNA-30a measurement may be a novel and noninvasive method for NSCLC preliminary screening and differential diagnosis. PMID:26918265

  10. Plasma Cell-Free DNA in Paediatric Lymphomas

    PubMed Central

    Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

    2013-01-01

    Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

  11. Effect of non-thermal atmospheric pressure plasma jet on human breast cancer cells

    NASA Astrophysics Data System (ADS)

    Mirpour, Shahriar; Nikkhah, Maryam; Pirouzmand, Somaye; Ghomi, Hamid Reza

    2012-10-01

    Nowadays, Non-thermal plasma enjoy a wide range of applications in biomedical fields such as Sterilization, Wound healing, Cancer treatment and etc. The aim of this paper is to study the effect of non-thermal atmospheric pressure plasma jet on breast cancer (MCF-7) cells. In this regard the effect of plasma on death of the cancer cells are explored experimentally. The plasma in this discharge is created by pulsed dc high voltage power supply with repetition rate of several tens of kilohertz which led to the inductively coupled plasma. The pure helium gas were used for formation of the plasma jet. MTT assay were used for quantification of death cells. The results showed that the cells death rate increase with plasma exposure time. This study confirm that plasma jet have significant effect on treatment of human breast cancer cells.

  12. Efficacy and Mechanism of a Glycoside Compound Inhibiting Abnormal Prion Protein Formation in Prion-Infected Cells: Implications of Interferon and Phosphodiesterase 4D-Interacting Protein

    PubMed Central

    Nishizawa, Keiko; Oguma, Ayumi; Kawata, Maki; Sakasegawa, Yuji; Teruya, Kenta

    2014-01-01

    ABSTRACT A new type of antiprion compound, Gly-9, was found to inhibit abnormal prion protein formation in prion-infected neuroblastoma cells, in a prion strain-independent manner, when the cells were treated for more than 1 day. It reduced the intracellular prion protein level and significantly modified mRNA expression levels of genes of two types: interferon-stimulated genes were downregulated after more than 2 days of treatment, and the phosphodiesterase 4D-interacting protein gene, a gene involved in microtubule growth, was upregulated after more than 1 day of treatment. A supplement of interferon given to the cells partly restored the abnormal prion protein level but did not alter the normal prion protein level. This interferon action was independent of the Janus activated kinase-signal transducer and activator of transcription signaling pathway. Therefore, the changes in interferon-stimulated genes might be a secondary effect of Gly-9 treatment. However, gene knockdown of phosphodiesterase 4D-interacting protein restored or increased both the abnormal prion protein level and the normal prion protein level, without transcriptional alteration of the prion protein gene. It also altered the localization of abnormal prion protein accumulation in the cells, indicating that phosphodiesterase 4D-interacting protein might affect prion protein levels by altering the trafficking of prion protein-containing structures. Interferon and phosphodiesterase 4D-interacting protein had no direct mutual link, demonstrating that they regulate abnormal prion protein levels independently. Although the in vivo efficacy of Gly-9 was limited, the findings for Gly-9 provide insights into the regulation of abnormal prion protein in cells and suggest new targets for antiprion compounds. IMPORTANCE This report describes our study of the efficacy and potential mechanism underlying the antiprion action of a new antiprion compound with a glycoside structure in prion-infected cells, as well as

  13. Clonal evolution and tumor progression in 2 human colorectal adenoma-derived cell-lines invitro - the involvement of chromosome-1 abnormalities.

    PubMed

    Hague, A; Hanlon, K; Paraskeva, C

    1992-07-01

    Two human colorectal adenoma cell lines, S/RG and S/AN, have been continuously passaged in vitro to determine whether they would immortalize and if specific cytogenetic changes were involved in immortalization and tumor progression. At passage 7, S/RG was highly aneuploid, but had no abnormalities of chromosome 1 (Paraskeva et al, Cancer Res 49: 1282-1286, 1989). With continued passage under two independent sets of growth conditions an isochromosome Iq and derivatives of this isochromosome occurred as specific abnormalities. S/AN was near-diploid at passage 10, with a deletion in lp and monosomy 18. The karyotype at passage 44 showed no change. The cell lines are stable in that they have remained anchorage-dependent and non-tumorigenic after several years in culture and S/AN has retained a near diploid karyotype. These cell lines are therefore highly valuable for further studies of tumor progression in human colorectal carcinogenesis. PMID:21584532

  14. The Effect of Tuning Cold Plasma Composition on Glioblastoma Cell Viability

    PubMed Central

    Cheng, Xiaoqian; Sherman, Jonathan; Murphy, William; Ratovitski, Edward; Canady, Jerome; Keidar, Michael

    2014-01-01

    Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that the cold plasma induced cell death. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. In this paper, we seek to determine a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of the plasma, including treatment time, voltage, flow-rate and plasma-gas composition. In order to determine the threshold of plasma treatment on U87, normal human astrocytes (E6/E7) were used as the comparison cell line. Our data showed that the 30 sec plasma treatment caused 3-fold cell death in the U87 cells compared to the E6/E7 cells. All the other compositions of cold plasma were performed based on this result: plasma treatment time was maintained at 30 s per well while other plasma characteristics such as voltage, flow rate of source gas, and composition of source gas were changed one at a time to vary the intensity of the reactive species composition in the plasma jet, which may finally have various effect on cells reflected by cell viability. We defined a term “plasma dosage” to summarize the relationship of all the characteristics and cell viability. PMID:24878760

  15. Native fluorescence characterization of human liver abnormalities

    NASA Astrophysics Data System (ADS)

    Ganesan, Singaravelu; Madhuri, S.; Aruna, Prakasa R.; Suchitra, S.; Srinivasan, T. G.

    1999-05-01

    Fluorescence spectroscopy of intrinsic biomolecules has been extensively used in biology and medicine for the past several decades. In the present study, we report the native fluorescence characteristics of blood plasma from normal human subjects and patients with different liver abnormalities such as hepatitis, leptospirosis, jaundice, cirrhosis and liver cell failure. Native fluorescence spectra of blood plasma -- acetone extract were measured at 405 nm excitation. The average spectrum of normal blood plasma has a prominent emission peak around 464 nm whereas in the case of liver diseased subjects, the primary peak is red shifted with respect to normal. In addition, liver diseased cases show distinct secondary emission peak around 615 nm, which may be attributed to the presence of endogenous porphyrins. The red shift of the prominent emission peak with respect to normal is found to be maximum for hepatitis and minimum for cirrhosis whereas the secondary emission peak around 615 nm was found to be more prominent in the case of cirrhosis than the rest. The ratio parameter I465/I615 is found to be statistically significant (p less than 0.001) in discriminating liver abnormalities from normal.

  16. An antigenic study of human plasma cells in normal tissue and in myeloma: identification of a novel plasma cell associated antigen.

    PubMed Central

    Nathan, P D; Walker, L; Hardie, D; Richardson, P; Khan, M; Johnson, G D; Ling, N R

    1986-01-01

    A mouse monoclonal antibody named BU11 which detects an antigen strongly expressed on human plasma cells is described. The antibody stains plasma cells in tonsil sections, fresh and cultured plasmacytoid cells from the bone marrow of patients with multiple myeloma and cells of the plasmacytoid cell line RPMI 8226 used as the immunogen. In vitro studies of pokeweed mitogen (PWM) stimulated peripheral blood B cells and Epstein-Barr virus (EBV) stimulated tonsil B cells show that the antigen is present mainly on cells coexpressing the OKT10 antigen and containing cytoplasmic immunoglobulin (cIg). The BU11 antigen is expressed weakly on some normal B cells and is not present on T cells, monocytes or granulocytes. The antigen is of molecular weight 58kD under reducing conditions and is biochemically distinct from previously described plasma cell antigens. Images Fig. 4 PMID:3024883

  17. The effect of the suspension cells in plasma gene transfection method

    NASA Astrophysics Data System (ADS)

    Isozaki, Yuki; Nakano, Koki; Ikeda, Yoshihisa; Motomura, Hideki; Kido, Yugo; Satoh, Susumu; Tachibana, Kunihide; Jinno, Masafumi

    2015-09-01

    Plasma gene transfection method is a unique technique for introducing nucleic acids into cells by using plasma irradiation. In our previous works, plasma gene transfection method was performed for the adherent cells, e.g. COS-7 cells, and the influence of plasma on gene transfection has been investigated. As a next step for plasma medicine, transfection to much more various kinds of target cells is required. In this study, the authors attempted gene transfection to two kinds of suspension and four kinds of adherent cells. Although the transfection ratios to the suspension cells were low, transfection to all the kinds of cells were validated. To upregulate the transfection ratio for suspension cells, the authors are validating related factors by plasma irradiation. This work was partly supported by JSPS KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Number 25108509, 15H00896) and a grant from Ehime University.

  18. Mass Spectrometry Identification of Potential Mediators of Progestin-only Contraceptive Induced Abnormal Uterine Bleeding in Human Endometrial Stromal Cells

    PubMed Central

    Shapiro, John P.; Basar, Murat; Kayisli, Umit A.; Guzeloglu-Kayisli, Ozlem; Huang, S. Joseph; Suarez, Adrian A.; Ozer, Hatice Gulcin; Schatz, Frederick; Lockwood, Charles J.

    2015-01-01

    Objective Thrombin and hypoxia each target human endometrial stromal cells (HESCs) to mediate long-acting progestin-only contraceptive (LAPC) induced abnormal uterine bleeding (AUB). Thus, the secretome resulting from treatment of primary cultures of HESCs with thrombin or hypoxia was screened by mass spectrometry (MS) to detect potential protein mediators that lead to AUB. Study Design Cultured HESCs were primed with estradiol ± medroxyprogesterone acetate (MPA) or etonorgestrel (ETO), the respective progestins in MPA injected and ETO implanted LAPCs, and then treated by incubation with thrombin or under hypoxia. Collected conditioned medium supernatants were used for protein identification and quantitation of potential AUB mediators by liquid chromatography combined with tandem MS analysis. Microarray analysis of parallel cultures and immunostaining of endometrial biopsies of LAPC users vs. non-users corroborated MS results. Results MS identified several proteins displaying changes in expression levels from either thrombin or hypoxia treatments that are integral to angiogenesis or extracellular matrix formation. Several MS identified proteins were confirmed by mRNA microarray analysis. Over expressed stanniocalcin-1 (STC-1) was observed in endometrium of LAPC users. Unlike controls, all LAPC users displayed endometrial tubal metaplasia (ETM). Conclusions MS analysis identified many proteins that can affect angiogenesis or vessel integrity, thereby contributing to AUB. Confirmation of STC-1 overexpression in LAPC users and microarray data supports the validity of the MS data and suggests STC-1 involvement in AUB. The discovery of ETM in LAPC users indicates that LAPC-related side effects extend beyond AUB. The results presented here demonstrate a complex biological response to LAPC use. PMID:25529278

  19. The hormesis effect of plasma-elevated intracellular ROS on HaCaT cells

    NASA Astrophysics Data System (ADS)

    Szili, Endre J.; Harding, Frances J.; Hong, Sung-Ha; Herrmann, Franziska; Voelcker, Nicolas H.; Short, Robert D.

    2015-12-01

    We have examined the link between ionized-gas plasma delivery of reactive oxygen species (ROS) to immortalized keratinocyte (HaCaT) cells and cell fate, defined in terms of cell viability versus death. Phospholipid vesicles were used as cell mimics to measure the possible intracellular ROS concentration, [ROSi], delivered by various plasma treatments. Cells were exposed to a helium cold atmospheric plasma (CAP) jet for different plasma exposure times (5-60 s) and gas flow rates (50-1000 ml min-1). Based upon the [ROSi] data we argue that plasma-generated ROS in the cell culture medium can readily diffuse into real cells. Plasma exposure that equated to an [ROSi] in the range of 3.81  ×  10-10-9.47  ×  10-8 M, measured at 1 h after the plasma exposure, resulted in increased cell viability at 72 h; whereas a higher [ROSi] at 1 h decreased cell viability after 72 h of culture. This may be because of the manner in which the ROS are delivered by the plasma: HaCaT cells better tolerate a low ROS flux over an extended plasma exposure period of 1 min, compared to a high flux delivered in a few seconds, although the final [ROSi] may be the same. Our results suggest that plasma stimulation of HaCaT cells follows the principle of hormesis.

  20. High-contrast plasma-electrode Pockels cell

    SciTech Connect

    Kruschwitz, B. E.; Kelly, J. H.; Shoup, M. J. III; Waxer, L. J.; Cost, E. C.; Green, E. T.; Hoyt, Z. M.; Taniguchi, J.; Walker, T. W

    2007-03-10

    A plasma-electrode Pockels cell (PEPC) has been developed for use on the OMEGA extended performance (EP)laser system that can be used in a high-contrast optical switch, as required for isolation of the system from retroreflected pulses. Contrast ratios reliably exceeded 500:1 locally everywhere in the clear aperture. The key to achieving this improvement was the use of circular windows simply supported on compliant O rings, which is shown to produce very low stress-induced birefringence despite vacuum loading. Reliable operation was achieved operating at a relatively high operating pressure, low operating pressures being found to be strongly correlated to occurrences of local loss of plasma density.

  1. Detecting protein association at the T cell plasma membrane.

    PubMed

    Baumgart, Florian; Schütz, Gerhard J

    2015-04-01

    At the moment, many models on T cell signaling rely on results obtained via rather indirect methodologies, which makes direct comparison and conclusions to the in vivo situation difficult. Recently, a variety of new imaging methods were developed, which have the potential to directly shed light onto the mysteries of protein association at the T cell membrane. While the new modalities are extremely promising, for a broad readership it may be difficult to judge the results, since technological shortcomings are not always obvious. In this review article, we put key questions on the mechanism of protein interactions in the T cell plasma membrane into relation with techniques that allow to address such questions. We discuss applicability of the techniques, their strengths and weaknesses. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. PMID:25300585

  2. Plasma cells composing plasmacytoma have phenotypes different from those of myeloma cells.

    PubMed

    Sakai, A; Fujii, T; Noda, M; Hyodo, H; Oda, K; Kimura, A

    1996-12-01

    We describe one relapsed case of plasmacytoma of mandibular bone. The organs of relapse were liver and bone marrow. At relapse, monoclonal gammopathy (IgG-kappa) was observed without suppression of IgA and IgM. By immunostaining, the plasma cells of both the original mandibular bone and liver were positive for the same cytoplasmic immunoglobulin light chain kappa. The proliferative plasma cells in the bone marrow had the phenotype of CD38+, CD19+, and CD56- by flow cytometry and showed the presence of the rearranged IgH gene by Southern blotting. In addition, the zone of the Ig class of the patient's serum was not so sharply defined by zone electrophoresis. These results suggest that the characteristics of plasma cells of plasmacytoma are different from those of multiple myeloma. PMID:8948665

  3. Micro-Biocidal Activity of Yeast Cells by Needle Plasma Irradiation at Atmospheric Pressure

    NASA Astrophysics Data System (ADS)

    Kurumi, Satoshi; Takahashi, Hideyuki; Taima, Tomohito; Suzuki, Kaoru; Hirose, Hideharu; Masutani, Shigeyuki

    In this study, we report on the biocidal activity technique by needle helium plasma irradiation at atmospheric pressure using borosilicate capillary nozzle to apply for the oral surgery. The diameter of needle plasma was less than 50 µm, and temperature of plasma irradiated area was less than body temperature. Needle plasma showed emission due to OH and O radical. Raman spectra and methylene blue stain showed yeast cells were inactivated by needle plasma irradiation.

  4. 3D Mapping of plasma effective areas via detection of cancer cell damage induced by atmospheric pressure plasma jets

    NASA Astrophysics Data System (ADS)

    Han, Xu; Liu, Yueing; Stack, M. Sharon; Ptasinska, Sylwia

    2014-12-01

    In the present study, a nitrogen atmospheric pressure plasma jet (APPJ) was used for irradiation of oral cancer cells. Since cancer cells are very susceptible to plasma treatment, they can be used as a tool for detection of APPJ-effective areas, which extended much further than the visible part of the APPJ. An immunofluorescence assay was used for DNA damage identification, visualization and quantification. Thus, the effective damage area and damage level were determined and plotted as 3D images.

  5. Non-thermal Plasma Induces Apoptosis in Melanoma Cells via Production of Intracellular Reactive Oxygen Species

    PubMed Central

    Sensenig, Rachel; Kalghatgi, Sameer; Cerchar, Ekaterina; Fridman, Gregory; Shereshevsky, Alexey; Torabi, Behzad; Arjunan, Krishna Priya; Podolsky, Erica; Fridman, Alexander; Friedman, Gary; Azizkhan-Clifford, Jane; Brooks, Ari D.

    2012-01-01

    Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p<0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm2. TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p<0.001) at a dose of 15 J/cm2. Pre-treatment with N-acetyl-L-cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm2. Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by γ-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies. PMID:21046465

  6. CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations.

    PubMed

    Arce, Sergio; Luger, Elke; Muehlinghaus, Gwendolin; Cassese, Giuliana; Hauser, Anja; Horst, Alexander; Lehnert, Katja; Odendahl, Marcus; Hönemann, Dirk; Heller, Karl-Dieter; Kleinschmidt, Harald; Berek, Claudia; Dörner, Thomas; Krenn, Veit; Hiepe, Falk; Bargou, Ralf; Radbruch, Andreas; Manz, Rudolf A

    2004-06-01

    Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38. CD38 low IgG-secreting cells were present exclusively in the tonsils. A major fraction of these cells appeared to be early plasma cell precursors, as upon activation of B cells in vitro, IgG secretion preceded up-regulation of CD38, and on tonsillar sections, IgG-containing, CD38 low cells with a plasmacytoid phenotype were found in follicles, where plasma cell differentiation starts. A unitary phenotype of migratory peripheral blood IgG-secreting cells suggests that all bone marrow plasma cell populations share a common precursor cell. These data are compatible with a multistep model for plasma cell differentiation and imply that a common CD38 low IgG-secreting precursor gives rise to a diverse plasma cell compartment. PMID:15020647

  7. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals.

    PubMed

    Cassese, Giuliana; Arce, Sergio; Hauser, Anja E; Lehnert, Katja; Moewes, Beate; Mostarac, Miro; Muehlinghaus, Gwendolin; Szyska, Martin; Radbruch, Andreas; Manz, Rudolf A

    2003-08-15

    Recent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-alpha, and stromal cell-derived factor-1alpha as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements. As shown in IL-6-deficient mice, IL-6 is required for a normal induction, but not for the maintenance of plasma cell responses in vivo, indicating that the effects of individual survival factors are redundant. Optimal survival of isolated plasma cells requires stimulation by a combination of factors acting synergistically. These results strongly support the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1alpha, TNF-alpha, and ligands for CD44, provides an environment required to mediate plasma cell longevity. PMID:12902466

  8. Analysis of plasma membrane phosphoinositides from fusogenic carrot cells

    SciTech Connect

    Wheeler, J.J.; Boss, W.F.

    1987-04-01

    Phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP/sub 2/) were found to be associated with the plasma membrane-rich fractions isolated by aqueous polymer two-phase partitioning from fusogenic cells. They represented at least 5% and 0.7% of the total inositol-labeled lipids in the plasma membrane-rich fractions, respectively, and were present in a ratio of about 7:1 (PIP:PIP/sub 2/). In addition, two unidentified inositol-labeled compounds, which together were approximately 3% of the inositol-labeled lipids, were found predominantly in the plasma membrane-rich fractions and migrated between PIP/sub 2/ and PIP. The R/sub f/s of these compounds were approximately 0.31 and 0.34 in the solvent system CHCl/sub 3/:MeOH:15N NH/sub 4/OH:H/sub 2/O (90:90:7:22) using LK5 plates presoaked in 1% potassium oxalate. These compounds incorporated /sup 32/P/sub i/, (/sup 3/H)inositol and were hydrolyzed in mild base. These data suggested that they were glycero-phospholipids. Although the compounds did not comigrate with lysoPIP obtained from bovine brain (R/sub f/ approx. 0.35), when endogenous PIP was hydrolyzed to lysoPIP, the breakdown product migrated in the region of the unidentified inositol lipids.

  9. The effect of plasma on solar cell array arc characteristics

    NASA Technical Reports Server (NTRS)

    Snyder, D. B.; Tyree, E.

    1984-01-01

    The influence from the ambient plasma on the arc characteristics of a negatively biased solar cell array was investigated. The arc characteristics examined were the peak current during an arc, the decay time as the arc terminates, and the charge lost during the arc. These arc characteristics were examined in a nitrogen plasma with charge densities ranging from 15,000 to 45,000 cu cm. Background gas pressures ranged from 8x1,000,000 to 6x100,000 torr. Over these ranges of parameters no significant effect on the arc characteristics were seen. Arc characteristics were also examined for three gas species: helium, nitrogen and argon. The helium arcs have higher peak currents and shorter decay times than nitrogen and argon arcs. There are slight differences in the arc characteristics between nitrogen and argon. These differences may be caused by the differences in mass of the respective species. Also, evidence is presented for an electron emission mechanism appearing as a precursor to solar array arcs. Occassionally the plasma generator could be turned off, and currents could still be detected in the vacuum system. When these currents are presented, arcs may occur.

  10. Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM): expression of Fas ligand/Fas-mediated apoptosis signaling molecules in luteal cells.

    PubMed

    Kiso, Minako; Manabe, Noboru; Komatsu, Kohji; Shimabe, Munetake; Miyamoto, Hajime

    2003-12-01

    Senescence accelerated mouse-prone (SAMP) mice with a shortened life span show accelerated changes in many of the signs of aging and a shorter reproductive life span than SAM-resistant (SAMR) controls. We previously showed that functional regression (progesterone dissimilation) occurs in abnormally accumulated luteal bodies (aaLBs) of SAMP mice, but structural regression of luteal cells in aaLB is inhibited. A deficiency of luteal cell apoptosis causes the abnormal accumulation of LBs in SAMP ovaries. In the present study, to show the abnormality of Fas ligand (FasL)/Fas-mediated apoptosis signal transducing factors in the aaLBs of the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase-8 and caspase-3 mRNAs by reverse transcription-polymerase chain reaction, and in the expression and localization of FasL, Fas and activated caspase-3 proteins by Western blotting and immunohistochemistry, respectively, during the estrus cycle/luteolysis. These mRNAs and proteins were expressed in normal LBs of both SAMP and SAMR ovaries, but not at all or only in trace amounts in aaLBs of SAMP, indicating that structural regression is inhibited by blockage of the expression of these transducing factors in luteal cells of aaLBs in SAMP mice. PMID:14967896

  11. miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis.

    PubMed

    Norfo, Ruggiero; Zini, Roberta; Pennucci, Valentina; Bianchi, Elisa; Salati, Simona; Guglielmelli, Paola; Bogani, Costanza; Fanelli, Tiziana; Mannarelli, Carmela; Rosti, Vittorio; Pietra, Daniela; Salmoiraghi, Silvia; Bisognin, Andrea; Ruberti, Samantha; Rontauroli, Sebastiano; Sacchi, Giorgia; Prudente, Zelia; Barosi, Giovanni; Cazzola, Mario; Rambaldi, Alessandro; Bortoluzzi, Stefania; Ferrari, Sergio; Tagliafico, Enrico; Vannucchi, Alessandro M; Manfredini, Rossella

    2014-09-25

    Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by megakaryocyte (MK) hyperplasia, bone marrow fibrosis, and abnormal stem cell trafficking. PMF may be associated with somatic mutations in JAK2, MPL, or CALR. Previous studies have shown that abnormal MKs play a central role in the pathophysiology of PMF. In this work, we studied both gene and microRNA (miRNA) expression profiles in CD34(+) cells from PMF patients. We identified several biomarkers and putative molecular targets such as FGR, LCN2, and OLFM4. By means of miRNA-gene expression integrative analysis, we found different regulatory networks involved in the dysregulation of transcriptional control and chromatin remodeling. In particular, we identified a network gathering several miRNAs with oncogenic potential (eg, miR-155-5p) and targeted genes whose abnormal function has been previously associated with myeloid neoplasms, including JARID2, NR4A3, CDC42, and HMGB3. Because the validation of miRNA-target interactions unveiled JARID2/miR-155-5p as the strongest relationship in the network, we studied the function of this axis in normal and PMF CD34(+) cells. We showed that JARID2 downregulation mediated by miR-155-5p overexpression leads to increased in vitro formation of CD41(+) MK precursors. These findings suggest that overexpression of miR-155-5p and the resulting downregulation of JARID2 may contribute to MK hyperplasia in PMF. PMID:25097177

  12. Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis

    PubMed Central

    Akiyama, Yoshiyuki; Morikawa, Teppei; Maeda, Daichi; Shintani, Yukako; Niimi, Aya; Nomiya, Akira; Nakayama, Atsuhito; Igawa, Yasuhiko; Fukayama, Masashi; Homma, Yukio

    2016-01-01

    An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder. PMID:27339056

  13. Increased CXCR3 Expression of Infiltrating Plasma Cells in Hunner Type Interstitial Cystitis.

    PubMed

    Akiyama, Yoshiyuki; Morikawa, Teppei; Maeda, Daichi; Shintani, Yukako; Niimi, Aya; Nomiya, Akira; Nakayama, Atsuhito; Igawa, Yasuhiko; Fukayama, Masashi; Homma, Yukio

    2016-01-01

    An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of Hunner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder. PMID:27339056

  14. In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.

    PubMed

    Geisler, C H; Philip, P; Christensen, B E; Hou-Jensen, K; Pedersen, N T; Jensen, O M; Thorling, K; Andersen, E; Birgens, H S; Drivsholm, A; Ellegaard, J; Larsen, J K; Plesner, T; Brown, P; Andersen, P K; Hansen, M M

    1997-01-01

    Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5+, Slg(weak), mainly FMC7-) and atypical for CLL in 122 patients (25%) (CD5-, or Slg(strong) or FMC7+). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12complex, 14q+, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q+, an abnormal karyotype, +12complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype. We conclude that in patients with typical CLL immunophenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12complex, 14q+, del 6q and chromosome 17 are found in about 50% of the

  15. Simplex-in-cell technique for collisionless plasma simulations

    NASA Astrophysics Data System (ADS)

    Kates-Harbeck, Julian; Totorica, Samuel; Zrake, Jonathan; Abel, Tom

    2016-01-01

    We extend the simplex-in-cell (SIC) technique recently introduced in the context of collisionless dark matter fluids [1,2] to the case of collisionless plasmas. The six-dimensional phase space distribution function f (x , v) is represented by an ensemble of three-dimensional manifolds, which we refer to as sheets. The electric potential field is obtained by solving the Poisson equation on a uniform mesh, where the charge density is evaluated by a spatial projection of the phase space sheets. The SIC representation of phase space density facilitates robust, high accuracy numerical evolution of the Vlasov-Poisson system using significantly fewer tracer particles than comparable particle-in-cell (PIC) approaches by reducing the numerical shot-noise associated with the latter. We introduce the SIC formulation and describe its implementation in a new code, which we validate using standard test problems including plasma oscillations, Landau damping, and two stream instabilities in one dimension. Merits of the new scheme are shown to include higher accuracy and faster convergence rates in the number of particles. We finally motivate and outline the efficient application of SIC to higher dimensional problems.

  16. B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas.

    PubMed

    Li, Shaoying; Seegmiller, Adam C; Lin, Pei; Wang, Xuan J; Miranda, Roberto N; Bhagavathi, Sharathkumar; Medeiros, L Jeffrey

    2015-02-01

    Large B-cell lymphomas with IGH@BCL2 and MYC rearrangement, known as double-hit lymphoma (DHL), are clinically aggressive neoplasms with a poor prognosis. Some large B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about patients with these lymphomas designated here as atypical DHL. We studied 40 patients of atypical DHL including 21 men and 19 women, with a median age of 60 years. Nine (23%) patients had a history of B-cell non-Hodgkin lymphoma. There were 30 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 3 DLBCL with coexistent follicular lymphoma. CD10, BCL2, and MYC were expressed in 28/39 (72%), 33/35 (94%), and 14/20 (70%) cases, respectively. Patients were treated with standard (n=14) or more aggressive chemotherapy regimens (n=17). We compared the atypical DHL group with 76 patients with DHLand 35 patients with DLBCL lacking MYC and BCL2 abnormalities. The clinicopathologic features and therapies were similar between patients with atypical and typical DHL. The overall survival of patients with atypical double-hit lymphoma was similar to that of patients with double-hit lymphoma (P=0.47) and significantly worse than that of patients with DLBCL with normal MYC and BCL2 (P=0.02). There were some minor differences. Cases of atypical double-hit lymphoma more often have DLBCL morphology (P<0.01), less frequently expressed CD10 (P<0.01), and patients less often had an elevated serum lactate dehydrogenase level (P=0.01). In aggregate, these results support expanding the category of MYC/BCL2 DHL to include large B-cell lymphomas with coexistent MYC and BCL2 abnormalities other than concurrent translocations. PMID:25103070

  17. Characterization of plasma-induced cell membrane permeabilization: focus on OH radical distribution

    NASA Astrophysics Data System (ADS)

    Sasaki, Shota; Honda, Ryosuke; Hokari, Yutaro; Takashima, Keisuke; Kanzaki, Makoto; Kaneko, Toshiro

    2016-08-01

    Non-equilibrium atmospheric-pressure plasma (APP) is used medically for plasma-induced cell permeabilization. However, how plasma irradiation specifically triggers permeabilization remains unclear. In an attempt to identify the dominant factor(s), the distribution of plasma-produced reactive species was investigated, primarily focusing on OH radicals. A stronger plasma discharge, which produced more OH radicals in the gas phase, also produced more OH radicals in the liquid phase (OHaq), enhancing the cell membrane permeability. In addition, plasma irradiation-induced enhancement of cell membrane permeability decreased markedly with increased solution thickness (<1 mm), and the plasma-produced OHaq decayed in solution (diffusion length on the order of several hundred micrometers). Furthermore, the horizontally center-localized distribution of OHaq corresponded with the distribution of the permeabilized cells by plasma irradiation, while the overall plasma-produced oxidizing species in solution (detected by iodine-starch reaction) exhibited a doughnut-shaped horizontal distribution. These results suggest that OHaq, among the plasma-produced oxidizing species, represents the dominant factor in plasma-induced cell permeabilization. These results enhance the current understanding of the mechanism of APP as a cell-permeabilization tool.

  18. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

    2012-02-01

    Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

  19. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  20. Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells

    PubMed Central

    Kim, Sun Ja; Chung, T. H.

    2016-01-01

    Cold atmospheric helium plasma jets were fabricated and utilized for plasma–cell interactions. The effect of operating parameters and jet design on the generation of specific reactive oxygen and nitrogen species (RONS) within cells and cellular response were investigated. It was found that plasma treatment induced the overproduction of RONS in various cancer cell lines selectively. The plasma under a relatively low applied voltage induced the detachment of cells, a reduction in cell viability, and apoptosis, while the plasma under higher applied voltage led to cellular necrosis in our case. To determine whether plasma-induced reactive oxygen species (ROS) generation occurs through interfering with mitochondria-related cellular response, we examined the plasma effects on ROS generation in both parental A549 cells and A549 ρ0 cells. It was observed that cancer cells were more susceptible to plasma-induced RONS (especially nitric oxide (NO) and nitrogen dioxide (NO2−) radicals) than normal cells, and consequently, plasma induced apoptotic cell responses mainly in cancer cells. PMID:26838306

  1. The interaction of atmospheric pressure plasma jets with cancer and normal cells: generation of intracellular reactive oxygen species and changes of the cell proliferation and cell cycle

    NASA Astrophysics Data System (ADS)

    Chung, Tae Hun; Joh, Hea Min; Kim, Sun Ja; Leem, Sun Hee

    2013-09-01

    The possibility of atmospheric pressure plasmas is emerging as a candidate in cancer therapy. The primary role is played by reactive oxygen species (ROS), UV photons, charged particles and electric fields. Among them, intracellular ROS induced by plasma are considered to be the key constituents that induce cellular changes and apoptosis. In this study, the effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. The plasma treatment was performed under different working gases, applied voltages, gas flow rates, and with and without additive oxygen flow. Using a detection dye, we observed that plasma exposure leads to the increase of the intracellular ROS and that the intracellular ROS production can be controlled by plasma parameters. A significant ROS generation was induced by plasma exposure on cancer cells and the overproduction of ROS contributes to the reduced cell proliferation. Normal cells were observed to be less affected by the plasma-mediated ROS and cell proliferation was less changed. The plasma treatment also resulted in the alteration of the cell cycle that contributes to the induction of apoptosis in cancer cells. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as cancer therapy. This work was supported by the National Research Foundation of Korea under Contract No. 2012R1A1A2002591 and 2012R1A1A3010213.

  2. Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade.

    PubMed

    Zhao, Yu; Li, Hang; Zhang, Yingyi; Li, Leilei; Fang, Runping; Li, Yinghui; Liu, Qian; Zhang, Weiying; Qiu, Liyan; Liu, Fabao; Zhang, Xiaodong; Ye, Lihong

    2016-08-15

    Abnormal lipid metabolism is a hallmark of tumorigenesis. Accumulating evidence demonstrates that fatty acid synthase (FAS, FASN) is a metabolic oncogene that supports the growth and survival of tumor cells and is highly expressed in many cancers. Here, we report that the oncoprotein, hepatitis B X-interacting protein (HBXIP, LAMTOR5) contributes to abnormal lipid metabolism. We show that high expression of HBXIP in 236 breast cancer patients was significantly associated with decreased overall survival and progression-free survival. Interestingly, the expression of HBXIP was positively related to that of FAS in clinical breast cancer tissues, and HBXIP overexpression in breast cancer cells resulted in FAS upregulation. Mechanistically, HBXIP upregulated SREBP-1c (SREBF1), which activates the transcription of FAS, by directly interacting with and coactivating nuclear receptor (NR) liver X receptors (LXR). Physiologically, LXRs are activated via a coactivator containing NR motif in a ligand-dependent manner. However, in breast cancer cells, HBXIP containing the corepressor/nuclear receptor motif with special flanking sequence could coactivate LXRs independent of ligand. Moreover, overexpressed SREBP-1c was able to activate the transcription of HBXIP, forming a positive-feedback loop. Functionally, HBXIP enhanced lipogenesis, resulting in the growth of breast cancer cells in vitro and in vivo Thus, we conclude that the oncoprotein HBXIP contributes to the abnormal lipid metabolism in breast cancer through LXRs/SREBP-1c/FAS signaling, providing new insights into the mechanisms by which cancer cells reprogram lipid metabolism in their favor. Cancer Res; 76(16); 4696-707. ©2016 AACR. PMID:26980761

  3. Focal Adhesion of Osteoblastic Cells on Titanium Surface with Amine Functionalities Formed by Plasma Polymerization

    NASA Astrophysics Data System (ADS)

    Song, Heesang; Jung, Sang Chul; Kim, Byung Hoon

    2012-08-01

    To enhance the focal adhesion of osteoblastic cells on a titanium surface, plasma polymerized allyl amine (AAm) thin films were deposited by plasma polymerization. This plasma polymer functionalization of titanium is advantageous for osteoblastic focal adhesion formation. Such Ti surfaces are useful for the fabrication of titanium-based dental implants for enhancement of osseointegration.

  4. Fluconazole treatment hyperpolarizes the plasma membrane of Candida cells.

    PubMed

    Elicharova, Hana; Sychrova, Hana

    2013-11-01

    Five pathogenic Candida species were compared in terms of their osmotolerance, tolerance to toxic sodium and lithium cations, and resistance to fluconazole. The species not only differed, in general, in their tolerance to high osmotic pressure (C. albicans and C. parapsilosis being the most osmotolerant) but exhibited distinct sensitivities to toxic sodium and lithium cations, with C. parapsilosis and C. tropicalis being very tolerant but C. krusei and C. dubliniensis sensitive to LiCl. The treatment of both fluconazole-susceptible (C. albicans and C. parapsilosis) and fluconazole-resistant (C. dubliniensis, C. krusei and C. tropicalis) growing cells with subinhibitory concentrations of fluconazole resulted in substantially elevated intracellular Na(+) levels. Using a diS-C3(3) assay, for the first time, to monitor the relative membrane potential (ΔΨ) of Candida cells, we show that the fluconazole treatment of growing cells of all five species results in a substantial hyperpolarization of their plasma membranes, which is responsible for an increased non-specific transport of toxic alkali metal cations and other cationic drugs (e.g., hygromycin B). Thus, the combination of relatively low doses of fluconazole and drugs, whose import into the tested Candida strains is driven by the cell membrane potential, might be especially potent in terms of its ability to inhibit the growth of or even kill various Candida species. PMID:23547882

  5. Effects of atmospheric pressure cold plasma on human hepatocarcinoma cell and its 5-fluorouracil resistant cell line

    SciTech Connect

    Yang, H.; Gan, L.; Yang, X. E-mail: yangxl@mail.hust.edu.cn; Lu, R.; Xian, Y.; Lu, X. E-mail: yangxl@mail.hust.edu.cn

    2015-12-15

    Atmospheric pressure cold plasma showed selective killing efficiency on cancer cells in vitro and in vivo, which makes plasma a potential option for cancer therapy. However, the plasma effects on chemotherapeutic drugs-resistant cells are rarely to be found. In this paper, the effects of plasma on human hepatocellular carcinoma Bel7402 cells and 5-fluorouracil (5-FU) resistant Bel7402/5FU cells were intensively investigated. The results showed that plasma induced superior toxicity to Bel7402 cells compared with Bel7402/5FU cells. Incubation with plasma-treated medium for 20 s induced more than 85% death rate in Bel7402 cells, while the same death ratio was achieved when Bel7402/5FU cells were treated for as long as 300 s. The hydrogen peroxide in the medium played a leading role in the cytotoxicity effects. Further studies implicated that when the treatment time was shorter than 60 s, the depolarization of mitochondrial membrane potential and apoptosis occurred through the intracellular reactive oxygen species accumulation in Bel7402 cells. Molecular analysis showed an increase in the transcription factor activity for AP-1, NF-kB, and p53 in Bel7402 cells. No obvious damage could be detected in plasma-treated Bel7402/5FU cells due to the strong intracellular reactive oxygen stress scavenger system.

  6. Effects of atmospheric pressure cold plasma on human hepatocarcinoma cell and its 5-fluorouracil resistant cell line

    NASA Astrophysics Data System (ADS)

    Yang, H.; Lu, R.; Xian, Y.; Gan, L.; Lu, X.; Yang, X.

    2015-12-01

    Atmospheric pressure cold plasma showed selective killing efficiency on cancer cells in vitro and in vivo, which makes plasma a potential option for cancer therapy. However, the plasma effects on chemotherapeutic drugs-resistant cells are rarely to be found. In this paper, the effects of plasma on human hepatocellular carcinoma Bel7402 cells and 5-fluorouracil (5-FU) resistant Bel7402/5FU cells were intensively investigated. The results showed that plasma induced superior toxicity to Bel7402 cells compared with Bel7402/5FU cells. Incubation with plasma-treated medium for 20 s induced more than 85% death rate in Bel7402 cells, while the same death ratio was achieved when Bel7402/5FU cells were treated for as long as 300 s. The hydrogen peroxide in the medium played a leading role in the cytotoxicity effects. Further studies implicated that when the treatment time was shorter than 60 s, the depolarization of mitochondrial membrane potential and apoptosis occurred through the intracellular reactive oxygen species accumulation in Bel7402 cells. Molecular analysis showed an increase in the transcription factor activity for AP-1, NF-кB, and p53 in Bel7402 cells. No obvious damage could be detected in plasma-treated Bel7402/5FU cells due to the strong intracellular reactive oxygen stress scavenger system.

  7. Haematological abnormalities in mitochondrial disorders

    PubMed Central

    Finsterer, Josef; Frank, Marlies

    2015-01-01

    INTRODUCTION This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as ‘definite’, ‘probable’ or ‘possible’ according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS A total of 46 patients (‘definite’ = 5; ‘probable’ = 9; ‘possible’ = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION MID should be considered if a patient’s abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes. Abnormal blood cell counts may be the sole manifestation of MID or a collateral feature of a multisystem problem. PMID:26243978

  8. Apoptotic effects on cultured cells of atmospheric-pressure plasma produced using various gases

    NASA Astrophysics Data System (ADS)

    Tominami, Kanako; Kanetaka, Hiroyasu; Kudo, Tada-aki; Sasaki, Shota; Kaneko, Toshiro

    2016-01-01

    This study investigated the effects of low-temperature atmospheric-pressure plasma on various cells such as rat fibroblastic Rat-1 cell line, rat neuroblastoma-like PC12 cell line, and rat macrophage-like NR8383 cell line. The plasma was irradiated directly to a culture medium containing plated cells for 0-20 s. The applied voltage, excitation frequency, and argon or helium gas flow were, respectively, 3-6 kV, 10 kHz, and 3 L/min. Cell viability and apoptotic activity were evaluated using annexin-V/propidium iodide staining. Results showed that the low-temperature atmospheric-pressure plasma irradiation promoted cell death in a discharge-voltage-dependent and irradiation-time-dependent manner. Furthermore, different effects are produced depending on the cell type. Moreover, entirely different mechanisms might be responsible for the induction of apoptosis in cells by helium and argon plasma.

  9. The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation.

    PubMed

    Carotta, Sebastian; Willis, Simon N; Hasbold, Jhagvaral; Inouye, Michael; Pang, Swee Heng Milon; Emslie, Dianne; Light, Amanda; Chopin, Michael; Shi, Wei; Wang, Hongsheng; Morse, Herbert C; Tarlinton, David M; Corcoran, Lynn M; Hodgkin, Philip D; Nutt, Stephen L

    2014-10-20

    Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation. PMID:25288399

  10. Cell volume and plasma membrane osmotic water permeability in epithelial cell layers measured by interferometry.

    PubMed Central

    Farinas, J; Verkman, A S

    1996-01-01

    The development of strategies to measure plasma membrane osmotic water permeability (Pf) in epithelial cells has been motivated by the identification of a family of molecular water channels. A general approach utilizing interferometry to measure cell shape and volume was developed and applied to measure Pf in cell layers. The method is based on the cell volume dependence of optical path length (OPL) for a light beam passing through the cell. The small changes in OPL were measured by interferometry. A mathematical model was developed to relate the interference signal to cell volume changes for cells of arbitrary shape and size. To validate the model, a Mach-Zehnder interference microscope was used to image OPL in an Madin Darby Canine Kidney (MDCK) cell layer and to reconstruct the three-dimensional cell shape (OPL resolution < lambda/25). As predicted by the model, a doubling of cell volume resulted in a change in OPL that was proportional to the difference in refractive indices between water and the extracellular medium. The time course of relative cell volume in response to an osmotic gradient was computed from serial interference images. To measure cell volume without microscopy and image analysis, a Mach-Zehnder interferometer was constructed in which one of two interfering laser beams passed through a flow chamber containing the cell layer. The interference signal in response to an osmotic gradient was analyzed to quantify the time course of relative cell volume. The calculated MDCK cell plasma membrane Pf of 6.1 x 10(-4) cm/s at 24 degrees C agreed with that obtained by interference microscopy and by a total internal reflection fluorescence method. Interferometry was also applied to measure the apical plasma membrane water permeability of intact toad urinary bladder; Pf increased fivefold after forskolin stimulation to 0.04 cm/s at 23 degrees C. These results establish and validate the application of interferometry to quantify cell volume and osmotic water

  11. Dopamine and T cells: dopamine receptors and potent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases.

    PubMed

    Levite, M

    2016-01-01

    Dopamine, a principal neurotransmitter, deserves upgrading to 'NeuroImmunotransmitter' thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent activator of resting effector T cells (Teffs), via two independent ways: direct Teffs activation, and indirect Teffs activation by suppression of regulatory T cells (Tregs). The review covers the following findings: (i) T cells express functional dopamine receptors (DRs) D1R-D5R, but their level and function are dynamic and context-sensitive, (ii) DR membranal protein levels do not necessarily correlate with DR mRNA levels, (iii) different T cell types/subtypes have different DR levels and composition and different responses to dopamine, (iv) autoimmune and pro-inflammatory T cells and T cell leukaemia/lymphoma also express functional DRs, (v) dopamine (~10(-8) M) activates resting/naive Teffs (CD8(+) >CD4(+) ), (vi) dopamine affects Th1/Th2/Th17 differentiation, (vii) dopamine inhibits already activated Teffs (i.e. T cells that have been already activated by either antigen, mitogen, anti-CD3 antibodies cytokines or other molecules), (viii) dopamine inhibits activated Tregs in an autocrine/paracrine manner. Thus, dopamine 'suppresses the suppressors' and releases the inhibition they exert on Teffs, (ix) dopamine affects intracellular signalling molecules and cascades in T cells (e.g. ERK, Lck, Fyn, NF-κB, KLF2), (x) T cells produce dopamine (Tregs>Teffs), can release dopamine, mainly after activation (by antigen, mitogen, anti-CD3 antibodies, PKC activators or other), uptake extracellular dopamine, and most probably need dopamine, (xi) dopamine is important for antigen-specific interactions between T cells and dendritic cells, (xii) in few autoimmune diseases (e.g. multiple sclerosis/SLE/rheumatoid arthritis), and neurological/psychiatric diseases (e.g. Parkinson disease, Alzheimer's disease, Schizophrenia and Tourette), patient's T cells seem to have abnormal DRs

  12. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    PubMed

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  13. Altered Antioxidant System Stimulates Dielectric Barrier Discharge Plasma-Induced Cell Death for Solid Tumor Cell Treatment

    PubMed Central

    Park, Daehoon; Choi, Eun H.

    2014-01-01

    This study reports the experimental findings and plasma delivery approach developed at the Plasma Bioscience Research Center, Korea for the assessment of antitumor activity of dielectric barrier discharge (DBD) for cancer treatment. Detailed investigation of biological effects occurring after atmospheric pressure non-thermal (APNT) plasma application during in vitro experiments revealed the role of reactive oxygen species (ROS) in modulation of the antioxidant defense system, cellular metabolic activity, and apoptosis induction in cancer cells. To understand basic cellular mechanisms, we investigated the effects of APNT DBD plasma on antioxidant defense against oxidative stress in various malignant cells as well as normal cells. T98G glioblastoma, SNU80 thyroid carcinoma, KB oral carcinoma and a non-malignant HEK293 embryonic human cell lines were treated with APNT DBD plasma and cellular effects due to reactive oxygen species were observed. Plasma significantly decreased the metabolic viability and clonogenicity of T98G, SNU80, KB and HEK293 cell lines. Enhanced ROS in the cells led to death via alteration of total antioxidant activity, and NADP+/NADPH and GSH/GSSG ratios 24 hours (h) post plasma treatment. This effect was confirmed by annexin V-FITC and propidium iodide staining. These consequences suggested that the failure of antioxidant defense machinery, with compromised redox status, might have led to sensitization of the malignant cells. These findings suggest a promising approach for solid tumor therapy by delivering a lethal dose of APNT plasma to tumor cells while sparing normal healthy tissues. PMID:25068311

  14. Pulsed Power Aspects of the NIF Plasma Electrode Pockels Cell

    SciTech Connect

    Arnold, P A; Ollis, C W; Hinz, A F; Barbosa, F; Fulkerson, E S

    2005-06-09

    The Plasma Electrode Pockels Cell (PEPC) embodies technology essential to the National Ignition Facility (NIF). Together with a thin-film polarizer, PEPC functions as an optical switch for the main amplifier cavity, allowing optical pulses to be trapped, and then released, and enabling NIF to take advantage of the attendant gain and cost-savings. Details of the genesis, development, and prototyping of the PEPC are well documented. After moving from its laboratory setting to the NIF facility, PEPC--via its performance during the two-year NIF Early Light (NEL) campaign and its ongoing operation during facility build-out--has proven to be a fully functional system. When complete, NIF will accommodate 192 beams, capable of delivering 1.8 MJ to a fusion target. Forty-eight Plasma Electrode Pockels--driven by nearly 300 high-power, high-voltage pulse generators--will support this complement of beams. As deployed, PEPC is a complex association of state-of-the-art optics; low-voltage and high-voltage electronics; and mechanical, gas, and vacuum subsystems--all under computer control. In this paper, we briefly describe each of these elements, but focus on the pulse power aspects of the PEPC system.

  15. Plasma RF Switching Elements for Cell Phone Applications

    NASA Astrophysics Data System (ADS)

    Linardakis, Peter; Borg, Gerard G.; Harris, Jeffrey H.

    2002-10-01

    The functionality of modern multi-band, multi-system cell phones is provided by a large number of RF switches. Future phones will require an even greater number of these switches to implement hardware such as agile antennas. The ever increasing need for higher performance and lower power consumption have brought the RF PIN diode to the edge of its capabilities in these applications. RF micro-electromechanical (MEMS) switches can easily provide the required low insertion loss, low inter-modulation and low power consumption combination, but their reliability limits are not yet satisfactory to industry. In conjunction with Motorola Personal Communications Sector (PCS), PRL is undertaking a project to examine the possibility of using plasma in a completely novel type of RF switch. A basic concept of variable ``plasma capacitors'' constructed from DC commercial fluorescent tubes has been analyzed up to 1.3 GHz. The four different configurations tested show some consistent behavior and a definite impedance change between the on and off states. A simple model reliant on RF sheath theory also shows some agreement.

  16. Evaluation of the effects of a plasma activated medium on cancer cells

    NASA Astrophysics Data System (ADS)

    Mohades, S.; Laroussi, M.; Sears, J.; Barekzi, N.; Razavi, H.

    2015-12-01

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  17. Evaluation of the effects of a plasma activated medium on cancer cells

    SciTech Connect

    Mohades, S.; Laroussi, M. Sears, J.; Barekzi, N.; Razavi, H.

    2015-12-15

    The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to a minimum essential culture medium. The activated medium is then used to treat SCaBER cancer cells. Results indicate that the plasma activated medium can kill the cancer cells in a dose dependent manner, retain its killing effect for several hours, and is as effective as apoptosis inducing drugs.

  18. Deactivation of A549 cancer cells in vitro by a dielectric barrier discharge plasma needle

    SciTech Connect

    Huang Jun; Chen Wei; Li Hui; Wang Xingquan; Lv Guohua; Wang Pengye; Khohsa, M. Latif; Guo Ming; Feng Kecheng; Yang Size

    2011-03-01

    An inactivation mechanism study on A549 cancer cells by means of a dielectric barrier discharge plasma needle is presented. The neutral red uptake assay provides a quantitative estimation of cell viability after plasma treatment. Experimental results show that the efficiency of argon plasma for the inactivation process is very dependent on power and treatment time. A 27 W power and 120 s treatment time along with 900 standard cubic centimeter per minute Ar flow and a nozzle-to-sample separation of 3 mm are the best parameters of the process. According to the argon emission spectra of the plasma jet and the optical microscope images of the A549 cells after plasma treatment, it is concluded that the reactive species (for example, OH and O) in the argon plasma play a major role in the cell deactivation.

  19. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    SciTech Connect

    Ishaq, M.; Bazaka, K.; Ostrikov, K.

    2015-12-15

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  20. Intracellular effects of atmospheric-pressure plasmas on melanoma cancer cells

    NASA Astrophysics Data System (ADS)

    Ishaq, M.; Bazaka, K.; Ostrikov, K.

    2015-12-01

    Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown as a promising tool for cancer treatment. The mechanism of the plasma action is attributed to generation of reactive oxygen and nitrogen species, electric fields, charges, and photons. The relative importance of different modes of action of atmospheric-pressure plasmas depends on the process parameters and specific treatment objects. Hence, an in-depth understanding of biological mechanisms that underpin plasma-induced death in cancer cells is required to optimise plasma processing conditions. Here, the intracellular factors involved in the observed anti-cancer activity in melanoma Mel007 cells are studied, focusing on the effect of the plasma treatment dose on the expression of tumour suppressor protein TP73. Over-expression of TP73 causes cell growth arrest and/or apoptosis, and hence can potentially be targeted to enhance killing efficacy and selectivity of the plasma treatment. It is shown that the plasma treatment induces dose-dependent up-regulation of TP73 gene expression, resulting in significantly elevated levels of TP73 RNA and protein in plasma-treated melanoma cells. Silencing of TP73 expression by means of RNA interference inhibited the anticancer effects of the plasma, similar to the effect of caspase inhibitor z-VAD or ROS scavenger N-acetyl cysteine. These results confirm the role of TP73 protein in dose-dependent regulation of anticancer activity of atmospheric-pressure plasmas.

  1. GLIAL ABNORMALITIES IN MOOD DISORDERS

    PubMed Central

    Öngür, Dost; Bechtholt, Anita J.; Carlezon, William A.; Cohen, Bruce M.

    2015-01-01

    Multiple lines of evidence indicate that mood disorders are associated with abnormalities in the brain's cellular composition, especially in glial cells. Considered inert support cells in the past, glial cells are now known to be important for brain function. Treatments for mood disorders enhance glial cell proliferation, and experimental stimulation of cell growth has antidepressant effects in animal models of mood disorders. These findings suggest that the proliferation and survival of glial cells may be important in the pathogenesis of mood disorders and may be possible targets for the development of new treatments. In this chapter, we will review the evidence for glial abnormalities in mood disorders. We will discuss glial cell biology and evidence from postmortem studies of mood disorders. This is not carry out a comprehensive review; rather we selectively discuss existing evidence in building an argument for the role of glial cells in mood disorders. PMID:25377605

  2. Frequency of cell treatment with cold microwave argon plasma is important for the final outcome

    NASA Astrophysics Data System (ADS)

    Sysolyatina, E.; Vasiliev, M.; Kurnaeva, M.; Kornienko, I.; Petrov, O.; Fortov, V.; Gintsburg, A.; Petersen, E.; Ermolaeva, S.

    2016-07-01

    The purpose of this work was to establish the influence of a regime of cold microwave argon plasma treatments on the physiological characteristics of human fibroblasts and keratinocytes. We used three regimes of plasma application: a single treatment, double treatment with a 48 h interval, and daily treatments for 3 d. Cell proliferation after plasma application was quantified in real time, and immunohistochemistry was used to establish the viability of the cells and determine changes in their physiology. It was established that the frequency of cell treatments is important for the outcome. In the samples treated with single plasma application and double plasma applications with a 48 h interval, a 42.6% and 32.0% increase was observed in the number of cells, respectively. In addition, there were no signs of deoxyribonucleic acid breaks immediately after plasma application. In contrast, plasma application increased the accumulation of cells in the active phases of the cell cycle. The activation of proliferation correlated with a decrease in the level of β-galactosidase, a senescence marker. This could be due to cell renovation after plasma application. Daily treatment decreased cell proliferation up to 29.1% in comparison with the control after 3 d.

  3. Screening rat mesenchymal stem cell attachment and differentiation on surface chemistries using plasma polymer gradients.

    PubMed

    Wang, Peng-Yuan; Clements, Lauren R; Thissen, Helmut; Tsai, Wei-Bor; Voelcker, Nicolas H

    2015-01-01

    It is well known that the surface chemistry of biomaterials is important for both initial cell attachment and the downstream cell response. Surface chemistry gradients are a new format that allows the screening of the subtleties of cell-surface interactions in high throughput. In this study, two surface chemical gradients were fabricated using diffusion control during plasma polymerization via a tilted mask. Acrylic acid (AA) plasma polymer gradients were coated on a uniform 1,7-octadiene (OD) plasma polymer layer to generate OD-AA plasma polymer gradients, whilst diethylene glycol dimethyl ether (DG) plasma polymer gradients were coated on a uniform AA plasma polymer layer to generate AA-DG plasma polymer gradients. Gradient surfaces were characterized by X-ray photoelectron spectroscopy, infrared microscopy mapping, profilometry, water contact angle (WCA) goniometry and atomic force microscopy. Cell attachment density and differentiation into osteo- and adipo-lineages of rat-bone-marrow mesenchymal stem cells (rBMSCs) was studied on gradients. Cell adhesion after 24 h culture was sensitive to the chemical gradients, resulting in a cell density gradient along the substrate. The slope of the cell density gradient changed between 24 and 6 days due to cell migration and growth. Induction of rBMSCs into osteoblast- and adipocyte-like cells on the two plasma polymer gradients suggested that osteogenic differentiation was sensitive to local cell density, but adipogenic differentiation was not. Using mixed induction medium (50% osteogenic and 50% adipogenic medium), thick AA plasma polymer coating (>40 nm thickness with ∼11% COOH component and 35° WCA) robustly supported osteogenic differentiation as determined by colony formation and calcium deposition. This study establishes a simple but powerful approach to the formation of plasma polymer based gradients, and demonstrates that MSC behavior can be influenced by small changes in surface chemistry. PMID:25246312

  4. Plasma membranes modified by plasma treatment or deposition as solid electrolytes for potential application in solid alkaline fuel cells.

    PubMed

    Reinholdt, Marc; Ilie, Alina; Roualdès, Stéphanie; Frugier, Jérémy; Schieda, Mauricio; Coutanceau, Christophe; Martemianov, Serguei; Flaud, Valérie; Beche, Eric; Durand, Jean

    2012-01-01

    In the highly competitive market of fuel cells, solid alkaline fuel cells using liquid fuel (such as cheap, non-toxic and non-valorized glycerol) and not requiring noble metal as catalyst seem quite promising. One of the main hurdles for emergence of such a technology is the development of a hydroxide-conducting membrane characterized by both high conductivity and low fuel permeability. Plasma treatments can enable to positively tune the main fuel cell membrane requirements. In this work, commercial ADP-Morgane® fluorinated polymer membranes and a new brand of cross-linked poly(aryl-ether) polymer membranes, named AMELI-32®, both containing quaternary ammonium functionalities, have been modified by argon plasma treatment or triallylamine-based plasma deposit. Under the concomitant etching/cross-linking/oxidation effects inherent to the plasma modification, transport properties (ionic exchange capacity, water uptake, ionic conductivity and fuel retention) of membranes have been improved. Consequently, using plasma modified ADP-Morgane® membrane as electrolyte in a solid alkaline fuel cell operating with glycerol as fuel has allowed increasing the maximum power density by a factor 3 when compared to the untreated membrane. PMID:24958295

  5. Plasma Membranes Modified by Plasma Treatment or Deposition as Solid Electrolytes for Potential Application in Solid Alkaline Fuel Cells

    PubMed Central

    Reinholdt, Marc; Ilie, Alina; Roualdès, Stéphanie; Frugier, Jérémy; Schieda, Mauricio; Coutanceau, Christophe; Martemianov, Serguei; Flaud, Valérie; Beche, Eric; Durand, Jean

    2012-01-01

    In the highly competitive market of fuel cells, solid alkaline fuel cells using liquid fuel (such as cheap, non-toxic and non-valorized glycerol) and not requiring noble metal as catalyst seem quite promising. One of the main hurdles for emergence of such a technology is the development of a hydroxide-conducting membrane characterized by both high conductivity and low fuel permeability. Plasma treatments can enable to positively tune the main fuel cell membrane requirements. In this work, commercial ADP-Morgane® fluorinated polymer membranes and a new brand of cross-linked poly(aryl-ether) polymer membranes, named AMELI-32®, both containing quaternary ammonium functionalities, have been modified by argon plasma treatment or triallylamine-based plasma deposit. Under the concomitant etching/cross-linking/oxidation effects inherent to the plasma modification, transport properties (ionic exchange capacity, water uptake, ionic conductivity and fuel retention) of membranes have been improved. Consequently, using plasma modified ADP-Morgane® membrane as electrolyte in a solid alkaline fuel cell operating with glycerol as fuel has allowed increasing the maximum power density by a factor 3 when compared to the untreated membrane. PMID:24958295

  6. Induction of growth arrest in colorectal cancer cells by cold plasma and gold nanoparticles

    PubMed Central

    Irani, Shiva; Shahmirani, Zhohreh; Mirpoor, Shahriar

    2015-01-01

    Introduction Guided treatments with nanoparticles and cold atmospheric plasma are a new approach in cancer therapy. Plasma is an ionized gas that has reactive and energetic particles and can be produced in the laboratory by different methods. Material and methods Plasma jet therapy was employed to irradiate HCT-116 cells (human colorectal cancer cells) which were cultured in the presence of gold nanoparticles (GNPs). Cell cytotoxicity was tested with 3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT), and cancerous cell apoptosis was shown by 4’,6-diamidino-2-phenylindole (DAPI) staining. Results The results showed that cell death was increased significantly with p < 0.001 by cold atmospheric plasma in the presence of gold nanoparticles. Conclusions It appears that non-thermal plasma and gold nanoparticles synergism is a promising approach in colon cancer therapy. PMID:26788092

  7. Specific N-glycans of Hepatocellular Carcinoma Cell Surface and the Abnormal Increase of Core-α-1, 6-fucosylated Triantennary Glycan via N-acetylglucosaminyltransferases-IVa Regulation.

    PubMed

    Nie, Huan; Liu, Xia; Zhang, Yubao; Li, Tingting; Zhan, Chao; Huo, Wenjuan; He, Anshun; Yao, Yuanfei; Jin, Yu; Qu, Youpeng; Sun, Xue-Long; Li, Yu

    2015-01-01

    Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC. PMID:26537865

  8. Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE).

    PubMed Central

    Mitamura, K; Kang, H; Tomita, Y; Hashimoto, H; Sawada, S; Horie, T

    1991-01-01

    We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE. Images Fig. 2 PMID:1893618

  9. Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium.

    PubMed

    Utsumi, Fumi; Kajiyama, Hiroaki; Nakamura, Kae; Tanaka, Hiromasa; Mizuno, Masaaki; Toyokuni, Shinnya; Hori, Masaru; Kikkawa, Fumitaka

    2016-06-01

    Non-thermal atmospheric pressure plasma has been widely studied in recent years in many fields, including cancer treatment. However, its efficiency for inducing apoptosis sometimes varies depending on the cell species and experimental conditions. The aim of this study was to elucidate what causes these differences in responses to plasma treatment. Using four ovarian cancer cell lines, the cell density had a markedly negative impact on the proliferation inhibition rate (PIR) and it was more obvious in OVCAR-3 and NOS2 cells. Furthermore, TOV21G and ES-2 cells were drastically sensitive to plasma‑activated medium (PAM) compared with the other two cell lines. We demonstrated that the proportion of reactive oxygen species and cell number had a marked impact on the effect of PAM against ovarian cancer cells. Additionally it was suggested that the morphological features of cells were also closely related to the sensitivity of cancer cells to the plasma treatment. PMID:27035127

  10. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

    PubMed Central

    Lunov, Oleg; Zablotskii, Vitalii; Churpita, Olexander; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

    2014-01-01

    Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications. PMID:25410636

  11. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

    NASA Astrophysics Data System (ADS)

    Lunov, Oleg; Zablotskii, Vitalii; Churpita, Olexander; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

    2014-11-01

    Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications.

  12. Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and p15CDKN2B genes in certain B cell non-Hodgkin's lymphomas. Functional studies in a cell line (Granta 519).

    PubMed

    Jadayel, D M; Lukas, J; Nacheva, E; Bartkova, J; Stranks, G; De Schouwer, P J; Lens, D; Bartek, J; Dyer, M J; Kruger, A R; Catovsky, D

    1997-01-01

    Abnormalities of several cell-cycle regulatory genes including cyclin D1, p16CDKN2 and p15CDKN2B have been described in B cell non-Hodgkin's lymphoma (B-NHL). We describe a new B-NHL cell line (Granta 519), with concurrent abnormalities of the cyclin D1, pl6CDKN2 and pl5CDKN2B genes. An independent clinical case of mantle cell NHL (Mc-NHL) with concomitant overexpression of cyclin D1, and deletion of the p16CDKN2 gene was also identified, suggesting that this combination of oncogenic aberration is a pathophysiologic contribution to a subset of NHL cases. More in-depth functional studies of this concept were facilitated by the availability of the cell line Granta 519 which was derived from a case of high-grade NHL and has a mature B cell immunophenotype. Cytogenetic analysis identified translocation t(11;14)(q13;q32) and complex rearrangements involving chromosomes 9p22, 13p21, 17pl1, and 18q21. Molecular analysis identified overexpression of cyclin D1 mRNA and biallelic deletion of the p16CDKN2 and p15CDKN2B genes. To elucidate the effect of these genetic abnormalities on the G1 control of Granta 519 cells, the level and function of the major components of the cyclinD/retinoblastoma (RB) pathway were investigated. Cyclin D1 was dominant among the D-type cyclins, formed abundant complexes with cyclin-dependent kinase (Cdk) Cdk4 rather than Cdk6, and the immunoprecipitated cyclin D1/Cdk4 holoenzyme was active as a pRB kinase. Electroporation of wild-type pl6CDKN2 arrested the Granta 519 cells in G1, consistent with the p16CDKN2 loss as a biologically relevant event during multistep evolution of the tumor, and with the expression of functional pRB. Direct cooperation of these distinct abnormalities to cell-cycle, deregulation in NHL cells was suggested by G1 acceleration upon inducible overexpression of cyclin D1 in a control breast cancer cell line lacking p16CDKN2, an effect which could be prevented by ectopic expression of p16CDKN2. Taken together, these data

  13. From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets.

    PubMed

    Dang, Van Duc; Hilgenberg, Ellen; Ries, Stefanie; Shen, Ping; Fillatreau, Simon

    2014-06-01

    B lymphocytes have a unique role as antibody-producing cells. Antibodies are key mediators of humoral immunity against infections, and are thought to account for the protection afforded by successful vaccines. B cells can also secrete cytokines and subsequently regulate immune responses mediated by T and innate cells. Remarkably, recent studies identified plasma blasts/plasma cells as the main types of activated B cells producing the cytokines interleukin (IL)-10, IL-35, tumor necrosis factor (TNF)-α, IL-17, and GM-CSF in various contexts in mice. Here, we discuss these observations, which suggest the existence of various subsets of plasma blast/plasma cells distinguishable through their cytokine expression pattern. PMID:24637161

  14. Cold Atmospheric Plasma Induces a Predominantly Necrotic Cell Death via the Microenvironment

    PubMed Central

    Cousty, Sarah; Cambus, Jean-Pierre; Valentin, Alexis

    2015-01-01

    Introduction Cold plasma is a partially ionized gas generated by an electric field at atmospheric pressure that was initially used in medicine for decontamination and sterilization of inert surfaces. There is currently growing interest in using cold plasma for more direct medical applications, mainly due to the possibility of tuning it to obtain selective biological effects in absence of toxicity for surrounding normal tissues,. While the therapeutic potential of cold plasma in chronic wound, blood coagulation, and cancer treatment is beginning to be documented, information on plasma/cell interaction is so far limited and controversial. Methods and Results Using normal primary human fibroblast cultures isolated from oral tissue, we sought to decipher the effects on cell behavior of a proprietary cold plasma device generating guided ionization waves carried by helium. In this model, cold plasma treatment induces a predominantly necrotic cell death. Interestingly, death is not triggered by a direct interaction of the cold plasma with cells, but rather via a transient modification in the microenvironment. We show that modification of the microenvironment redox status suppresses treatment toxicity and protects cells from death. Moreover, necrosis is not accidental and seems to be an active response to an environmental cue, as its execution can be inhibited to rescue cells. Conclusion These observations will need to be taken into account when studying in vitro plasma/cell interaction and may have implications for the design and future evaluation of the efficacy and safety of this new treatment strategy. PMID:26275141

  15. Controls to validate plasma samples for cell free DNA quantification.

    PubMed

    Pallisgaard, Niels; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund; Brandslund, Ivan; Jakobsen, Anders

    2015-06-15

    Recent research has focused on the utility of cell free DNA (cfDNA) in serum and plasma for clinical application, especially in oncology. The literature holds promise of cfDNA as a valuable tumour marker to be used for treatment selection, monitoring and follow-up. The results, however, are diverging due to methodological differences with lack of standardisation and definition of sensitivity. The new biological information has not yet come into routine use. The present study presents external standardisation by spiking with non-human DNA fragments to control for loss of DNA during sample preparation and measurement. It also suggests a method to control for admixture of DNA from normal lymphocytes by utilizing the unique immunoglobulin gene rearrangement in the B-cells. The results show that this approach improves the quality of the analysis and lowers the risk of falsely increased values. In conclusion we suggest a new method to improve the accuracy of cfDNA measurements easily incorporated in the current technology. PMID:25896958

  16. Identification of human plasma cells with a lamprey monoclonal antibody

    PubMed Central

    Yu, Cuiling; Liu, Yanling; Chan, Justin Tze Ho; Tong, Jiefei; Li, Zhihua; Shi, Mengyao; Davani, Dariush; Parsons, Marion; Khan, Srijit; Zhan, Wei; Kyu, Shuya; Grunebaum, Eyal; Campisi, Paolo; Propst, Evan J.; Jaye, David L.; Trudel, Suzanne; Moran, Michael F.; Ostrowski, Mario; Herrin, Brantley R.; Lee, F. Eun-Hyung; Sanz, Ignacio; Cooper, Max D.; Ehrhardt, Götz R.A.

    2016-01-01

    Ab-producing plasma cells (PCs) serve as key participants in countering pathogenic challenges as well as being contributors to autoimmune and malignant disorders. Thus far, only a limited number of PC–specific markers have been identified. The characterization of the unique variable lymphocyte receptor (VLR) Abs that are made by evolutionarily distant jawless vertebrates prompted us to investigate whether VLR Abs could detect novel PC antigens that have not been recognized by conventional Abs. Here, we describe a monoclonal lamprey Ab, VLRB MM3, that was raised against primary multiple myeloma cells. VLRB MM3 recognizes a unique epitope of the CD38 ectoenzyme that is present on plasmablasts and PCs from healthy individuals and on most, but not all, multiple myelomas. Binding by the VLRB MM3 Ab coincides with CD38 dimerization and NAD glycohydrolase activity. Our data demonstrate that the lamprey VLRB MM3 Ab is a unique reagent for the identification of plasmablasts and PCs, with potential applications in the diagnosis and therapeutic intervention of PC or autoimmune disorders. PMID:27152361

  17. Long and short term effects of plasma treatment on meristematic plant cells

    NASA Astrophysics Data System (ADS)

    Puač, N.; Živković, S.; Selaković, N.; Milutinović, M.; Boljević, J.; Malović, G.; Petrović, Z. Lj.

    2014-05-01

    In this paper, we will present results of plasma treatments of meristematic cells of Daucus carota. Plasma needle was used as an atmospheric pressure/gas composition source of non-equilibrium plasma in all treatments. Activity of antioxidant enzymes superoxide dismutase and catalase was measured immediately after plasma treatment and after two weeks following the treatment. Superoxide dismutase activity was increased in samples immediately after the plasma treatment. On the other hand, catalase activity was much higher in treated samples when measured two weeks after plasma treatment. These results show that there is a direct proof of the triggering of signal transduction in the cells by two reactive oxygen species H2O2 and O2-, causing enzyme activity and short and long term effects even during the growth of calli, where the information is passed to newborn cells over the period of two weeks.

  18. Impaired monocytic IL-10 production in sarcoidosis and potential link to abnormalities in iNKT cells

    PubMed Central

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

    2016-01-01

    Sarcoidosis is a multi-system granulomatous disorder characterised by marked TH1-biased T cell expansion. The cause of T cell over-activity is unknown. We hypothesized that a cellular source for IL-10 might be defective, resulting in loss of regulation of T cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from blood of corticosteroid-naïve sarcoidosis patients (n=51) produced less IL-10 compared to controls, and were less able to suppress T cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity. We then questioned if defects in iNKT cells (known to be reduced in sarcoidosis), might be responsible for this reduced IL-10 production since iNKT cells can interact with monocytes. We found that monocytic IL-10 production were higher where there were greater numbers of circulating iNKT cells. In vitro, iNKT cells enhanced monocytic IL-10 production. Defective IL-10 production and T cell suppression by sarcoidosis monocytes can be restored by co-culture with iNKT cells, in a CD1d-requiring and contact-dependent process. We suggest that reduced iNKT cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T cell expansion in sarcoidosis. The findings provide fresh insight into sarcoidosis disease mechanism, and interaction between iNKT cells and monocytes. PMID:24723379

  19. Comparing plasma and X-ray exposure and identifying vulnerable cell parts

    NASA Astrophysics Data System (ADS)

    Graham, Bill

    2012-10-01

    Here two issues in plasma medicine that are being addressed in a collaboration between the Centre of Plasma Physics and the School of Pharmacy at Queen's University Belfast and the Plasma Institute at York University UK will be discussed. Recent measurements of the interaction of plasmas created directly in DMEM cell medium and MDAMB-231, a human breast cancer cell line, showed evidence of reduced cell viability and of DNA damage. The same set of experiments were undertaken but with X-ray exposure. A correlation of the dependence on plasma exposure time and X-ray dose was observed which might point the way to dose definition in plasma medicine. We have also been working to identify the cell parts most vulnerable to plasma exposure. In this study a 10 kHz atmospheric pressure non-thermal plasma jet, operating in He/0.5%O2 and characterized to determine the behavior of many of the plasma species, was incident onto the surface of media containing either bacterial strains, in their planktonic and biofilm forms, or isolated bacterial plasmid DNA. The results of measurements to look for changes in plasmid structural conformation, rates of single and double strand breaks, the catalytic activity of certain bacterial enzymes, the peroxidation of lipid content of the bacterial cells, the leakage of ATP and Scanning Electron Microscope (SEM) images will be discussed.

  20. Impact of non-thermal plasma treatment on MAPK signaling pathways of human immune cell lines.

    PubMed

    Bundscherer, Lena; Wende, Kristian; Ottmüller, Katja; Barton, Annemarie; Schmidt, Anke; Bekeschus, Sander; Hasse, Sybille; Weltmann, Klaus-Dieter; Masur, Kai; Lindequist, Ulrike

    2013-10-01

    In the field of wound healing research non-thermal plasma (NTP) increasingly draws attention. Next to its intensely studied antibacterial effects, some studies already showed stimulating effects on eukaryotic cells. This promises a unique potential in healing of chronic wounds, where effective therapies are urgently needed. Immune cells do play an important part in the process of wound healing and their reaction to NTP treatment has yet been rarely examined. Here, we studied the impact of NTP treatment using the kinpen on apoptotic and proliferative cell signaling pathways of two human immune cell lines, the CD4(+)T helper cell line Jurkat and the monocyte cell line THP-1. Depending on NTP treatment time the number of apoptotic cells increased in both investigated cell types according to a caspase 3 assay. Western blot analysis pointed out that plasma treatment activated pro-apoptotic signaling proteins like p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase 1 and 2 (JNK 1/2) in both cell types. Stronger signals were detected in Jurkat cells at comparable plasma treatment times. Intriguingly, exposure of Jurkat and THP-1 cells to plasma also activated the pro-proliferative signaling molecules extracellular signal-regulated kinase 1/2 (ERK 1/2) and MAPK/ERK kinase 1 and 2 (MEK 1/2). In contrast to Jurkat cells, the anti-apoptotic heat shock protein 27 (HSP27) was activated in THP-1 cells after plasma treatment, indicating a possible mechanism how THP-1 cells may reduce programmed cell death. In conclusion, several signaling cascades were activated in the examined immune cell lines after NTP treatment and in THP-1 monocytes a possible defense mechanism against plasma impacts could be revealed. Therefore, plasma might be a treatment option for wound healing. PMID:23735483

  1. Developmental Outcome and Related Abnormalities in Goats: Comparison Between Somatic Cell Nuclear Transfer- and In Vivo-Derived Concepti During Pregnancy Through Term.

    PubMed

    Martins, Leonardo Tondello; Neto, Saul Gaudêncio; Tavares, Kaio César Simiano; Calderón, Carlos Enrique Méndez; Aguiar, Luis Henrique; Lazzarotto, Cícera Regina; Ongaratto, Felipe Ledur; Rodrigues, Victor Hugo Vieira; Carneiro, Igor de Sá; Rossetto, Rafael; Almeida, Anderson Pinto; Fernandes, César Carneiro Linhares; Rondina, Davide; Dias, Ana Christina Oliveira; Chies, Jocelei Maria; Polejaeva, Irina A; Rodrigues, José Luiz; Forell, Fabiana; Bertolini, Luciana Relly; Bertolini, Marcelo

    2016-08-01

    Cloning by somatic cell nuclear transfer (SCNT) is characterized by low efficiency and the occurrence of developmental abnormalities, which are rather poorly studied phenomena in goats. This study aimed at comparing overall SCNT efficiency in goats by using in vitro-matured (IVM) or in vivo-matured oocytes and fibroblast donor cells (mock transfected, transgenic, or wild type), also characterizing symptoms of the Abnormal Offspring Syndrome (AOS) in development, comparing results with pregnancies produced by artificial insemination (AI) and in vivo-derived (IVD) embryos. The SCNT group had lower pregnancy rate (18.3%, 11/60), total number of concepti (20.0%, 12/60), term births (3.3%, 2/60), and live births (1.7%, 1/60) than both the IVD (77.8%, 7/9; 155.5%, 14/9; 122.2%, 11/9; 88.8%, 8/9) and the AI (71.4%, 10/14; 121.4%, 17/14; 100%, 14/14; 78.5%, 11/14) groups, respectively (p < 0.05). No SCNT pregnancies reached term using IVM oocytes, but in vivo-matured oocytes resulted in two term transgenic cloned kids. The proportion fetal membrane (FM) weight/birth weight reflected an increase in FM size and cotyledonary enlargement in clones, for disproportionally bigger newborns in relation to cotyledonary numbers. Overall, goat cloning showed losses and abnormality patterns similar to the AOS in cloned cattle and sheep, which have not been previously well recognized in goats. PMID:27362734

  2. Variable susceptibility of ovarian cancer cells to non-thermal plasma-activated medium

    PubMed Central

    UTSUMI, FUMI; KAJIYAMA, HIROAKI; NAKAMURA, KAE; TANAKA, HIROMASA; MIZUNO, MASAAKI; TOYOKUNI, SHINNYA; HORI, MASARU; KIKKAWA, FUMITAKA

    2016-01-01

    Non-thermal atmospheric pressure plasma has been widely studied in recent years in many fields, including cancer treatment. However, its efficiency for inducing apoptosis sometimes varies depending on the cell species and experimental conditions. The aim of this study was to elucidate what causes these differences in responses to plasma treatment. Using four ovarian cancer cell lines, the cell density had a markedly negative impact on the proliferation inhibition rate (PIR) and it was more obvious in OVCAR-3 and NOS2 cells. Furthermore, TOV21G and ES-2 cells were drastically sensitive to plasma-activated medium (PAM) compared with the other two cell lines. We demonstrated that the proportion of reactive oxygen species and cell number had a marked impact on the effect of PAM against ovarian cancer cells. Additionally it was suggested that the morphological features of cells were also closely related PMID:27035127

  3. Anaplastic plasmacytomas: relationships to normal memory B cells and plasma cell neoplasms of immunodeficient and autoimmune mice.

    PubMed

    Qi, Chen-Feng; Shin, Dong-Mi; Li, Zhaoyang; Wang, Hongsheng; Feng, Jianxum; Hartley, Janet W; Fredrickson, Torgny N; Kovalchuk, Alexander L; Morse, Herbert C

    2010-05-01

    Anaplastic plasmacytomas (APCTs) from NFS.V(+) congenic mice and pristane-induced plasmacytic PCTs from BALB/c mice were previously shown to be histologically and molecularly distinct subsets of plasma cell neoplasms (PCNs). Here we extended these comparisons, contrasting primary APCTs and PCTs by gene expression profiling in relation to the expression profiles of normal naïve, germinal centre, and memory B cells and plasma cells. We also sequenced immunoglobulin genes from APCT and APCT-derived cell lines and defined surface phenotypes and chromosomal features of the cell lines by flow cytometry and by spectral karyotyping and fluorescence in situ hybridization. The results indicate that APCTs share many features with normal memory cells and the plasma cell-related neoplasms (PLs) of FASL-deficient mice, suggesting that APCTs and PLs are related and that both derive from memory B cells. Published in 2010 by John Wiley & Sons, Ltd. PMID:20217872

  4. Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

    PubMed Central

    Caligaris-Cappio, F; Bergui, L; Tesio, L; Pizzolo, G; Malavasi, F; Chilosi, M; Campana, D; van Camp, B; Janossy, G

    1985-01-01

    Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells. Images PMID:2931452

  5. The effects of cold atmospheric plasma on cell adhesion, differentiation, migration, apoptosis and drug sensitivity of multiple myeloma.

    PubMed

    Xu, Dehui; Luo, Xiaohui; Xu, Yujing; Cui, Qingjie; Yang, Yanjie; Liu, Dingxin; Chen, Hailan; Kong, Michael G

    2016-05-13

    Cold atmospheric plasma was shown to induce cell apoptosis in numerous tumor cells. Recently, some other biological effects, such as induction of membrane permeation and suppression of migration, were discovered by plasma treatment in some types of tumor cells. In this study, we investigated the biological effects of plasma treatment on multiple myeloma cells. We detected the detachment of adherent myeloma cells by plasma, and the detachment area was correlated with higher density of hydroxyl radical in the gas phase of the plasma. Meanwhile, plasma could promote myeloma differentiation by up-regulating Blimp-1 and XBP-1 expression. The migration ability was suppressed by plasma treatment through decreasing of MMP-2 and MMP-9 secretion. In addition, plasma could increase bortezomib sensitivity and induce myeloma cell apoptosis. Taking together, combination with plasma treatment may enhance current chemotherapy and probably improve the outcomes. PMID:27067049

  6. Evaluation of the Efficacy of the Plasma Pencil Against Cancer Cells

    NASA Astrophysics Data System (ADS)

    Mohades, Soheila; Barekzi, Nazir; Razavi, Hamid; Laroussi, Mounir

    2014-10-01

    The plasma pencil generates low temperature and atmospheric pressure plasma. To generate the plasma, high voltage pulses with short width (from nanosecond to microsecond) are applied to a noble gas. The working gas can be helium, argon or a mixture of these with air or oxygen. Generating plasma with helium provides a tolerable temperature for biological cells and tissues. Diagnostic measurements on the plasma plume has revealed the presence of active agents such as reactive oxygen species (ROS) and nitrogen reactive species (RNS), which are known to have biological implications. Recently, low temperature plasma has drawn attention to its potential in cancer therapy. In our lab, the plasma pencil has been used to treat leukemia, prostate and epithelial cancer cells. The cancer cell line used here is the SCaBER (ATCC®HTB3™) cell line originating from a human bladder cancer. The results indicate that specific species induce the molecular mechanisms associated with cell death. The death of cells after plasma treatment will be studied using assays, such as DNA laddering and Caspase-3 activation, to elucidate the mechanism of the apoptotic or necrotic pathways.

  7. Pharmacological screening of bryophyte extracts that inhibit growth and induce abnormal phenotypes in human HeLa cancer cells.

    PubMed

    Krzaczkowski, Lucie; Wright, Michel; Rebérioux, Delphine; Massiot, Georges; Etiévant, Chantal; Gairin, Jean Edouard

    2009-08-01

    Antitumor activities of substances from natural sources apart from vascular plants and micro-organisms have been poorly investigated. Here we report on a pharmacological screening of a bryophyte extract library using a phenotypic cell-based assay revealing microtubules, centrosomes and DNA. Among the 219 moss extracts tested, we identified 41 extracts acting on cell division with various combinations of significant effects on interphasic and mitotic cells. Seven extracts were further studied using a cell viability assay, cell cycle analysis and the phenotypic assay. Three distinct pharmacological patterns were identified including two unusual phenotypes. PMID:19709324

  8. Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury☆

    PubMed Central

    Ye, Fagang; Li, Haiyan; Qiao, Guangxi; Chen, Feng; Tao, Hao; Ji, Aiyu; Hu, Yanling

    2012-01-01

    Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-rich plasma and Schwann cell-like cells were mixed in suspension at a density of 1 × 106 cells/mL, prior to introduction into a poly (lactic-co-glycolic acid) conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects (platelet-rich plasma group). Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves (fibrin group). Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote peripheral nerve regeneration. PMID:25538751

  9. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    NASA Astrophysics Data System (ADS)

    Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  10. Rapid preparation of plasma membranes from avian lymphoid cells and fibroblasts for virus binding studies.

    PubMed

    Nieper, H; Müller, H

    1998-06-01

    A simple and rapid protocol for the preparation of plasma membranes from chicken embryo fibroblasts and chicken lymphoid cells was developed. Characterization of the preparations by morphological, biochemical and serological methods indicated the specific enrichment of the plasma membranes as well as cell surface proteins. Binding of infectious bursal disease virus (IBDV) particles was demonstrated after immobilization of the plasma membranes, and cell type-specific differences were observed. Although the results of these studies reflect the interaction between IBDV and isolated cells only partially, the advantages of these plasma membrane preparations, the specific enrichment of cell surface proteins, their constant quality and the possibility to store aliquots over several months, make them a useful tool for virus binding studies with avian cells. PMID:9694323

  11. Studies of micronuclei and other nuclear abnormalities in red blood cells of Colossoma macropomum exposed to methylmercury

    PubMed Central

    da Rocha, Carlos Alberto Machado; da Cunha, Lorena Araújo; da Silva Pinheiro, Raul Henrique; de Oliveira Bahia, Marcelo; Burbano, Rommel Mario Rodríguez

    2011-01-01

    The frequencies of micronuclei (MN) and morphological nuclear abnormalities (NA) in erythrocytes in the peripheral blood of tambaqui (Colossoma macropomum), treated with 2 mg.L−1 methylmercury (MeHg), were analyzed. Two groups (nine specimens in each) were exposed to MeHg for different periods (group A - 24 h; group B - 120 h). A third group served as negative control (group C, untreated; n = 9). Although, when compared to the control group there were no significant differences in MN frequency in the treated groups, for NA, the differences between the frequencies of group B (treated for 120 h) and the control group were extremely significant (p < 0.02), thus demonstrating the potentially adverse effects of MeHg on C. macropomum erythrocytes after prolonged exposure. PMID:22215976

  12. Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia

    PubMed Central

    Hyacinth, Hyacinth I.; Gee, Beatrice E.; Adamkiewicz, Thomas V.; Adams, Robert J.; Kutlar, Abdullah; Stiles, Jonathan K.; Hibbert, Jacqueline M.

    2012-01-01

    Sickle cell anemia (SCA) associated cerebrovascular disease includes vascular remodeling, abnormal cerebral blood flow (CBF) and infarction. We studied the relationships between plasma brain derived neurotropic factor (BDNF), platelet derived growth factors (PDGF-AA and -AB/BB) and high trans-cranial Doppler (TCD) velocity, an indication of CBF velocity. Baseline plasma samples from 39 children (19 SCA with abnormal/high TCD [SATCD], 13 SCA with normal TCD [SNTCD] and 7 healthy non-SCA), were assayed for BDNF, PDGF-AA and – AB/BB plus 11 other cytokines. The sensitivity, specificity and usefulness of these biomarkers for prediction of stroke incidence was investigated. All subject groups were of similar age and gender distribution. Mean BDNF was significantly higher among SATCD than SNTCD (p=0.004) as was mean PDGF-AA (p=0.001). Similarly, mean PDGF-AA was higher among SCA subjects who developed stroke than for those who did not (p=0.012). Elevated BDNF and PDGF-AA were both associated with severity of anemia. Elevated BDNF and PDGF-AA were good predictors of the presence of abnormally high CBF velocity, and PDGF-AA predicted stroke development. Stroke incidence and high TCD velocity were associated with elevated BDNF and PDGF-AA. These findings suggest a role for BDNF and PDGF-AA in the patho-physiological mechanism of cerebrovascular disease in SCA. PMID:22704695

  13. The effects of non-thermal plasmas on selected mammalian cells

    NASA Astrophysics Data System (ADS)

    Leduc, Mathieu

    Non-thermal plasma surface modifications have become indispensable processing steps in various industry and research sectors. Applications range from semiconductor processing to biotechnology and recently, plasma medicine. Non-thermal plasma sources have the advantage that a number of electron-driven chemical reactions can be produced while maintaining the gas (heavy species) temperature low, thus enabling the treatment of temperature-sensitive surfaces such as polymers, tissues and live cells. In the fields of biology and medicine, non-thermal plasmas have been primarily used for the deposition or modification of biocompatible polymers and for sterilization. Recently, non-thermal plasmas have been used to treat tissues and cells. A new field of research has emerged, Plasma Medicine, which studies the effects of non-thermal plasmas on cells and tissues for clinical applications. The Atmospheric Pressure Glow Discharge torch (APGD-t), a non-thermal plasma source, built in our laboratory was used to study the effects of non-thermal plasmas on mammalian cells. In its first application, we indirectly used the APGD-t to deposit a plasma-polymer on a glass surface and studied its effects on cultured cells. It was shown that the cells grew preferentially on the plasma-polymer, and their proliferation rate increased. The second application of the APGD-t was to further investigate previous observations of cell permeabilization obtained by plasma treatments and to apply non-thermal plasmas to cell transfection. It was demonstrated that the APGD-t is able to locally transfect adherent cells. We estimated the diameter of the pores created to be below 10 nm and that the pores remain open for less than 5 seconds. However, while investigating the mechanisms involved in cell transfection we observed that the use of higher gas flows in the negative controls (using the APGD-t but with the plasma turned off) also resulted in cell transfection. To further study this phenomena, we

  14. Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

    PubMed

    Hudecek, Michael; Bartsch, Kristina; Jäkel, Nadja; Heyn, Simone; Pfannes, Roald; Al-Ali, Haifa Kathrin; Cross, Michael; Pönisch, Wolfram; Gerecke, Ulrich; Edelmann, Jeanett; Ittel, Thomas; Niederwieser, Dietger

    2008-01-01

    A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT. PMID:18367831

  15. Abnormal Changes of Brain Cortical Anatomy and the Association with Plasma MicroRNA107 Level in Amnestic Mild Cognitive Impairment

    PubMed Central

    Wang, Tao; Shi, Feng; Jin, Yan; Jiang, Weixiong; Shen, Dinggang; Xiao, Shifu

    2016-01-01

    MicroRNA107 (Mir107) has been thought to relate to the brain structure phenotype of Alzheimer’s disease. In this study, we evaluated the cortical anatomy in amnestic mild cognitive impairment (aMCI) and the relation between cortical anatomy and plasma levels of Mir107 and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Twenty aMCI (20 aMCI) and 24 cognitively normal control (NC) subjects were recruited, and T1-weighted MR images were acquired. Cortical anatomical measurements, including cortical thickness (CT), surface area (SA), and local gyrification index (LGI), were assessed. Quantitative RT-PCR was used to examine plasma expression of Mir107, BACE1 mRNA. Thinner cortex was found in aMCI in areas associated with episodic memory and language, but with thicker cortex in other areas. SA decreased in aMCI in the areas associated with working memory and emotion. LGI showed a significant reduction in aMCI in the areas involved in language function. Changes in Mir107 and BACE1 messenger RNA plasma expression were correlated with changes in CT and SA. We found alterations in key left brain regions associated with memory, language, and emotion in aMCI that were significantly correlated with plasma expression of Mir107 and BACE1 mRNA. This combination study of brain anatomical alterations and gene information may shed lights on our understanding of the pathology of AD. Clinical Trial Registration: http://www.ClinicalTrials.gov, identifier NCT01819545. PMID:27242521

  16. Localized Patch Clamping of Plasma Membrane of a Polarized Plant Cell 1

    PubMed Central

    Taylor, Alison R.; Brownlee, Colin

    1992-01-01

    We used an ultraviolet laser to rupture a small region of cell wall of a polarized Fucus spiralis rhizoid cell and gained localized access to the plasma membrane at the growing apex. Careful control of cell turgor enabled a small portion of plasma membrane-bound cytoplasm to be exposed. Gigaohm seals allowing single-channel recordings were obtained with a high success rate using this method with conventional patch clamp techniques. ImagesFigure 1 PMID:16669092

  17. Distinct effects of TRAIL on the mitochondrial network in human cancer cells and normal cells: role of plasma membrane depolarization

    PubMed Central

    Suzuki-Karasaki, Yoshihiro; Fujiwara, Kyoko; Saito, Kosuke; Suzuki-Karasaki, Miki; Ochiai, Toyoko; Soma, Masayoshi

    2015-01-01

    Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a promising anticancer drug due to its tumor-selective cytotoxicity. Here we report that TRAIL exhibits distinct effects on the mitochondrial networks in malignant cells and normal cells. Live-cell imaging revealed that multiple human cancer cell lines and normal cells exhibited two different modes of mitochondrial responses in response to TRAIL and death receptor agonists. Mitochondria within tumor cells became fragmented into punctate and clustered in response to toxic stimuli. The mitochondrial fragmentation was observed at 4 h, then became more pronounced over time, and associated with apoptotic cell death. In contrast, mitochondria within normal cells such as melanocytes and fibroblasts became only modestly truncated, even when they were treated with toxic stimuli. Although TRAIL activated dynamin-related protein 1 (Drp1)-dependent mitochondrial fission, inhibition of this process by Drp1 knockdown or with the Drp1 inhibitor mdivi-1, potentiated TRAIL-induced apoptosis, mitochondrial fragmentation, and clustering. Moreover, mitochondrial reactive oxygen species (ROS)-mediated depolarization accelerated mitochondrial network abnormalities in tumor cells, but not in normal cells, and TRAIL caused higher levels of mitochondrial ROS accumulation and depolarization in malignant cells than in normal cells. Our findings suggest that tumor cells are more prone than normal cells to oxidative stress and depolarization, thereby being more vulnerable to mitochondrial network abnormalities and that this vulnerability may be relevant to the tumor-targeting killing by TRAIL. PMID:26057632

  18. Normal and neoplastic plasma cell membrane phenotype: studies with new monoclonal antibodies.

    PubMed Central

    Tazzari, P L; Gobbi, M; Dinota, A; Bontadini, A; Grassi, G; Cerato, C; Cavo, M; Pileri, S; Caligaris-Cappio, F; Tura, S

    1987-01-01

    Three monoclonal antibodies (MoAb), named 8A, 8F6 and 62B1, reacting with plasma cell-associated antigens, were characterized. 8A was found to be positive throughout the B cell lineage maturation steps from the immature B-committed CD10+ cell to the plasma cells. 8F6 and 62B1 reactivity is restricted to more mature cells and related lymphoid malignancies. In particular 62B1 appears to be limited to hairy cells and plasma cells. The results show that it is possible to obtain reagents reacting with plasma cells by immunizing mice with cells derived from human multiple myelomas. Furthermore, the obtained results suggest that it is possible to elicit antibodies against antigens which are present throughout all the differentiation steps of the B cell lineage. These new MoAb could help in elucidating the phenotype of the plasma cells and the relationships of multiple myelomas with other B cell proliferative disorders. Images Fig. 1 PMID:3319299

  19. Abnormal patterns of equine leucocyte differentiation antigen expression in severe combined immunodeficiency foals suggests the phenotype of normal equine natural killer cells.

    PubMed Central

    Lunn, D P; McClure, J T; Schobert, C S; Holmes, M A

    1995-01-01

    Severe combined immunodeficiency (SCID) is a fatal autosommal disease of Arabian horses that leads to failure of maturation of T- and B-lymphocyte populations, although natural killer (NK) cells are unaffected. Thymic and lymph node tissues from two foals suffering from SCID were examined in an immunohistological study using a panel of monoclonal antibodies recognising equine leucocyte differentiation antigens. In both foals, the majority of cells in lymphoid tissues had an EqCD3-EqCD4-EqCD8+ phenotype, although rare EqCD3+ cells were also detected. The EqCD3-EqCD4-EqCD8+ cells may represent an abnormal lymphocyte differentiation product resulting from the SCID defect, or alternatively may be a normal equine NK cell population. We suggest that the evidence favours the latter proposal, and that equine NK cells in normal horses therefore may be identified by an EqCD3-EqCD8+ phenotype. The implications for the nature of the equine SCID defect are discussed. Images Figure 1 PMID:7751035

  20. Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae.

    PubMed

    Kono, Keiko; Al-Zain, Amr; Schroeder, Lea; Nakanishi, Makoto; Ikui, Amy E

    2016-06-21

    Cellular wound healing or the repair of plasma membrane/cell wall damage (plasma membrane damage) occurs frequently in nature. Although various cellular perturbations, such as DNA damage, spindle misalignment, and impaired daughter cell formation, are monitored by cell cycle checkpoint mechanisms in budding yeast, whether plasma membrane damage is monitored by any of these checkpoints remains to be addressed. Here, we define the mechanism by which cells sense membrane damage and inhibit DNA replication. We found that the inhibition of DNA replication upon plasma membrane damage requires GSK3/Mck1-dependent degradation of Cdc6, a component of the prereplicative complex. Furthermore, the CDK inhibitor Sic1 is stabilized in response to plasma membrane damage, leading to cell integrity maintenance in parallel with the Mck1-Cdc6 pathway. Cells defective in both Cdc6 degradation and Sic1 stabilization failed to grow in the presence of plasma membrane damage. Taking these data together, we propose that plasma membrane damage triggers G1 arrest via Cdc6 degradation and Sic1 stabilization to promote the cellular wound healing process. PMID:27274080

  1. Plasma treatment of biomaterials to direct the differentiation of embryonic stem cells

    NASA Astrophysics Data System (ADS)

    Hanley, Erik

    In this work, we explore how embryonic stem (ES) cell differentiation patterns are affected by surface interactions with plasma-processed materials. We hypothesize that mouse embryonic stem-cell exposure to certain plasma-polymerized tetraglyme surfaces will direct their differentiation into endothelial cells. R1 mouse embryonic stem (ES) cells were plated on surfaces onto which tetraglyme was deposited by plasma polymerization. In addition, tissue-treated polystyrene and control glass cover slips were also examined. Some samples were fixed three days after plating and immunofluorescence stained with platelet endothelial-cell adhesion molecule, while the others were fixed seven days after plating and immunofluorescence stained with von Willebrand Factor. Positive results seen by ES cell derivatives precociously expressing the vWF and PECAM genetic markers on the plasma-polymerized tetraglyme treated surfaces suggest that the plasma-polymerized surfaces direct differentiation of ES cells into endothelial cells. Research goals of this dissertation include: characterization of the material properties of the plasma-polymerized tetraglyme surfaces that induce directed differentiation of ES cells into endothelial cells, optimization of the plasma-polymerization process to maximize the number of endothelial cells derived from R1 ES cells, and biological experimentation to characterize properties of the mechanism of directed differentiation. A potential application of this work is in the design and construction of an artificial blood vessel. Current small-scale arterial substitutes have proved inadequate because of thrombogenicity and infection. Moreover, the lower blood flow velocities of smaller vessels pose a different set of design criteria and introduce new problems not encountered in large arterial substitutes. By utilizing a tissue engineering approach that incorporates embryonic stem cell-derived endothelial cells, the longevity of the prosthesis can be ensured.

  2. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    PubMed

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth

  3. Appearance of peripheral blood plasma cells and memory B cells in a primary and secondary immune response in humans

    PubMed Central

    Pulickal, Anoop S.; Jol-van der Zijde, Cornelia M.; Snape, Matthew D.; Pollard, Andrew J.

    2009-01-01

    In humans, the kinetics of the appearance of memory B cells and plasma cells during primary immunization are not well defined. In this study, we assessed the primary B-cell response of rabies-antigen naive volunteers during a 3-dose course of rabies vaccine compared with the B-cell response to a booster dose of rabies vaccine given to previously immunized volunteers. After a single dose of vaccine, in the naive group plasma and memory B cells appeared later (peak at day 10) than in the primed group (peak at day 7) and were at lower frequency. The most rapid responses (day 4) were detected after a third immunization in the naive group. This is the first study to document the detailed kinetics of the plasma cell and memory B-cell responses to immunization in adult humans and to demonstrate differences in the responses that relate to the preexisting immune status of the persons. PMID:19843885

  4. The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development

    PubMed Central

    Lin, Wai W.; Yi, Zuoan; Stunz, Laura L.; Maine, Christian J.; Sherman, Linda A.; Bishop, Gail A.

    2016-01-01

    Tumor necrosis factor receptor–associated factor 3 (TRAF3) is an adaptor protein that inhibits signaling by CD40 and by the receptor for B cell–activating factor (BAFF) and negatively regulates homeostatic B cell survival. Loss-of-function mutations in TRAF3 are associated with human B cell malignancies, in particular multiple myeloma. The cytokine interleukin-6 (IL-6) supports the differentiation and survival of normal and neoplastic plasma cells. We found that mice with a deficiency in TRAF3 specifically in B cells (B-Traf3−/− mice) had about twice as many plasma cells as did their littermate controls. TRAF3-deficient B cells had enhanced responsiveness to IL-6, and genetic loss of IL-6 in B-Traf3−/− mice restored their plasma cell numbers to normal. TRAF3 inhibited IL-6 receptor (IL-6R)–mediated signaling by facilitating the association of PTPN22 (a nonreceptor protein tyrosine phosphatase) with the kinase Janus-activated kinase 1 (Jak1), which in turn blocked phosphorylation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Consistent with these results, the number of plasma cells in the PTPN22-deficient mice was increased compared to that in the wild-type mice. Our findings identify TRAF3 and PTPN22 as inhibitors of IL-6R signaling in B cells and reveal a previously uncharacterized role for TRAF3 in the regulation of plasma cell differentiation. PMID:26329582

  5. Elisidepsin Interacts Directly with Glycosylceramides in the Plasma Membrane of Tumor Cells to Induce Necrotic Cell Death

    PubMed Central

    Molina-Guijarro, José Manuel; García, Carolina; Macías, Álvaro; García-Fernández, Luis Francisco; Moreno, Cristina; Reyes, Fernando; Martínez-Leal, Juan Fernando; Fernández, Rogelio; Martínez, Valentín; Valenzuela, Carmen; Lillo, M. Pilar; Galmarini, Carlos M.

    2015-01-01

    Plasma membrane integrity is essential for cell life. Any major break on it immediately induces the death of the affected cell. Different molecules were described as disrupting this cell structure and thus showing antitumor activity. We have previously defined that elisidepsin (Irvalec®, PM02734) inserts and self-organizes in the plasma membrane of tumor cells, inducing a rapid loss of membrane integrity, cell permeabilization and necrotic death. Here we show that, in sensitive HCT-116 colorectal cells, all these effects are consequence of the interaction of elisidepsin with glycosylceramides in the cell membrane. Of note, an elisidepsin-resistant subline (HCT-116-Irv) presented reduced levels of glycosylceramides and no accumulation of elisidepsin in the plasma membrane. Consequently, drug treatment did not induce the characteristic necrotic cell death. Furthermore, GM95, a mutant derivative from B16 mouse melanoma cells lacking ceramide glucosyltransferase (UGCG) activity and thus the synthesis of glycosylceramides, was also resistant to elisidepsin. Over-expression of UGCG gene in these deficient cells restored glycosylceramides synthesis, rendering them sensitive to elisidepsin, at a similar level than parental B16 cells. These results indicate that glycosylceramides act as membrane targets of elisidepsin, facilitating its insertion in the plasma membrane and the subsequent membrane permeabilization that leads to drug-induced cell death. They also indicate that cell membrane lipids are a plausible target for antineoplastic therapy. PMID:26474061

  6. Plasma cell neoplasms in US solid organ transplant recipients.

    PubMed

    Engels, Eric A; Clarke, Christina A; Pfeiffer, Ruth M; Lynch, Charles F; Weisenburger, Dennis D; Gibson, Todd M; Landgren, Ola; Morton, Lindsay M

    2013-06-01

    Transplant recipients have elevated risk for plasma cell neoplasms (PCNs, comprising multiple myeloma and plasmacytoma), but little is known about risk factors in the transplant setting. Through linkage of the US solid organ transplant registry with 15 state/regional cancer registries, we identified 140 PCNs in 202 600 recipients (1987-2009). PCN risk was 1.8-fold increased relative to the general population (standardized incidence ratio [SIR] 1.80, 95%CI 1.51-2.12). Among cases, 102 were multiple myeloma (SIR 1.41) and 38 were plasmacytoma (SIR 7.06). PCN incidence increased with age, but due to the rarity of PCNs in younger people in the general population, SIRs were highest in younger transplant recipients (p = 0.03). PCN risk was especially high in recipients who were Epstein-Barr virus (EBV) seronegative at transplantation (SIR 3.93). EBV status was known for 18 tumors, of which 7 (39%) were EBV positive. Following liver transplantation, PCN risk was higher in recipients with cholestatic liver disease (SIR 2.78); five of these cases had primary biliary cirrhosis (PBC). A role for primary EBV infection after transplantation is supported by the increased PCN risk in young EBV seronegative recipients and the presence of EBV in tumors. PBC may be another risk factor, perhaps by causing chronic immune activation. PMID:23635036

  7. Quantification of Clonal Circulating Plasma cells in Relapsed Multiple Myeloma

    PubMed Central

    Gonsalves, Wilson I; Morice, William G; Rajkumar, S. Vincent; Gupta, Vinay; Timm, Michael M; Dispenzieri, Angela; Buadi, Francis K; Lacy, Martha Q; Singh, Preet P; Kapoor, Prashant; Gertz, Morie A; Kumar, Shaji K

    2014-01-01

    The presence of clonal circulating plasma cells (cPCs) remains a marker of high-risk disease in newly diagnosed multiple myeloma (MM) patients. However, its prognostic utility in MM patients with previously treated disease is unknown. We studied 647 consecutive patients with previously treated MM seen at the Mayo Clinic, Rochester who had their peripheral blood evaluated for cPCs by multi-parameter flow cytometry. Of these patients, 145 had actively relapsing disease while the remaining 502 had disease that was in a plateau and included 68 patients in complete remission (CR) and 434 patients with stable disease. Patients with actively relapsing disease were more likely to have clonal cPCs than those in a plateau (P < 0.001). None of the patients in CR had any clonal cPCs detected. Among patients whose disease was in a plateau, the presence of clonal cPCs predicted for a worse median survival (22 months vs. not reached; P=0.004). Among actively relapsing patients, the presence of ≥100 cPCs predicted for a worse survival after flow cytometry analysis (12 months vs. 33 months; P<0.001). Future studies are needed to determine the role of these findings in developing a risk-adapted treatment approach in MM patients with actively relapsing disease. PMID:25113422

  8. Improvement of early cell adhesion on Thai silk fibroin surface by low energy plasma.

    PubMed

    Amornsudthiwat, Phakdee; Mongkolnavin, Rattachat; Kanokpanont, Sorada; Panpranot, Joongjai; Wong, Chiow San; Damrongsakkul, Siriporn

    2013-11-01

    Low energy plasma has been introduced to treat the surface of Thai silk fibroin which should be enhanced for cell adhesion due to its native hydrophobic surface. Plasma surface treatment could introduce desirable hydrophilic functionalities on the surface without using any chemicals. In this work, nitrogen glow discharge plasma was generated by a low energy AC50Hz power supply system. The plasma operating conditions were optimized to reach the highest nitrogen active species by using optical emission spectroscopy. X-ray photoelectron spectroscopy (XPS) revealed that amine, hydroxyl, ether, and carboxyl groups were induced on Thai silk fibroin surface after plasma treatment. The results on Fourier transform infrared attenuated total reflection (FTIR-ATR) spectroscopy confirmed that the plasma treated effects were only on the outermost layer since there was no change in the bulk chemistry. The surface topography was insignificantly changed from the detection with atomic force microscopy (AFM). The plasma-treated effects were the improved surface wettability and cell adhesion. After a 90-s treatment, the water contact angle was at 20°, while the untreated surface was at 70°. The early cell adhesion of L929 mouse fibroblast was accelerated. L929 cells only took 3h to reach 100% cell adhesion on 90 s N2 plasma-treated surface, while there was less than 50% cell adhesion on the untreated Thai silk fibroin surface after 6h of culture. The cell adhesion results were in agreement with the cytoskeleton development. L929 F-actin was more evident on 90 s N2 plasma-treated surface than others. It could be concluded that a lower energy AC50Hz plasma system enhanced early L929 mouse fibroblast adhesion on Thai silk fibroin surface without any significant change in surface topography and bulk chemistry. PMID:23893032

  9. Abnormal T cell subpopulations and circulating immune complexes in the Guillain-Barré syndrome and multiple sclerosis.

    PubMed

    Goust, J M; Chenais, F; Carnes, J E; Hames, C G; Fudenberg, H H; Hogan, E L

    1978-05-01

    Immunologic studies were performed in 21 patients with multiple sclerosis (MS) and 16 with the Guillain-Barré syndrome (GBS). Levels of thymus-derived (T) cells measured by "total" and "active" rosette formation between sheep erythrocytes and peripheral blood mononuclear cells (TEt, TEa) were within normal limits in all the patients, with the exception of four GBS patients, including one who also had received chemotherapy for lymphoma and three who were receiving steroids. When lymphocytes from the 21 patients were incubated with the bone-marrow-derived (B) lymphoblastoid cell line PGLC-33H, there were, for 12 of 18 MS patients and 11 of 16 GBS patients, significant decreases in a subpopulation of peripheral blood T lymphocytes that form "PGLC rosettes" (PGR) with the PGLC-33H cells. (Peripheral blood T cells from normal individuals formed PGR with 23.9 +/- 3.8 percent of PGLC-33H cells.) Using the 125l-C1q binding assay, immune complexes were detected in the serum of 14 of 19 MS patients and 15 of 16 GBS patients. An association between increased C1q binding and decreased PGR values was found in 10 of 18 MS patients and 12 of 17 GBS patients. The results suggest that in both diseases the etiology may involve a decrease in the subset of T cells that bind to the IgM-producing cell line PGLC-33H, in association with the appearance of circulating immune complexes containing the infectious viral agent. PMID:306075

  10. Solid oxide fuel cell electrolytes produced by a combination of suspension plasma spray and very low pressure plasma spray.

    SciTech Connect

    Slamovich, Elliot; Fleetwood, James; McCloskey, James F.; Hall, Aaron Christopher; Trice, Rodney Wayne

    2010-07-01

    Plasma spray coating techniques allow unique control of electrolyte microstructures and properties as well as facilitating deposition on complex surfaces. This can enable significantly improved solid oxide fuel cells (SOFCs), including non-planar designs. SOFCs are promising because they directly convert the oxidization of fuel into electrical energy. However, electrolytes deposited using conventional plasma spray are porous and often greater than 50 microns thick. One solution to form dense, thin electrolytes of ideal composition for SOFCs is to combine suspension plasma spray (SPS) with very low pressure plasma spray (VLPPS). Increased compositional control is achieved due to dissolved dopant compounds in the suspension that are incorporated into the coating during plasma spraying. Thus, it is possible to change the chemistry of the feed stock during deposition. In the work reported, suspensions of sub-micron diameter 8 mol.% Y2O3-ZrO2 (YSZ) powders were sprayed on NiO-YSZ anodes at Sandia National Laboratories (SNL) Thermal Spray Research Laboratory (TSRL). These coatings were compared to the same suspensions doped with scandium nitrate at 3 to 8 mol%. The pressure in the chamber was 2.4 torr and the plasma was formed from a combination of argon and hydrogen gases. The resultant electrolytes were well adhered to the anode substrates and were approximately 10 microns thick. The microstructure of the resultant electrolytes will be reported as well as the electrolyte performance as part of a SOFC system via potentiodynamic testing and impedance spectroscopy.

  11. The effect of plasma jet on morphology of the apoptosis cancer cell

    NASA Astrophysics Data System (ADS)

    Mirpour, Shahriar; Nikkhah, Maryam; Pirouzmand, Somaye; Ghomi, Hamid Reza

    2012-10-01

    In recent years, many studies have been carried out to understand the effect of non-thermal plasma on cancer cells. The previous studies showed that non-thermal plasma has apoptosis effect on cancer cells. Also they discovered that after plasma treatment three distinct regions (Death cells, Void zone and live cells) were observed in wells treated [1]. The aim of this paper is to study the effect of plasma jet on these three regions. For this purpose a variable voltage power supply with 20 kHz frequency are used experimentally. The results showed the detached cells rate were increased by increasing the voltage. [4pt] [1] A. Shashurin, M. Keidar, S. Bronnikov, R. A. Jurjus, and M. A. Stepp, Appl. Phys. Lett. 93, 181501 (2008), DOI:10.1063/1.3020223

  12. Abnormal Expression of REST/NRSF and Myc in Neural Stem/Progenitor Cells Causes Cerebellar Tumors by Blocking Neuronal Differentiation

    PubMed Central

    Su, Xiaohua; Gopalakrishnan, Vidya; Stearns, Duncan; Aldape, Kenneth; Lang, Fredrick F.; Fuller, Gregory; Snyder, Evan; Eberhart, Charles G.; Majumder, Sadhan

    2006-01-01

    Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a previously established cell line derived from external granule layer stem cells transduced with activated c-myc (NSC-M). These immortalized NSCs were able to differentiate into neurons in vitro. In contrast, when the cells were engineered to express a doxycycline-regulated REST/NRSF transgene (NSC-M-R), they no longer underwent terminal neuronal differentiation in vitro. When injected into intracranial locations in mice, the NSC-M cells did not form tumors either in the cerebellum or in the cerebral cortex. In contrast, the NSC-M-R cells did produce tumors in the cerebellum, the site of human medulloblastoma formation, but not when injected into the cerebral cortex. Furthermore, the NSC-M-R tumors were blocked from terminal neuronal differentiation. In addition, countering REST/NRSF function blocked the tumorigenic potential of NSC-M-R cells. To our knowledge, this is the first study in which abnormal expression of a sequence-specific DNA-binding transcriptional repressor has been shown to contribute directly to brain tumor formation. Our findings indicate that abnormal expression of REST/NRSF and Myc in NSCs causes cerebellum-specific tumors by blocking neuronal differentiation and thus maintaining the “stemness” of these cells. Furthermore

  13. DNA damage in oral cancer cells induced by nitrogen atmospheric pressure plasma jets

    NASA Astrophysics Data System (ADS)

    Han, Xu; Klas, Matej; Liu, Yueying; Sharon Stack, M.; Ptasinska, Sylwia

    2013-06-01

    The nitrogen atmospheric pressure plasma jet (APPJ) was applied to induce DNA damage of SCC-25 oral cancer cells. Optical emission spectra were taken to characterize the reactive species produced in APPJ. In order to explore the spatial distribution of plasma effects, cells were placed onto photo-etched grid slides and the antibody H2A.X was used to locate double strand breaks of DNA inside nuclei using an immunofluorescence assay. The number of cells with double strand breaks in DNA was observed to be varied due to the distance from the irradiation center and duration of plasma treatment.

  14. Micro-plasma Luminescence And Signal Noise Used To Solar Cells Defects Diagnostic

    NASA Astrophysics Data System (ADS)

    Jiri, Vanek; Pavel, Koktavy; Jan, Dolensky; Ales, Vesely; Zdenek, Chobola; Petr, Paracka

    2009-04-01

    This work deals with the usage of signal noise and micro-plasmas luminescence for solar cells diagnostic. When high electric field is applied to PN junction of solar cell with some technological imperfections it produces in tiny areas of enhanced impact ionization called micro-plasmas which could lead to deterioration in quality or destruction of PN junction. On this account it is possible to use methods which indicate presence of micro-plasma in junction and enable quality and quantitative description of tested cells.

  15. Cutaneous manifestations of multiple myeloma and other plasma cell proliferative disorders.

    PubMed

    Bhutani, Manisha; Shahid, Zainab; Schnebelen, Alicia; Alapat, Daisy; Usmani, Saad Z

    2016-06-01

    Plasma cell proliferative disorders cause rare but extremely varied dermatologic manifestations that may occur as an accompaniment to established diagnoses, or may be a first clue of an underlying neoplasm in the setting of clinical suspicion. In some instances skin lesions result from aggregation of misfolded monoclonal immunoglobulins or their fragments, as in light chain-related systemic amyloidosis. On other occasions the cutaneous lesions result from deposits of malignant plasma cells or monoclonal proteins. In still others, the dermatologic manifestations are related to antibody activity of monoclonal protein, as in many cases of cryoglobulinemia. This report provides insights into the well-recognized cutaneous manifestations associated with plasma cell disorders. PMID:27178694

  16. [Plasma cell leukemia: three case-reports and review of literature].

    PubMed

    Eddou, Hicham; Mahtat, El Mehdi; Zahid, Hamid; Maaroufi, Hicham El; Jennane, Selim; Messaoudi, Nezha; Doghmi, Kamal; Mikdame, Mohamed

    2013-01-01

    Plasma cell leukemia (LP) is a rare hematologic malignancy. Its prognosis is very derogatory. It is defined by the presence in circulating blood of more than 2 G/L plasmocytes or greater than 20% of the total leukocytes. It comes in two forms: secondary plasma cell leukemia complicating multiple myeloma (MM) and primary setting. Its incidence is estimated at 0.9% of patients with acute leukemia and 2-4% of patients with MM. We report, through three observations, the clinical presentation of the plasma cell leukemia, its cytological features, immunophenotypic, physiopathological and therapeutic care. PMID:24342791

  17. DNA damage in oral cancer cells induced by nitrogen atmospheric pressure plasma jets

    SciTech Connect

    Han, Xu; Ptasinska, Sylwia; Klas, Matej; Liu, Yueying; Sharon Stack, M.

    2013-06-10

    The nitrogen atmospheric pressure plasma jet (APPJ) was applied to induce DNA damage of SCC-25 oral cancer cells. Optical emission spectra were taken to characterize the reactive species produced in APPJ. In order to explore the spatial distribution of plasma effects, cells were placed onto photo-etched grid slides and the antibody H2A.X was used to locate double strand breaks of DNA inside nuclei using an immunofluorescence assay. The number of cells with double strand breaks in DNA was observed to be varied due to the distance from the irradiation center and duration of plasma treatment.

  18. Plasma cell leukemia: A case series from South India with emphasis on rarer variants

    PubMed Central

    Rajeswari, G.; Paul, T. Roshni; Uppin, Megha S.; Uppin, Shantveer G.; Rao, D. Raghunadha; Raju D, D. Sree Bhushan; Sadashindu, G.

    2014-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasia. They occur de novo (primary) or as a late manifestation of multiple myeloma (secondary). Patients present with anemia, thrombocytopenia, renal failure, organomegaly and extramedullary manifestations. We are presenting this series as it is the second largest series from India (16) with 4 young cases (under 40 years of age), more number of female patients and two having ‘hairy cell’ morphology. It is recommended that techniques like immunophenotyping and protein electrophoresis be performed, whenever the morphology is not characteristic of plasma cells. PMID:25336792

  19. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation

    PubMed Central

    2010-01-01

    Background Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX. Results We report the construction and initial characterization of a mouse model expressing the A140V MeCP2 mutation. These initial descriptive studies in male hemizygous mice have revealed brain abnormalities seen in both RTT and mental retardation. The abnormalities found include increases in cell packing density in the brain and a significant reduction in the complexity of neuronal dendritic branching. In contrast to some MeCP2 mutation mouse models, the A140V mouse has an apparently normal lifespan and normal weight gain patterns with no obvious seizures, tremors, breathing difficulties or kyphosis. Conclusion We have identified various neurological abnormalities in this mouse model of Rett syndrome/X-linked mental retardation which may help to elucidate the manner in which MECP2 mutations cause neuronal changes resulting in mental retardation without the confounding effects of seizures, chronic hypoventilation, or other Rett syndrome associated symptoms. PMID:20163734

  20. Roles of the plasma membrane and the cell wall in the responses of plant cells to freezing.

    PubMed

    Yamada, Tomoyoshi; Kuroda, Katsushi; Jitsuyama, Yutaka; Takezawa, Daisuke; Arakawa, Keita; Fujikawa, Seizo

    2002-09-01

    In an effort to clarify the responses of a wide range of plant cells to freezing, we examined the responses to freezing of the cells of chilling-sensitive and chilling-resistant tropical and subtropical plants. Among the cells of the plants that we examined, those of African violet ( Saintpaulia grotei Engl.) leaves were most chilling-sensitive, those of hypocotyls in mungbean [ Vigna radiata (L.) R. Wilcz.] seedlings were moderately chilling-sensitive, and those of orchid [ Paphiopedilum insigne (Wallich ex Lindl.) Pfitz.] leaves were chilling-resistant, when all were chilled at -2 degrees C. By contrast, all these plant cells were freezing-sensitive and suffered extensive damage when they were frozen at -2 degrees C. Cryo-scanning electron microscopy (Cryo-SEM) confirmed that, upon chilling at -2 degrees C, both chilling-sensitive and chilling-resistant plant cells were supercooled. Upon freezing at -2 degrees C, by contrast, intracellular freezing occurred in Saintpaulia leaf cells, frost plasmolysis followed by intracellular freezing occurred in mungbean seedling cells, and extracellular freezing (cytorrhysis) occurred in orchid leaf cells. We postulate that chilling-related destabilization of membranes might result in the loss of the ability of the plasma membrane to act as a barrier against the propagation of extracellular ice in chilling-sensitive plant cells. We also examined the role of cell walls in the response to freezing using cells in which the plasma membrane had been disrupted by repeated freezing and thawing. In chilling-sensitive Saintpaulia and mungbean cells, the cells with a disrupted plasma membrane responded to freezing at -2 degrees C by intracellular freezing. By contrast, in chilling-resistant orchid cells, as well as in other cells of chilling-resistant and freezing-resistant plant tissues, including leaves of orchard grass ( Dactylis glomerata L.), leaves of Arabidopsis thaliana (L.) Heynh. and cortical tissues of mulberry ( Morus

  1. Skeletal cell differentiation is enhanced by atmospheric dielectric barrier discharge plasma treatment.

    PubMed

    Steinbeck, Marla J; Chernets, Natalie; Zhang, Jun; Kurpad, Deepa S; Fridman, Gregory; Fridman, Alexander; Freeman, Theresa A

    2013-01-01

    Enhancing chondrogenic and osteogenic differentiation is of paramount importance in providing effective regenerative therapies and improving the rate of fracture healing. This study investigated the potential of non-thermal atmospheric dielectric barrier discharge plasma (NT-plasma) to enhance chondrocyte and osteoblast proliferation and differentiation. Although the exact mechanism by which NT-plasma interacts with cells is undefined, it is known that during treatment the atmosphere is ionized generating extracellular reactive oxygen and nitrogen species (ROS and RNS) and an electric field. Appropriate NT-plasma conditions were determined using lactate-dehydrogenase release, flow cytometric live/dead assay, flow cytometric cell cycle analysis, and Western blots to evaluate DNA damage and mitochondrial integrity. We observed that specific NT-plasma conditions were required to prevent cell death, and that loss of pre-osteoblastic cell viability was dependent on intracellular ROS and RNS production. To further investigate the involvement of intracellular ROS, fluorescent intracellular dyes Mitosox (superoxide) and dihydrorhodamine (peroxide) were used to assess onset and duration after NT-plasma treatment. Both intracellular superoxide and peroxide were found to increase immediately post NT-plasma treatment. These increases were sustained for one hour but returned to control levels by 24 hr. Using the same treatment conditions, osteogenic differentiation by NT-plasma was assessed and compared to peroxide or osteogenic media containing β-glycerolphosphate. Although both NT-plasma and peroxide induced differentiation-specific gene expression, neither was as effective as the osteogenic media. However, treatment of cells with NT-plasma after 24 hr in osteogenic or chondrogenic media significantly enhanced differentiation as compared to differentiation media alone. The results of this study show that NT-plasma can selectively initiate and amplify ROS signaling to enhance

  2. Skeletal Cell Differentiation Is Enhanced by Atmospheric Dielectric Barrier Discharge Plasma Treatment

    PubMed Central

    Zhang, Jun; Kurpad, Deepa S.; Fridman, Gregory; Fridman, Alexander; Freeman, Theresa A.

    2013-01-01

    Enhancing chondrogenic and osteogenic differentiation is of paramount importance in providing effective regenerative therapies and improving the rate of fracture healing. This study investigated the potential of non-thermal atmospheric dielectric barrier discharge plasma (NT-plasma) to enhance chondrocyte and osteoblast proliferation and differentiation. Although the exact mechanism by which NT-plasma interacts with cells is undefined, it is known that during treatment the atmosphere is ionized generating extracellular reactive oxygen and nitrogen species (ROS and RNS) and an electric field. Appropriate NT-plasma conditions were determined using lactate-dehydrogenase release, flow cytometric live/dead assay, flow cytometric cell cycle analysis, and Western blots to evaluate DNA damage and mitochondrial integrity. We observed that specific NT-plasma conditions were required to prevent cell death, and that loss of pre-osteoblastic cell viability was dependent on intracellular ROS and RNS production. To further investigate the involvement of intracellular ROS, fluorescent intracellular dyes Mitosox (superoxide) and dihydrorhodamine (peroxide) were used to assess onset and duration after NT-plasma treatment. Both intracellular superoxide and peroxide were found to increase immediately post NT-plasma treatment. These increases were sustained for one hour but returned to control levels by 24 hr. Using the same treatment conditions, osteogenic differentiation by NT-plasma was assessed and compared to peroxide or osteogenic media containing β-glycerolphosphate. Although both NT-plasma and peroxide induced differentiation-specific gene expression, neither was as effective as the osteogenic media. However, treatment of cells with NT-plasma after 24 hr in osteogenic or chondrogenic media significantly enhanced differentiation as compared to differentiation media alone. The results of this study show that NT-plasma can selectively initiate and amplify ROS signaling to enhance

  3. CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance.

    PubMed Central

    Zandecki, M; Facon, T; Bernardi, F; Izydorczyk, V; Dupond, L; François, M; Reade, R; Iaru, T; Bauters, F; Cosson, A

    1995-01-01

    AIMS--To determine whether a particular phenotype or antigen is preferentially related to monoclonal gammopathies of undetermined significance (MGUS). METHODS--Bone marrow specimens from 56 patients with MGUS were stained immunocytochemically (ABC peroxidase) for CD38, CD56, CD9, CD10, CD19, CD20, CD22, and MB2. Specimens from patients recently diagnosed with multiple myeloma and reactive bone marrow samples were studied in parallel. RESULTS--CD38 was expressed on all plasma cells from all MGUS samples tested, while 36% were positive for CD56, CD9 and MB2 were both expressed strongly; CD20 was moderately expressed, and staining for CD10 and CD22 was uncommon. For these five B cell antigens there was no clear difference between their expression in MGUS and in multiple myeloma. A great difference was found for CD19: in MGUS this antigen was expressed on 2-91% of plasma cells (mean 35%) and 77% patients had > 10% positive plasma cells; in multiple myeloma its expression was low and only 12% patients had > 10% positive plasma cells. When these results were converted to numbers of CD19 positive plasma cells per 100 nucleated bone marrow cells, reactive bone marrow and MGUS specimens had a similar number of positive plasma cells. There was no correlation between expression of any of the antigens tested. CONCLUSIONS--Many of the so-called pre-B, B or activation antigens are present on plasma cells from MGUS specimens, and expression of CD9, CD10, CD20, CD22, MB2, and CD38 in MGUS was very similar to that in multiple myeloma. CD56 was frequently expressed in MGUS. In this series CD19 was highly expressed in MGUS but not in multiple myeloma. Plasma cells bearing this antigen could represent the non-neoplastic process and determination of its expression could be useful for the diagnosis of MGUS. PMID:7545187

  4. Abnormal Histone Methylation is Responsible for Increased VEGF165a Secretion from Airway Smooth Muscle Cells in Asthma

    PubMed Central

    Clifford, Rachel L.; John, Alison E.; Brightling, Christopher E.; Knox, Alan J.

    2012-01-01

    Vascular Endothelial Growth Factor (VEGF), a key angiogenic molecule, is aberrantly expressed in several diseases including asthma where it contributes to bronchial vascular remodelling and chronic inflammation. Asthmatic human airway smooth muscle (HASM) cells hypersecrete VEGF but the mechanism is unclear. Here we defined the mechanism in HASM cells from non-asthmatic (NA) and asthmatic (A) patients. We found that asthmatic cells lacked a repression complex at the VEGF promoter which was present in non-asthmatic cells. Recruitment of G9A, trimethylation of histone H3 at lysine 9 (H3K9me3) and a resultant decrease in RNA polymerase II (RNA pol II) at the VEGF promoter was critical to repression of VEGF secretion in non-asthmatic cells. At the asthmatic promoter H3K9me3 was absent due to failed recruitment of G9a; RNA pol II binding, in association with TAF1, was increased, H3K4me3 was present and Sp1 binding was exaggerated and sustained. In contrast DNA methylation and histone acetylation were similar in A and NA cells. This is the first study to show that airway cells in asthma have altered epigenetic regulation of remodelling gene(s). Histone methylation at genes such as VEGF may be an important new therapeutic target. PMID:22689881

  5. The connection of cytoskeletal network with plasma membrane and the cell wall

    PubMed Central

    Liu, Zengyu; Persson, Staffan; Zhang, Yi

    2015-01-01

    The cell wall provides external support of the plant cells, while the cytoskeletons including the microtubules and the actin filaments constitute an internal framework. The cytoskeletons contribute to the cell wall biosynthesis by spatially and temporarily regulating the transportation and deposition of cell wall components. This tight control is achieved by the dynamic behavior of the cytoskeletons, but also through the tethering of these structures to the plasma membrane. This tethering may also extend beyond the plasma membrane and impact on the cell wall, possibly in the form of a feedback loop. In this review, we discuss the linking components between the cytoskeletons and the plasma membrane, and/or the cell wall. We also discuss the prospective roles of these components in cell wall biosynthesis and modifications, and aim to provide a platform for further studies in this field. PMID:25693826

  6. Treatment of oral cancer cells with nonthermal atmospheric pressure plasma jet

    NASA Astrophysics Data System (ADS)

    Yurkovich, James; Han, Xu; Coffey, Benjamin; Klas, Matej; Ptasinska, Sylwia

    2012-10-01

    Non-thermal atmospheric pressure plasmas are specialized types of plasma that are proposed as a new agent to induce death in cancer cells. The experimental phase of this study will test the application of such plasma to SCC-25 oral cancer cells to determine if it is possible to induce apoptosis or necrosis. Different sources are used on the cells to find a configuration which kills cancer cells but has no effect on normal cells. The sources have been developed based on the dielectric barrier discharge between two external electrodes surrounding a dielectric tube; such a configuration has been shown to induce breaks in DNA strands. Each configuration is characterized using an optical emission spectrophotometer and iCCD camera to determine the optimal conditions for inducing cell death. The cells are incubated after irradiation with plasma, and cell death is determined using microscopy imaging to identify antibody interaction within the cells. These studies are important for better understanding of plasma species interactions with cancer cells and mechanisms of DNA damage and at latter stage they will be useful for the development of advanced cancer therapy.

  7. Targeting NEU Protein in Melanoma Cells with Non-Thermal Atmospheric Pressure Plasma and Gold Nanoparticles.

    PubMed

    Choi, Byul Bora; Kim, Myung Soo; Kim, Uk Kyu; Hong, Jin Woo; Lee, Hae June; Kim, Gyoo Cheon

    2015-05-01

    Non-thermal atmospheric pressure plasma effectively kills cancer cells, but it cannot selectively kill cancer cells. The authors targeted NEU (human epidermal growth factor receptor 2) protein, which is frequently over-expressed in the cell membrane of melanoma cells, using anti-NEU antibody-labeled gold nanoparticles. The labeled nanoparticles preferentially targeted melanoma cells rather than normal keratinocytes. After the addition of labeled gold nanoparticles to melanoma and normal keratinocyte cells, both cells were exposed to non-thermal atmospheric pressure plasma. The death rate of melanoma cells was significantly higher than that of normal keratinocyte cells; many vacuoles, indicative of cell death, were observed in melanoma cells treated with anti-NEU antibody labeled gold nanoparticles and plasma. This selective cancer cell death was attributed to the selective destruction of NEU protein and a downstream effector of NEU. Our study findings show that treatment with a combination of non-thermal atmospheric pressure plasma and anti-NEU antibody-labeled gold nanoparticles effectively and selectively kills melanoma cells. PMID:26349401

  8. Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

    PubMed Central

    Ristau, Benjamin T.; Kamat, Sonal N.; Tarin, Tatum V.

    2015-01-01

    The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of “pseudohypoxia,” inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome. PMID:26380143

  9. Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

    PubMed

    Ristau, Benjamin T; Kamat, Sonal N; Tarin, Tatum V

    2015-01-01

    The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome. PMID:26380143

  10. Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.

    PubMed

    Wang, Li; Xing, Jie; Cheng, Rui; Shao, Ying; Li, Peng; Zhu, Shengtao; Zhang, Shutian

    2015-01-01

    Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study. PMID:25950810

  11. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  12. Loss of cyclin-dependent kinase inhibitor genes and chromosome 9 karyotypic abnormalities in human bladder cancer cell lines.

    PubMed Central

    Southgate, J.; Proffitt, J.; Roberts, P.; Smith, B.; Selby, P.

    1995-01-01

    Loss of cell cycle control through the structural or functional aberration of checkpoint genes and their products is a potentially important process in carcinogenesis. In this study, a panel of well-characterised established human bladder cancer cell lines was screened by the polymerase chain reaction for homozygous loss of the cyclin-dependent kinase inhibitor genes p15, p16 and p27. The results demonstrate that, whereas there was no genetic loss of p27, homozygous deletion of both p15 and p16 genes occurred in seven of 13 (54%) independent bladder cell lines tested. Differential loss of either the p15 or p16 gene was not seen. The p15 and p16 genes are known to be juxtaposed on chromosome 9p21 at the locus of a putative tumour-suppressor gene involved in the initiation of bladder cancer. Cytogenetic analysis of the cell lines revealed karyotypes ranging from near diploid to near pentaploid with complex rearrangements of some chromosomes and a high prevalence of chromosome 9p rearrangements, although all cell lines contained at least one cytogenetically normal 9p21 region. These observations support a role for p15/p16 gene inactivation in bladder carcinogenesis and/or the promotion of cell growth in vitro and lend support to the hypothesis that homozygous deletion centred on 9p21 is a mechanism by which both p15 and p16 genes are co-inactivated. Images Figure 1 Figure 2 Figure 3 PMID:7577470

  13. AT14A mediates the cell wall-plasma membrane-cytoskeleton continuum in Arabidopsis thaliana cells.

    PubMed

    Lü, Bing; Wang, Juan; Zhang, Yu; Wang, Hongcheng; Liang, Jiansheng; Zhang, Jianhua

    2012-06-01

    AT14A has a small domain that has sequence similarities to integrins from animals. Integrins serve as a transmembrane linker between the extracellular matrix and the cytoskeleton, which play critical roles in a variety of biological processes. Because the function of AT14A is unknown, Arabidopsis thaliana AT14A, which is a transmembrane receptor for cell adhesion molecules and a middle member of the cell wall-plasma membrane-cytoskeleton continuum in plants, has been described. AT14A, co-expressed with green fluorescent protein (GFP), was found to localize mainly to the plasma membrane. The mutant Arabidopsis at14a-1 cells exhibit various phenotypes with cell shape, cell cluster size, thickness, and cellulose content of cell wall, the adhesion between cells, and the adhesion of plasma membrane to cell wall varied by plasmolysis. Using direct staining of filamentous actin and indirect immunofluorescence staining of microtubules, cortical actin filaments and microtubules arrays were significantly altered in cells, either where AT14A was absent or over-expressed. It is concluded that AT14A may be a substantial middle member of the cell wall-plasma membrane-cytoskeleton continuum and play an important role in the continuum by regulating cell wall and cortical cytoskeleton organization. PMID:22456678

  14. [Classification and genetic abnormalities of multiple myeloma].

    PubMed

    Hanamura, Ichiro; Iida, Shinsuke

    2015-01-01

    Multiple myeloma (MM) is a malignancy of plasma cells which develops through genetic aberrations, epigenetic changes and the bone marrow microenvironment interaction. Despite recent tremendous progress in treatments for MM, a complete cure remains elusive. Further development of more effective therapeutic strategies is needed. The International Staging System (ISS) reported in 2005 has been used widely as the most simple and powerful prognostic classification in MM, but genetic abnormalities affecting prognosis were not considered in this model. In the past decade, non-random chromosomal aberrations such as t(4;14), t(14;16), t(14;20), amp1q21 and del17p have shown to be poor prognostic value, and moreover, recent progress in genome-wide deep sequencing studies has revealed novel mutations and intra-tumor subclonal heterogeneity which may explain clinical phenotype and therapeutic resistance. Here we review the current understanding of genetic abnormalities in MM for developing better prognostic classification and molecular targeted therapies leading to the stratified or personalized medicine. PMID:25626298

  15. Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling.

    PubMed

    Nambiar, Madhusoodana P; Warke, Vishal G; Fisher, Carolyn U; Tsokos, George C

    2002-01-01

    Trichostatin A (TSA) is a potent reversible inhibitor of histone deacetylase, and it has been reported to have variable effects on the expression of a number of genes. In this report, we show that TSA suppresses the expression of the T cell receptor zeta chain gene, whereas, it upregulates the expression if its homologous gene Fc(epsilon) receptor I gamma chain. These effects are associated with decreased intracytoplasmic-free calcium responses and altered tyrosine phosphorylation pattern of cytosolic proteins. Along with these effects, we report that TSA suppresses the expression of the interleukin-2 gene. The effects of TSA on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations that have been described in patients with systemic lupus erythematosus. PMID:11967985

  16. Translocation t(2;7)(p11;q21) associated with the CDK6/IGK rearrangement is a rare but recurrent abnormality in B-cell lymphoproliferative malignancies.

    PubMed

    Douet-Guilbert, Nathalie; Tous, Corinne; Le Flahec, Glen; Bovo, Clément; Le Bris, Marie-Josée; Basinko, Audrey; Morel, Frédéric; De Braekeleer, Marc

    2014-03-01

    Structural abnormalities of chromosome 7q have been regularly reported in chronic B-cell lymphoproliferative disorders. They include chromosomal translocations involving 7q21, leading to overexpression of the CDK6 gene. Three different translocations, t(7;14)(q21;q32), t(7;22)(q21;q11), and t(2;7)(p11;q21), leading to the juxtaposition of the CDK6 gene with a immunoglobulin gene enhancer during B-cell differentiation, have been described. In the past 2 years, we identified three patients with lymphoproliferative malignancy associated with a t(2;7)(p11;q21). Fluorescent in situ hybridization using an IGK probe and a library of bacterial artificial chromosome (BAC) clones located in bands 7q21.2 and 7q21.3, containing CDK6, revealed that the telomeric part of the IGK probe was translocated on the der(7) within a 51-kb region upstream of the transcriptional start site of CDK6. A total of 23 patients with indolent B-cell lymphoproliferative disorders and juxtaposition of the IG and CDK6 genes, including 20 with IGK and CDK6 juxtaposition, have been reported thus far. This rearrangement leads to the overexpression of CDK6, which encodes a cyclin-dependent protein kinase involved in cell cycle G1 phase progression and G1/S transition. PMID:24726269

  17. Effect of damage removal etch (DRE) on plasma textured, multi-crystalline solar cells

    NASA Astrophysics Data System (ADS)

    Majumdar, S.; Pathak, M.; Chahar, N.; Sharan, A.; Saxena, A. K.; Bhattacharya, S.

    2014-10-01

    In the present work, a self-masked, dry, plasma texturing process for multi crystalline silicon (mc-Si) wafers has been developed that results in a higher cell performance than that with un-textured wafers. Plasma textured samples prepared have low levels (∼4%) of reflectance. Plasma damage of textured wafers has been eliminated by a damage removal etch (DRE). The improvement in efficiency of mc-Si solar cells up to 15.1% has been attributed to complete suppression of reflectivity (4-5%) in a broad spectral range (350-800 nm) leading to black silicon surface. Also, DRE on plasma textured wafers has been found to result in reduced surface damage compared to cells without DRE leading to higher cell efficiencies.

  18. Spontaneous rupture of the spleen in primary plasma cell leukemia. Scintigraphic-pathologic correlation

    SciTech Connect

    Kienzle, G.D.; Stern, J.; Cooperberg, A.; Osborne, C.A.

    1985-09-01

    A rare case of spontaneous rupture of the spleen occurring in a patient with primary plasma cell leukemia is presented. The scintigraphic-pathologic correlation is presented together with a review of the literature.

  19. Plasma Membrane Lesions In Anthracycline-Resistant Tumor Cells Probed Using A Fluorescent Dye

    NASA Astrophysics Data System (ADS)

    Burke, Thomas G.; Doroshow, James H.

    1989-06-01

    Human cancer cells selected for resistance to several structurally unrelated cytotoxic drugs are known to display plasma membrane alterations such as amplified levels of a variety of glycoproteins, modifications in lipid composition, alterations in membrane fluidity and increased cellular fragility to osmotic shock. We have studied the plasma membrane fluidity of HL60 human leukemia cells and MCF-7 human breast cancer cells that have been selected for acquired resistance against the cytocidal effects of the anthracycline anticancer drug Adriamycin. Fluidity measurements were accomplished by evaluating the fluorescence anisotropy of the plasma membrane specific probe trimethylamino-1,6-dipihenylhexatriene (TMA.DPH) bound to whole, living cells. TMA.DPH anisotropy values for MCF-7 sensitive and 12-fold resistant cells were 0.306 and 0.285, respectively, while anisotropy values for HL-60 sensitive and 80-fold resistant cells lines were 0.310 and 0.295, respectively. In all cases, cell viability exceeded 97% and anisotropy values were subject to a day-to-day uncertainty of +/-2%. Our results demonstrate that increased plasma membrane fluidity apparently accompanies the development of resistance in both cell lines. Because it is known that increased membrane fluidity results in significantly decreased Adriamycin binding in artificial membrane systems, we propose here that decreased drug associations with fluidized, plasma membrane lipid bilayer regions may be a mechanism which contributes, in part, to the reduced rates of drug accumulation observed in HL60 and MCF-7 cells resistant to Adriamycin.

  20. DNT cell inhibits the growth of pancreatic carcinoma via abnormal expressions of NKG2D and MICA in vivo.

    PubMed

    Xu, Hong; Zhu, Xing-Xing; Chen, Jiong

    2016-01-01

    This research aimed to investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class I chain-related molecules A(MICA) in DNT cell killing pancreatic carcinoma. Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice. Then randomly divided mice into blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. 50 days later mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. DNT cell significantly increased over time. The blank group tumor volume and weight were significantly larger than the other groups (p < 0.001, p < 0.001), but there were no significantly difference between DNT group and gemcitabine group (p > 0.05). Gemcitabine and DNT cell tumor inhibition rate were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than DNT group (p = 0.001, p = 0.003). NKG2D mRNA and protein levels in blank group were significantly lower than DNT cells group (p < 0.001, p = 0.001). In conclusion DNT cell can significantly inhibit the growth of pancreatic carcinoma in vivo, and the mechanism may be involved in abnormal expressions of MICA and NKG2D. PMID:26616050

  1. Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer.

    PubMed

    Berntsson, Jonna; Nodin, Björn; Eberhard, Jakob; Micke, Patrick; Jirström, Karin

    2016-09-01

    Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p < 0.001, p < 0.001, and p = 0.006, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.53, 95% CI 0.36-0.78), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study. PMID:27074317

  2. Binding of human myeloperoxidase to red blood cells: Molecular targets and biophysical consequences at the plasma membrane level.

    PubMed

    Gorudko, Irina V; Sokolov, Alexey V; Shamova, Ekaterina V; Grigorieva, Daria V; Mironova, Elena V; Kudryavtsev, Igor V; Gusev, Sergey A; Gusev, Alexander A; Chekanov, Andrey V; Vasilyev, Vadim B; Cherenkevich, Sergey N; Panasenko, Oleg M; Timoshenko, Alexander V

    2016-02-01

    Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also bind to cellular surface proteins. We found that band 3 protein and glycophorins A and B were the key MPO-binding targets of human red blood cells (RBCs). The interaction of MPO with RBC proteins was mostly electrostatic in nature because it was inhibited by desialation, exogenic sialic acid, high ionic strength, and extreme pH. In addition, MPO failed to interfere with the lectin-induced agglutination of RBCs, suggesting a minor role of glycan-recognizing mechanisms in MPO binding. Multiple biophysical properties of RBCs were altered in the presence of native (i.e., not hypochlorous acid-damaged) MPO. These changes included transmembrane potential, availability of intracellular Ca(2+), and lipid organization in the plasma membrane. MPO-treated erythrocytes became larger in size, structurally more rigid, and hypersensitive to acidic and osmotic hemolysis. Furthermore, we found a significant correlation between the plasma MPO concentration and RBC rigidity index in type-2 diabetes patients with coronary heart disease. These findings suggest that MPO functions as a mediator of novel regulatory mechanism in microcirculation, indicating the influence of MPO-induced abnormalities on RBC deformability under pathological stress conditions. PMID:26714302

  3. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  4. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  5. Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

    MedlinePlus

    ... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

  6. Long-term remission of pure red cell aplasia after plasma exchange and lymphocytapheresis.

    PubMed

    Berlin, G; Liedén, G

    1986-01-01

    A 57-year-old man with idiopathic pure red cell aplasia went into remission after plasma exchange. He relapsed after 5 months and then failed to respond to treatment with intensive plasma exchange and immunosuppressive agents. Because of a high proportion of T-suppressor cells in the peripheral blood he was treated with lymphocytapheresis in addition to the previous treatment. The patient achieved a long-term haematological remission which has now persisted for more than 3 yr. PMID:2937136

  7. The use of antioxidative stress enzymes, lipid peroxidation, and red blood cell abnormalities as biomarkers of stress in Periphthalmus papilio of the polluted coastal Lagos lagoon.

    PubMed

    Nnamdi, Amaeze H; Olumide, Adebesin A; Adeladun, Adepegba E; Oyenike, Kolapo; Rosemary, Egonmwan I

    2015-03-01

    We assessed the mudskipper, Periphthalmus papilio inhabiting the coast line of the Lagos lagoon, Gulf of Guinea, to determine suitable biomarkers of stress due to its current status as a polluted water body. The gill and liver samples showed evidence of some activities of antioxidative stress enzymes including catalase, superoxide dismutase, glutathione-s-transferase, reduced glutahthione, as well as some detectable levels of lipid peroxidation product. The stress status of the fishes was also elucidated by nuclear abnormalities especially micronucleus formation and the presence of numerous vacuolated red blood cells. Given the current need for more sensitive bioindicators in monitoring pollution in this lagoon, we hereby present these inherent responses in P. papilio as a suitable candidate for incorporation into the current repertoire for ecotoxicological investigations in polluted water bodies of the Gulf of Guinea coastline. PMID:25666650

  8. Production of intracellular reactive oxygen species and change of cell viability induced by atmospheric pressure plasma in normal and cancer cells

    NASA Astrophysics Data System (ADS)

    Ja Kim, Sun; Min Joh, Hea; Chung, T. H.

    2013-10-01

    The effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. Using a detection dye, the production of intracellular reactive oxygen species (ROS) was found to be increased in plasma-treated cells compared to non-treated and gas flow-treated cells. A significant overproduction of ROS and a reduction in cell viability were induced by plasma exposure on cancer cells. Normal cells were observed to be less affected by the plasma-mediated ROS, and cell viability was less changed. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as a cancer therapy.

  9. Exogenous nitric oxide (NO) generated by NO-plasma treatment modulates osteoprogenitor cells early differentiation

    NASA Astrophysics Data System (ADS)

    Elsaadany, Mostafa; Subramanian, Gayathri; Ayan, Halim; Yildirim-Ayan, Eda

    2015-09-01

    In this study, we investigated whether nitric oxide (NO) generated using a non-thermal plasma system can mediate osteoblastic differentiation of osteoprogenitor cells without creating toxicity. Our objective was to create an NO delivery mechanism using NO-dielectric barrier discharge (DBD) plasma that can generate and transport NO with controlled concentration to the area of interest to regulate osteoprogenitor cell activity. We built a non-thermal atmospheric pressure DBD plasma nozzle system based on our previously published design and similar designs in the literature. The electrical and spectral analyses demonstrated that N2 dissociated into NO under typical DBD voltage-current characteristics. We treated osteoprogenitor cells (MC3T3-E1) using NO-plasma treatment system. Our results demonstrated that we could control NO concentration within cell culture media and could introduce NO into the intracellular space using NO-plasma treatment with various treatment times. We confirmed that NO-plasma treatment maintained cell viability and did not create any toxicity even with prolonged treatment durations. Finally, we demonstrated that NO-plasma treatment induced early osteogenic differentiation in the absence of pro-osteogenic growth factors/proteins. These findings suggest that through the NO-plasma treatment system we are able to generate and transport tissue-specific amounts of NO to an area of interest to mediate osteoprogenitor cell activity without subsequent toxicity. This opens up the possibility to develop DBD plasma-assisted tissue-specific NO delivery strategies for therapeutic intervention in the prevention and treatment of bone diseases.

  10. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    SciTech Connect

    Bag, Swarnendu; Banerjee, Deb Ranjan; Basak, Amit; Das, Amit Kumar; Pal, Mousumi; Banerjee, Rita; Paul, Ranjan Rashmi; Chatterjee, Jyotirmoy

    2015-04-17

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

  11. Expression of prion protein is closely associated with pathological and clinical progression and abnormalities of p53 in head and neck squamous cell carcinomas.

    PubMed

    Wei, Wei; Shi, Qi; Zhang, Nai-Song; Xiao, Kang; Chen, Li-Na; Yang, Xiao-Dong; Ji, Jia-Fu; Dong, Xiao-Ping

    2016-02-01

    Prion protein (PrP) is a glycosyl-phosphatidylinositol (GPI)-anchored membrane protein that functions as a unique pathogenic agent in transmissible spongiform encephalopathy (TSE). In the past decade, overexpression of PrP was observed in a number of human malignant tumors, such as gastric, breast and pancreatic cancer. However, the role of PrP expression in squamous cell carcinoma is rarely documented. To screen PrP expression in head and neck squamous cell carcinoma (HNSCCs), the paraffin-embedded specimens of 92 pathologically diagnosed HNSCCs were assessed by PrP-specific immunohistochemistry (IHC). A total of 55.43% (51/92) of the tested carcinoma tissues were PrP-positive. The rate of positivity and the staining intensity of PrP were closely related with the pathological degree of the HNSCCs; a higher rate of PrP expression was noted in the group of poorly differentiated cancers. PrP-positivity rates increased along with the progression of the clinical grade of the carcinomas. Further evaluation of the associations between PrP expression and the data concerning p53 abnormalities and human papillomavirus (HPV) infection in these samples as previously described, revealed that PrP-positive staining was more frequently detected in the tissues with p53-positive accumulation and the wild-type TP53 gene. The patients with a proline (Pro) polymorphism in SNP72 of TP53 showed significantly higher PrP-positive rates than those with arginine (Arg). No notable difference in PrP expression was identified between the HPV-positive and HPV-negative group. These data indicate a close association of PrP expression with clinical and histological differentiation of HNSCCs, as well as abnormalities of p53. PMID:26718886

  12. Induction of mitotic and chromosomal abnormalities on Allium cepa cells by pesticides imidacloprid and sulfentrazone and the mixture of them.

    PubMed

    Bianchi, Jaqueline; Fernandes, Thais Cristina Casimiro; Marin-Morales, Maria Aparecida

    2016-02-01

    To evaluate the cytotoxic and genotoxic effects of low concentrations of pesticides in non-target organisms, seeds of Allium cepa were exposed for 24 h to the imidacloprid insecticide, sulfentrazone herbicide and to the mixture of them, followed by recovery periods of 48 and 72 h. Imidacloprid results indicated an indirect genotoxic effect by inducing different types of chromosome aberration (CA), mainly bridges and chromosomal adherences. Cells with micronucleus (MN) were not significant in the analyzed meristems. Moreover, the 72-h recovery tests indicated that the two lower concentrations of the insecticide (0.036 and 0.36 g L(-1)) had their genotoxic effects minimized after discontinuation of treatment, differently to the observed for the field concentration (3.6 g L(-1)). Sulfentrazone herbicide at field concentration (6 g L(-1)) caused cytotoxic effects by inducing nuclear fragmentation and inhibition of cell division. The other concentrations (0.06, 0.6 and 1.2 g L(-1)) indicated genotoxic effects for this herbicide. The concentration of 0.06 g L(-1) induced persistent effects that could be visualized both by the induction of CA in the recovery times as by the presence of MN in meristematic and F1 cells. The induction of MN by this lowest concentration was associated with the great amount of breakage, losses and chromosomal bridges. The mixture of pesticides induced genotoxic and cytotoxic effects, by reducing the MI of the cells. The chromosomal damage induced by the mixture of pesticides was not persistent to the cells, since such damage was minimized 72 h after the interruption of the exposure. PMID:26386773

  13. Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response

    PubMed Central

    Fernández, Tahia D.; Gómez, Enrique; Doña, Inmaculada; Campo, Paloma; Rondon, Carmen; Gonzalez, Miguel; Gomez, Francisca; Palomares, Francisca; Salas, Maria; Blanca, Miguel; Mayorga, Cristobalina; Torres, Maria J.

    2015-01-01

    Allergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to control its symptoms, however, up to 30% of patients may not respond. Previous studies of the immunological mechanisms involved in allergen-immunotherapy (AIT) have focused on the humoral and T-cell response and several studies have evaluated some B-cell subpopulations during AIT and their role in immunological tolerance. However, although B and plasma-cell subpopulations are two of the most important cellular subtypes involved in allergic reactions, their relation with AIT efficacy remains unelucidated. The objective was to analyze the effects of immunotherapy on different B and plasma-cell subpopulations and whether these changes correlate with the clinical response to the treatment. Although no changes are found in B-cell subpopulations, responder patients show increased levels of memory B-cells even before the beginning of treatment. Changes in plasma-cell subpopulations are found, mainly in circulating inflammatory plasma-cells that could affect the response to the allergen. Moreover, an early increase of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the determination of the memory B-cells before the initiation of the treatment, and the quantification of IgG4 and IgG4-secreting-cells in the first months of immunotherapy, could serve as markers for the clinical response to treatment. PMID:26416023

  14. Phase imaging microscopy for the diagnostics of plasma-cell interaction

    NASA Astrophysics Data System (ADS)

    Ohene, Yolanda; Marinov, Ilya; de Laulanié, Lucie; Dupuy, Corinne; Wattelier, Benoit; Starikovskaia, Svetlana

    2015-06-01

    Phase images of biological specimens were obtained by the method of Quadriwave Lateral Shearing Interferometry (QWLSI). The QWLSI technique produces, at high resolution, phase images of the cells having been exposed to a plasma treatment and enables the quantitative analysis of the changes in the surface area of the cells over time. Morphological changes in the HTori normal thyroid cells were demonstrated using this method. There was a comparison of the cell behaviour between control cells, cells treated by plasma of a nanosecond dielectric barrier discharge, including cells pre-treated by catalase, and cells treated with an equivalent amount of H2O2. The major changes in the cell membrane morphology were observed at only 5 min after the plasma treatment. The primary role of reactive oxygen species (ROS) in this degradation is suggested. Deformation and condensation of the cell nucleus were observed 2-3 h after the treatment and are supposedly related to apoptosis induction. The coupling of the phase QWLSI with immunofluorescence imaging would give a deeper insight into the mechanisms of plasma induced cell death.

  15. Interaction of cold plasmas with biological cells: What we have learned so far

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir

    2006-10-01

    In the last two decades, non-equilibrium, low temperature, atmospheric pressure plasmas have gained acceptance as an attractive technological solution in industrial applications such as the surface modification of polymers and the cleaning of flue gases. As more reliable ``cold'' plasma sources are developed, new and interesting applications continue to emerge. Amongst the more recent applications, the use of atmospheric pressure cold plasmas in the biomedical field is presently experiencing a heightened interest from the plasma science research community. This is due to promising possibilities to use these plasmas in medical research such as wound healing, tissue engineering, surface modification of biocompatible materials, and the sterilization of reusable heat-sensitive medical instruments. However, before any of these exciting possibilities become reality, an in-depth understanding of the effects of plasma on the cellular and sub-cellular levels has to be achieved. In this paper, a review of the knowledge that has been gained during the last few years will be presented. First an overview of research efforts on the inactivation of bacterial cells will be presented. This includes the evaluation of the inactivation kinetics and the roles played by the various plasma agents (such as UV photons and free radicals) in the inactivation process. In the second part of this talk, plasma sub-lethal effects on both prokaryotic and eukaryotic cells will be discussed. Finally, the prospects of the use of ``cold'' plasmas in the biomedical field are outlined.

  16. [Renal abnormalities in HIV infected patients].

    PubMed

    Pernasetti, María Marta; Chiurchiu, Carlos; Fuente, Jorge de la; Arteaga, Javier de; Douthat, Walter; Bardosy, Cecilia; Zarate, Abel; Massari, Pablo U

    2010-01-01

    Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious agents and/or drugs. Little is known about the prevalence of renal diseases that may occur as a complication of or related to HIV infection in asymptomatic patients. This is a single center cross-sectional study of asymptomatic HIV(+) patients referred to a nefrology care service at an Argentine hospital to look for the presence of renal abnormalities. Fifty two consecutive patients were studied between April and November 2008. Patients underwent plasma and urine analysis, ultrasound, and kidney biopsy as needed. Mean age was 39.9 +/- 10.6 years, 88% were male, time from HIV diagnosis 53.2 +/- 41.2 months (2-127); 71% had HIV-disease and 77% were on antiretroviral therapy. Mean plasma HIV-RNA copies number was 7.043 +/- 3.322 and CD4+ cell count: 484 +/- 39. Pathologic findings in urine analysis were present in 30.7% of patients: albuminuria 16.6%, microscopic hematuria 11.5%, hypercalciuria 10.8% and crystalluria 6%. Mean glomerular filtration rate was 102.2 +/- 22.95 ml/min (34-149) and 41% of patients could be classified in stages 1 to 3 of chronic kidney disease. Renal abnormalities prevaled in older patients without relationship with presence of HIV-disease. Two patients were biopsied and the findings included: tubulointerstitial nephritis with presence of crystal deposition in one and IgA nephropathy in the other. No HIV-associated nephropathy was detected. The broad spectrum and the high prevalence of lesions found in this series suggest that asymptomatic HIV-infected patients should routinely undergo renal evaluation. PMID:20529774

  17. Multiple plasma cell granulomas of the larynx in a young man.

    PubMed

    Shires, Courtney; Samant, Sandeep

    2014-03-01

    Plasma cell granuloma of the larynx is a rare benign lesion of unknown etiology, with only 21 cases reported previously. We report an additional case of plasma cell granuloma in which a 26-year-old man experienced a 1.5 × 3.4-cm, completely obstructing subglottic lesion. Because of the patient's young age, history of hemoptysis, bleeding from his tracheostomy, and the rarity of plasma cell granulomas, the patient was assumed to have hemangioma until proven otherwise. He presented with a partially obstructing glottic lesion 4 months later. Both the subglottic and glottic lesions were excised endoscopically. Multiple modalities have been used to treat plasma cell granulomas, including radiation, endoscopic CO2 laser ablation, high-dose prednisone, and open excision. In our case, steroids were given in the interim between the 2 excisions. This is the first report of a patient with two laryngeal plasma cell granulomas and the 22nd reported case of laryngeal plasma cell granuloma. PMID:24652567

  18. Application of atmospheric plasma sources in growth and differentiation of plant and mammalian stem cells

    NASA Astrophysics Data System (ADS)

    Puac, Nevena

    2014-10-01

    The expansion of the plasma medicine and its demand for in-vivo treatments resulted in fast development of various plasma devices that operate at atmospheric pressure. These sources have to fulfill all demands for application on biological samples. One of the sources that meet all the requirements needed for treatment of biological material is plasma needle. Previously, we have used this device for sterilization of planctonic samples of bacteria, MRSA biofilm, for improved differentiation of human periodontal stem cells into osteogenic line and for treatment of plant meristematic cells. It is well known that plasma generates reactive oxygen species (ROS) and reactive nitrogen species (RNS) that strongly affect metabolism of living cells. One of the open issues is to correlate external plasma products (electrons, ions, RNS, ROS, photons, strong fields etc.) with the immediate internal response which triggers or induces effects in the living cell. For that purpose we have studied the kinetics of enzymes which are typical indicators of the identity of reactive species from the plasma created environment that can trigger signal transduction in the cell and ensue cell activity. In collaboration with Suzana Zivkovicm, Institute for Biological Research ``Sinisa Stankovic,'' University of Belgrade; Nenad Selakovic, Institute of Physics, University of Belgrade; Milica Milutinovic, Jelena Boljevic, Institute for Biological Research ``Sinisa Stankovic,'' University of Belgrade; and Gordana Malovic, Zoran Lj. Petrovic, Institute of Physics, University of Belgrade. Grants III41011, ON171037 and ON173024, MESTD, Serbia.

  19. The relation between doses or post-plasma time points and apoptosis of leukemia cells induced by dielectric barrier discharge plasma

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Zhang, Haixia; Xue, Zhixiao; Yin, Huijuan; Niu, Qing; Chen, Hongli

    2015-12-01

    The dielectric barrier discharge (DBD) plasma was applied to induce apoptosis of LT-12 leukemia cells. Plasma effects on cell death was evaluated by MTT assay and FCM apoptosis assay with Annexin V/PI double staining, suggesting that plasma killing cells rate and inducing cell apoptosis rate both positively were related to the plasma doses or the post-plasma time points. The cell death rates increased from 15.2% to 33.1% and the apoptosis rate raise from 23.8% to 28% when the dose raise from 60s to 120 s at 8 h post-plasma, while they increased from 15.4% to 34.9% and from 48% to 55.3% respectively at the same doses at 12 h post-plasma. Furthermore, the production of reactive oxygen species (ROS), gene and protein expression for Caspases and Bcl-2 family members were measured for exploring the related apoptotic mechanisms phenomenon. We found ROS immediately increased to 1.24 times of the original amount, then increasing to 5.39-fold at 20 h after treatment. The gene and protein expression for Caspases and Bcl-2 family members are very active at 8-12 h post-plasma. Our results demonstrate that DBD plasma can effectively induce tumor cell death through primarily related apoptotic mechanisms.

  20. Plasma-on-chip device for stable irradiation of cells cultured in media with a low-temperature atmospheric pressure plasma.

    PubMed

    Okada, Tomohiro; Chang, Chun-Yao; Kobayashi, Mime; Shimizu, Tetsuji; Sasaki, Minoru; Kumagai, Shinya

    2016-09-01

    We have developed a micro electromechanical systems (MEMS) device which enables plasma treatment for cells cultured in media. The device, referred to as the plasma-on-chip, comprises microwells and microplasma sources fabricated together in a single chip. The microwells have through-holes between the microwells and microplasma sources. Each microplasma source is located on the backside of each microwells. The reactive components generated by the microplasma sources pass through the through-holes and reach cells cultured in the microwells. In this study, a plasma-on-chip device was modified for a stable plasma treatment. The use of a dielectric barrier discharge (DBD) technique allowed a stable plasma treatment up to 3 min. The plasma-on-chip with the original electrode configuration typically had the maximum stable operation time of around 1 min. Spectral analysis of the plasma identified reactive species such as O and OH radicals that can affect the activity of cells. Plasma treatment was successfully performed on yeast (Saccharomyces cerevisiae) and green algae (Chlorella) cells. While no apparent change was observed with yeast, the treatment degraded the activity of the Chlorella cells and decreased their fluorescence. The device has the potential to help understand interactions between plasma and cells. PMID:27059851

  1. Syntaxin-4 is essential for IgE secretion by plasma cells

    SciTech Connect

    Rahman, Arman; DeCourcey, Joseph; Larbi, Nadia Ben; Loughran, Sinéad T.; Walls, Dermot; Loscher, Christine E.

    2013-10-11

    Highlights: •Knock-down of syntaxin-4 in U266 plasma cells resulted in reduction of IgE secretion. •Knock-down of syntaxin-4 also leads to the accumulation of IgE in the cell. •Immuno-fluorescence staining shows co-localisation of IgE and syntaxin-4 in U266 cells. •Findings suggest a critical requirement for syntaxin-4 in IgE secretion from plasma cells. -- Abstract: The humoral immune system provides a crucial first defense against the invasion of microbial pathogens via the secretion of antigen specific immunoglobulins (Ig). The secretion of Ig is carried out by terminally differentiated B-lymphocytes called plasma cells. Despite the key role of plasma cells in the immune response, the mechanisms by which they constitutively traffic large volumes of Ig out of the cell is poorly understood. The involvement of Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in the regulation of protein trafficking from cells has been well documented. Syntaxin-4, a member of the Qa SNARE syntaxin family has been implicated in fusion events at the plasma membrane in a number of cells in the immune system. In this work we show that knock-down of syntaxin-4 in the multiple myeloma U266 human plasma cell line results in a loss of IgE secretion and accumulation of IgE within the cells. Furthermore, we show that IgE co-localises with syntaxin-4 in U266 plasma cells suggesting direct involvement in secretion at the plasma membrane. This study demonstrates that syntaxin-4 plays a critical role in the secretion of IgE from plasma cells and sheds some light on the mechanisms by which these cells constitutively traffic vesicles to the surface for secretion. An understanding of this machinery may be beneficial in identifying potential therapeutic targets in multiple myeloma and autoimmune disease where over-production of Ig leads to severe pathology in patients.

  2. Silicon solar cells made by a self-aligned, selective-emitter, plasma-etchback process

    DOEpatents

    Ruby, D.S.; Schubert, W.K.; Gee, J.M.

    1999-02-16

    A potentially low-cost process for forming and passivating a selective emitter. The process uses a plasma etch of the heavily doped emitter to improve its performance. The grids of the solar cell are used to mask the plasma etch so that only the emitter in the region between the grids is etched, while the region beneath the grids remains heavily doped for low contact resistance. This process is potentially low-cost because it requires no alignment. After the emitter etch, a silicon nitride layer is deposited by plasma-enhanced, chemical vapor deposition, and the solar cell is annealed in a forming gas. 5 figs.

  3. Silicon solar cells made by a self-aligned, selective-emitter, plasma-etchback process

    DOEpatents

    Ruby, Douglas S.; Schubert, William K.; Gee, James M.

    1999-01-01

    A potentially low-cost process for forming and passivating a selective emitter. The process uses a plasma etch of the heavily doped emitter to improve its performance. The grids of the solar cell are used to mask the plasma etch so that only the emitter in the region between the grids is etched, while the region beneath the grids remains heavily doped for low contact resistance. This process is potentially low-cost because it requires no alignment. After the emitter etch, a silicon nitride layer is deposited by plasma-enhanced, chemical vapor deposition, and the solar cell is annealed in a forming gas.

  4. An evaluation of anti-oxidative protection for cells against atmospheric pressure cold plasma treatment

    SciTech Connect

    Ma Ruonan; Zhang Qian; Feng Hongqing; Liang Yongdong; Li Fangting; Zhu Weidong; Zhang Jue; Fang Jing; Becker, Kurt H.

    2012-03-19

    With the development of plasma medicine, safety issues are emerging as a serious concern. In this study, both intracellular (genetic engineering) and extracellular (scavengers) measures were tested in an effort to determine the best protection for cells against plasma-induced oxidative stress. All results of immediate reactive species detection, short term survival and long term proliferation, suggest that intracellular pathways are superior in reducing oxidative stress and cell death. This work provides a potential mechanism to enhance safety and identifies precautionary measures that should be taken in future clinical applications of plasmas.

  5. Effect of plasma membrane fluidity on serotonin transport by endothelial cells

    SciTech Connect

    Block, E.R.; Edwards, D. )

    1987-11-01

    To evaluate the effect of plasma membrane fluidity of lung endothelial cells on serotonin transport, porcine pulmonary artery endothelial cells were incubated for 3 h with either 0.1 mM cholesterol hemisuccinate, 0.1 mM cis-vaccenic acid, or vehicle (control), after which plasma membrane fluidity and serotinin transport were measured. Fluorescence spectroscopy was used to measure fluidity in the plasma membrane. Serotonin uptake was calculated from the disappearance of ({sup 14}C)-serotonin from the culture medium. Cholesterol decreased fluidity in the subpolar head group and central and midacyl side-chain regions of the plasma membrane and decreased serotonin transport, whereas cis-vaccenic acid increased fluidity in the central and midacyl side-chain regions of the plasma membrane and also increased serotonin transport. Cis-vaccenic acid had no effect of fluidity in the subpolar head group region of the plasma membrane. These results provide evidence that the physical state of the central and midacyl chains within the pulmonary artery endothelial cell plasma membrane lipid bilayer modulates transmembrane transport of serotonin by these cells.

  6. Mechanisms of interaction of non-thermal plasma with living cells

    NASA Astrophysics Data System (ADS)

    Kalghatgi, Sameer Ulhas

    Thermal plasmas and lasers have been widely used in medicine to cut, ablate and cauterize tissues through heating; in contrast, non-thermal plasma produces various highly active molecules and atoms without heat. As a result, its effects on living cells and tissues could be selective and tunable. This makes non-thermal plasma very attractive for medical applications. However, despite several interesting demonstrations of non-thermal plasma in blood coagulation and tissue sterilization, the biological and physical mechanisms of its interaction with living cells are still poorly understood impeding further development of non-thermal plasma as a clinical tool. Although several possible mechanisms of interaction have been suggested, no systematic experimental work has been performed to verify these hypotheses. Using cells in culture, it is shown in this work that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects ranging from increasing cell proliferation to inducing apoptosis which are consistent with the effects of oxidative stress. DNA damage is chosen as a marker to assess the effects of oxidative stress in a quantitative manner. It is demonstrated here that plasma induced DNA damage as well as other effects ranging from cell proliferation to apoptosis are indeed due to production of intracellular reactive oxygen species (ROS). We found that DNA damage is initiated primarily by plasma generated active neutral species which cannot be attributed to ozone alone. Moreover, it is found that extracellular media and its components play a critical role in the transfer of the non-thermal plasma initiated oxidative stress into cells. Specifically, it is found that the peroxidation efficiency of amino acids is the sole predictor of the ability of the medium to transfer the oxidative stress induced by non-thermal plasma. Phosphorylation of H2AX, a DNA damage marker, following plasma treatment is found to be ATR dependent and ATM

  7. Factors Regulating Immunoglobulin Production by Normal and Disease-Associated Plasma Cells

    PubMed Central

    Jackson, David A.; Elsawa, Sherine F.

    2015-01-01

    Immunoglobulins are molecules produced by activated B cells and plasma cells in response to exposure to antigens. Upon antigen exposure, these molecules are secreted allowing the immune system to recognize and effectively respond to a myriad of pathogens. Immunoglobulin or antibody secreting cells are the mature form of B lymphocytes, which during their development undergo gene rearrangements and selection in the bone marrow ultimately leading to the generation of B cells, each expressing a single antigen-specific receptor/immunoglobulin molecule. Each individual immunoglobulin molecule has an affinity for a unique motif, or epitope, found on a given antigen. When presented with an antigen, activated B cells differentiate into either plasma cells (which secrete large amounts of antibody that is specific for the inducing antigen), or memory B cells (which are long-lived and elicit a stronger and faster response if the host is re-exposed to the same antigen). The secreted form of immunoglobulin, when bound to an antigen, serves as an effector molecule that directs other cells of the immune system to facilitate the neutralization of soluble antigen or the eradication of the antigen-expressing pathogen. This review will focus on the regulation of secreted immunoglobulin by long-lived normal or disease-associated plasma cells. Specifically, the focus will be on signaling and transcriptional events that regulate the development and homeostasis of long-lived immunoglobulin secreting plasma cells. PMID:25615546

  8. Red cell volume with changes in plasma osmolarity during maximal exercise.

    NASA Technical Reports Server (NTRS)

    Van Beaumont, W.

    1973-01-01

    The volume of the red cell in vivo was measured during acute changes in plasma osmolarity evoked through short (6 to 8 min) maximal exercise in six male volunteer subjects. Simultaneous measurements of mean corpuscular red cell volume (MCV), hematocrit, blood hemoglobin, mean corpuscular hemoglobin concentration (MCHC), and plasma osmolarity showed that there was no change in the MCV or MCHC with a concomitant rise of nearly 6% in plasma osmolarity. Apparently, in vivo, the volume of the red cell in exercising healthy human subjects does not change measurably, in spite of significant changes in osmotic pressure of the surrounding medium. Consequently, it is not justified to correct postexercise hematocrit measurements for changes in plasma osmolarity.

  9. Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets

    PubMed Central

    Prada, Ilaria; Meldolesi, Jacopo

    2016-01-01

    Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated. PMID:27517914

  10. Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets.

    PubMed

    Prada, Ilaria; Meldolesi, Jacopo

    2016-01-01

    Exosomes and ectosomes, extracellular vesicles of two types generated by all cells at multivesicular bodies and the plasma membrane, respectively, play critical roles in physiology and pathology. A key mechanism of their function, analogous for both types of vesicles, is the fusion of their membrane to the plasma membrane of specific target cells, followed by discharge to the cytoplasm of their luminal cargo containing proteins, RNAs, and DNA. Here we summarize the present knowledge about the interactions, binding and fusions of vesicles with the cell plasma membrane. The sequence initiates with dynamic interactions, during which vesicles roll over the plasma membrane, followed by the binding of specific membrane proteins to their cell receptors. Membrane binding is then converted rapidly into fusion by mechanisms analogous to those of retroviruses. Specifically, proteins of the extracellular vesicle membranes are structurally rearranged, and their hydrophobic sequences insert into the target cell plasma membrane which undergoes lipid reorganization, protein restructuring and membrane dimpling. Single fusions are not the only process of vesicle/cell interactions. Upon intracellular reassembly of their luminal cargoes, vesicles can be regenerated, released and fused horizontally to other target cells. Fusions of extracellular vesicles are relevant also for specific therapy processes, now intensely investigated. PMID:27517914

  11. Structural Rearrangements in CHO Cells After Disruption of Individual Cytoskeletal Elements and Plasma Membrane.

    PubMed

    Jokhadar, Špela Zemljič; Derganc, Jure

    2015-04-01

    Cellular structural integrity is provided primarily by the cytoskeleton, which comprises microtubules, actin filaments, and intermediate filaments. The plasma membrane has been also recognized as a mediator of physical forces, yet its contribution to the structural integrity of the cell as a whole is less clear. In order to investigate the relationship between the plasma membrane and the cytoskeleton, we selectively disrupted the plasma membrane and each of the cytoskeletal elements in Chinese hamster ovary cells and assessed subsequent changes in cellular structural integrity. Confocal microscopy was used to visualize cytoskeletal rearrangements, and optical tweezers were utilized to quantify membrane tether extraction. We found that cholesterol depletion from the plasma membrane resulted in rearrangements of all cytoskeletal elements. Conversely, the state of the plasma membrane, as assessed by tether extraction, was affected by disruption of any of the cytoskeletal elements, including microtubules and intermediate filaments, which are located mainly in the cell interior. The results demonstrate that, besides the cytoskeleton, the plasma membrane is an important contributor to cellular integrity, possibly by acting as an essential framework for cytoskeletal anchoring. In agreement with the tensegrity model of cell mechanics, our results support the notion of the cell as a prestressed structure. PMID:25395197

  12. Plasma functionalization of poly(vinyl alcohol) hydrogel for cell adhesion enhancement

    PubMed Central

    Ino, Julia M.; Chevallier, Pascale; Letourneur, Didier; Mantovani, Diego; Le Visage, Catherine

    2013-01-01

    Tailoring the interface interactions between a biomaterial and the surrounding tissue is a capital aspect to consider for the design of medical devices. Poly(vinyl alcohol) (PVA) hydrogels present suitable mechanical properties for various biological substitutes, however the lack of cell adhesion on their surface is often a problem. The common approach is to incorporate biomolecules, either by blending or coupling. But these modifications disrupt PVA intra- and intermolecular interactions leading therefore to a loss of its original mechanical properties. In this work, surface modification by glow discharge plasma, technique known to modify only the surface without altering the bulk properties, has been investigated to promote cell attachment on PVA substrates. N2/H2 microwave plasma treatment has been performed, and the chemical composition of PVA surface has been investigated. X-ray photoelectron and Fourier transform infrared analyses on the plasma-treated films revealed the presence of carbonyl and nitrogen species, including amine and amide groups, while the main structure of PVA was unchanged. Plasma modification induced an increase in the PVA surface wettability with no significant change in surface roughness. In contrast to untreated PVA, plasma-modified films allowed successful culture of mouse fibroblasts and human endothelial cells. These results evidenced that the grafting was stable after rehydration and that it displayed cell adhesive properties. Thus plasma amination of PVA is a promising approach to improve cell behavior on contact with synthetic hydrogels for tissue engineering. PMID:23989063

  13. Enhanced cell adhesion to silicone implant material through plasma surface modification.

    PubMed

    Hauser, J; Zietlow, J; Köller, M; Esenwein, S A; Halfmann, H; Awakowicz, P; Steinau, H U

    2009-12-01

    Silicone implant material is widely used in the field of plastic surgery. Despite its benefits the lack of biocompatibility this material still represents a major problem. Due to the surface characteristics of silicone, protein adsorption and cell adhesion on this polymeric material is rather low. The aim of this study was to create a stable collagen I surface coating on silicone implants via glow-discharge plasma treatment in order to enhance cell affinity and biocompatibility of the material. Non-plasma treated, collagen coated and conventional silicone samples (non-plasma treated, non-coated) served as controls. After plasma treatment the change of surface free energy was evaluated by drop-shape analysis. The quality of the collagen coating was analysed by electron microscopy and Time-Of-Flight Secondary Ion Mass Spectrometry. For biocompatibility tests mouse fibroblasts 3T3 were cultivated on the different silicone surfaces and stained with calcein-AM and propidium iodine to evaluate cell viability and adherence. Analysis of the different surfaces revealed a significant increase in surface free energy after plasma pre-treatment. As a consequence, collagen coating could only be achieved on the plasma activated silicone samples. The in vitro tests showed that the collagen coating led to a significant increase in cell adhesion and cell viability. PMID:19641852

  14. Abnormal increase of neuronal precursor cells and exacerbated neuroinflammation in the corpus callosum in murine model of systemic lupus erythematosus

    PubMed Central

    Leung, Joseph Wai-Hin; Lau, Benson Wui-Man; Chan, Vera Sau-Fong; Lau, Chak-Sing; So, Kwok-Fai

    2016-01-01

    Purpose: Systemic Lupus Erythematosus (SLE) is an autoimmune disease which is characterised by elevated levels of autoantibodies and cytokines in the body. Via alteration of the regulation of inflammation, damage to different organ systems, including the central nervous system (CNS), was found in SLE patients. Patients diagnosed with SLE were reported to suffer from different kinds of psychiatric signs and symptoms. As neurogenesis has been suggested to be a potential key player of psychiatric symptoms and emotional behavior disturbances, this study aims to investigate whether neurogenesis is altered in an animal model of SLE. Also, neuroinflammation was studied. Methods: Female NZB/W F1 mice were used as an animal model of SLE. Animals were divided into two groups: 1. pre-diseased mice (lupus-prone NZB/W F1 female mice, age 10–15 weeks, negative for proteinuria and with basal levels of serum anti-dsDNA autoantibodies) and 2. diseased mice (NZB/W F1 female mice, > 25 weeks of age, with elevated serum levels of anti-dsDNA autoantibodies and with persistent proteinuria of > 3 mg/ml for more than 2 weeks). Comparisons of the levels of neurogenesis and neuroinflammtion between two groups of mice were studied by the immunohistochemistry. Results: After the onset of SLE symptoms, a reduction of neurogenesis in the hippocampus was found, while there was a dramatic increase of doublecortin (DCX+) neuronal precursor cells in the corpus callosum (CC) and in the subventricular zone (SVZ). Meanwhile, exacerbated inflammation was present in the corpus callosum of the diseased mice, which was suggested by the increased number of GFAP+ cells and IBA-1+ cells. Conclusions: To the best of our knowledge, this is the first study showing an increase of neuronal precursor cells in the corpus callosum of the female NZB/W F1 mice. The present study suggests a coincidence but not a causal relationship between neurogenesis and neuroinflammation. The present results have

  15. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  16. An Adult Male Presenting with Concurrent Plasma Cell Myeloma Involving a CCND1-IGH Translocation and Chronic Myelogenous Leukemia with a Variant (9;22) Translocation.

    PubMed

    Lee, Peter M; Siangchin, Ken; Song, Sophie; Shabsovich, David; Naeini, Yalda; Tirado, Carlos A

    2016-01-01

    The t(11;14)(q13;q32) involving IGH and CCND1 a nd t(9;22) (q34;q11.2) involving BCR and ABL1 are common abnormalities in plasma cell myeloma (PCM) and chronic myelogenous leukemia (CML), respectively. However, the concurrence of the two malignancies is extremely rare. Herein, we present a case of an 87-year-old male who presented with anemia and monocytosis. FISH studies on a bone marrow sample enriched for plasma cells detected a t(11;14) positive for IGH and CCND1 fusion in 92% of nuclei. However, cytogenetic analysis of the bone marrow revealed a t(9;22)(q34;q11.2) in 40% of the metaphases. Interphase and metaphase FISH studies on the sample confirmed the presence of the BCR-ABL1 fusion in 88% of nuclei but did not show any signals corresponding to the derivative 9, suggesting a variant t(9;22) with a deletion or additional material of unknown origin at the 9q34 band of the derivative 9 and a derivative 22 bearing the BCR-ABL1 fusion gene. The concurrence of plasma cell myeloma and chronic myelogenous leukemia is extremely rare with less than 20 cases reported. The molecular pathway in which the multiple malignancies arise is still poorly understood, and this case provides insight into the concurrence of PCM and CML. PMID:27584682

  17. Negative regulation of erythroblast maturation by Fas-L(+)/TRAIL(+) highly malignant plasma cells: a major pathogenetic mechanism of anemia in multiple myeloma.

    PubMed

    Silvestris, Franco; Cafforio, Paola; Tucci, Marco; Dammacco, Franco

    2002-02-15

    Multiple myeloma (MM) is associated with severe normochromic/normocytic anemia. This study demonstrates that the abnormal up-regulation of apoptogenic receptors, including both Fas ligand (L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), by highly malignant myeloma cells is involved in the pathogenesis of the ineffective erythropoiesis and chronic exhaustion of the erythroid matrix. By measuring Fas-L and TRAIL in plasma cells and the content of glycophorin A (GpA) in erythroblasts from a cohort of 28 untreated, newly diagnosed patients with MM and 7 with monoclonal gammopathy of undetermined significance (MGUS), selected in relation to their peripheral hemoglobin values, results showed that both receptors occurred at high levels in 15 severely anemic MM patients. Their marrow erythropoietic component was low and included predominantly immature GpA(+dim) erythroblasts, in contrast with the higher relative numbers of mature GpA(+bright) erythroid cells observed in the nonanemic patients and those with MGUS. In cocultures with autologous Fas-L(+)/TRAIL(+) myeloma cells, the expanded GpA(+dim) erythroid population underwent prompt apoptosis after direct exposure to malignant plasma cells, whereas erythroblasts from nonanemic patients were scarcely affected. The evidence that Fas-L(+)/TRAIL(+) malignant plasma cells prime erythroblast apoptosis by direct cytotoxicity was also supported by the increase of FLICE in fresh immature GpA(+dim) erythroid cells, whereas ICE and caspase-10 increased in subsequent maturative forms. In addition, GATA-1, a survival factor for erythroid precursors, was remarkably down-regulated in fresh erythroblasts from the severely anemic patients. These results indicate that progressive destruction of the erythroid matrix in aggressive MM is due to cytotoxic mechanisms based on the up-regulation in myeloma cells of Fas-L, TRAIL, or both. It is conceivable that the altered regulation of these receptors defines a peculiar

  18. Genital Chlamydia trachomatis infections in patients with abnormal cervical smears: effect of tetracycline treatment on cell changes.

    PubMed

    Mecsei, R; Haugen, O A; Halvorsen, L E; Dalen, A

    1989-03-01

    A group of 1760 women aged 14-35 years were examined for the concurrent presence of Chlamydia trachomatis and cellular atypia of cervical smears. Positive tests for C trachomatis were found in 126 women (7.2%). Cell changes were found in 85 women (4.8%), and 25 of these were C trachomatis-positive. Slight cellular atypia was the major finding in the smears from 22 of the C trachomatis-positive women, whereas three patients had more pronounced cell changes. Smears reverted to normal in 18 of the 23 patients who returned for tetracycline treatment and follow-up cytology. All 18 patients had smears showing slight cellular atypia prior to therapy. In five patients who also had cellular changes suggesting a human papillomavirus infection, the smears did not revert to normal after antibiotic therapy during the observation period. These findings suggest that patients with C trachomatis and mild cellular atypia should have antibiotic therapy and repeat smears taken before further treatment is considered. More advanced cellular atypia is unlikely to be caused by C trachomatis. PMID:2915857

  19. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells

    PubMed Central

    Park, Sung-Bin; Kim, Byungtak; Bae, Hansol; Lee, Hyunkyung; Lee, Seungyeon; Choi, Eun H.; Kim, Sun Jung

    2015-01-01

    Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05) by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified “cellular movement, connective tissue development and function, tissue development” and “cell-to-cell signaling and interaction, cell death and survival, cellular development” as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option. PMID:26042423

  20. Plasma engineering models of tandem mirror devices with high-field test-cell inserts

    SciTech Connect

    Fenstermacher, M.E.; Campbell, R.B.

    1985-04-03

    Plasma physics and engineering models of tandem mirror devices operated with a high-field technology test-cell insert in the central cell, which have been incorporated recently in the TMRBAR tandem mirror reactor physics code, are described. The models include particle and energy balance in the test-cell region as well as the interactions between the test-cell particles and those flowing through the entire device. The code calculations yield consistent operating parameters for the test-cell, central cell, and end cell systems. A benchmark case for the MFTF-..cap alpha..+T configuration is presented which shows good agreement between the code results and previous calculations.

  1. Molecular Phenotyping of Immune Cells from Young NOD Mice Reveals Abnormal Metabolic Pathways in the Early Induction Phase of Autoimmune Diabetes

    PubMed Central

    Wu, Jian; Kakoola, Dorothy N.; Lenchik, Nataliya I.; Desiderio, Dominic M.; Marshall, Dana R.; Gerling, Ivan C.

    2012-01-01

    Islet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse – a model for human type 1 diabetes (T1D). The molecular events that lead to insulitis and initiate autoimmune diabetes are poorly understood. Since TID is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease. We evaluated the molecular phenotype (mRNA and protein expression) and molecular networks of ex vivo unfractionated spleen leukocytes from 2 and 4 week-old NOD mice in comparison to two control strains. Analysis of the global gene expression profiles and hierarchical clustering revealed that the majority (∼90%) of the differentially expressed genes in NOD mice were repressed. Furthermore, analysis using a modern suite of multiple bioinformatics approaches identified abnormal molecular pathways that can be divided broadly into 2 categories: metabolic pathways, which were predominant at 2 weeks, and immune response pathways, which were predominant at 4 weeks. Network analysis by Ingenuity pathway analysis identified key genes/molecules that may play a role in regulating these pathways. These included five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). Based on the literature, genes that may play a role in regulating metabolic pathways at 2 weeks include Myc and HNF4A, and at 4 weeks, beta-estradiol, p53, Akt, HNF4A and AR. Our data suggest that abnormalities in regulation of metabolic pathways in the immune cells of young NOD mice lead to abnormalities in the immune response pathways and as such may play a role in the initiation of autoimmune diabetes. Thus, targeting metabolism may provide novel approaches to preventing and/or treating autoimmune diabetes. PMID:23071669

  2. Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.

    PubMed

    Wu, Jian; Kakoola, Dorothy N; Lenchik, Nataliya I; Desiderio, Dominic M; Marshall, Dana R; Gerling, Ivan C

    2012-01-01

    Islet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse--a model for human type 1 diabetes (T1D). The molecular events that lead to insulitis and initiate autoimmune diabetes are poorly understood. Since TID is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease. We evaluated the molecular phenotype (mRNA and protein expression) and molecular networks of ex vivo unfractionated spleen leukocytes from 2 and 4 week-old NOD mice in comparison to two control strains. Analysis of the global gene expression profiles and hierarchical clustering revealed that the majority (~90%) of the differentially expressed genes in NOD mice were repressed. Furthermore, analysis using a modern suite of multiple bioinformatics approaches identified abnormal molecular pathways that can be divided broadly into 2 categories: metabolic pathways, which were predominant at 2 weeks, and immune response pathways, which were predominant at 4 weeks. Network analysis by Ingenuity pathway analysis identified key genes/molecules that may play a role in regulating these pathways. These included five that were common to both ages (TNF, HNF4A, IL15, Progesterone, and YWHAZ), and others that were unique to 2 weeks (e.g. MYC/MYCN, TGFB1, and IL2) and to 4 weeks (e.g. IFNG, beta-estradiol, p53, NFKB, AKT, PRKCA, IL12, and HLA-C). Based on the literature, genes that may play a role in regulating metabolic pathways at 2 weeks include Myc and HNF4A, and at 4 weeks, beta-estradiol, p53, Akt, HNF4A and AR. Our data suggest that abnormalities in regulation of metabolic pathways in the immune cells of young NOD mice lead to abnormalities in the immune response pathways and as such may play a role in the initiation of autoimmune diabetes. Thus, targeting metabolism may provide novel approaches to preventing and/or treating autoimmune diabetes. PMID:23071669

  3. Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos

    SciTech Connect

    Levin, M.; Ernst, S.G.

    1997-05-01

    Most work on magnetic field effects focuses on AC fields. The present study demonstrates that exposure to medium-strength (10 mT--0.1 T) static magnetic fields can alter the early embryonic development of two species of sea urchin embryos. Batches of fertilized eggs from two species of urchin were exposed to fields produced by permanent magnets. Samples of the continuous cultures were scored for the timing of the first two cell divisions, time of hatching, and incidence of exogastrulation. It was found that static fields delay the onset of mitosis in both species by an amount dependent on the exposure timing relative to fertilization. The exposure time that caused the maximum effect differed between the two species. Thirty millitesla fields, but not 15 mT fields, caused an eightfold increase in the incidence of exogastrulation in Lytechinus pictus, whereas neither of these fields produced exogastrulation in Strongylocentrotus purpuratus.

  4. The Performance of Silicon Solar Cells Exposed to a Simulated Low Earth Orbit Plasma Environment: Laboratory Ground Tests

    NASA Astrophysics Data System (ADS)

    Abd El-Hameed, Afaf M.; Sabry, M.; Ghitas, Ahmed; El-Tokhy, Fatma S.; Schlosser, Viktor

    2015-12-01

    We have studied the effects of a low earth orbit (LEO) plasma environment on the performance of solar cells. Laboratory ground tests were used to simulate the properties of a low-energy LEO plasma. A Penning plasma source was used to generate plasma from an argon (Ar) gas flow at low pressure (˜10-5 torr) through a vacuum chamber. Diagnostic tools were used to investigate the plasma conditions and their effects on six silicon (Si) solar cells located in the chamber. Alternating current conditions for both biased and unbiased monocrystalline Si solar cells produced from n/ p terrestrial cells with deep junctions were investigated after exposure to plasma fluence for different times up to 14 h. The results obtained confirmed variation of the performance of the cells samples as a consequence of exposure to the plasma.

  5. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy

    SciTech Connect

    Kim, Kangil; Kim, Geunyoung; Yang, Sang Sik; Choi, Jae Duk; Hong, Yong Cheol; Noh, Eun Joo; Lee, Jong-Soo

    2011-02-14

    We propose a plasma-jet device with a micrometer-sized nozzle array for use in a cancer therapy. Also, we show the biological effects of atmospheric-pressure plasma on living cells. Nitrogen-plasma activated a surrogate DNA damage signal transduction pathway, called the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 pathway, suggesting that the nitrogen-plasma generates DNA double-strand breaks. Phosphorylation of H2AX and p53 was detected in the plasma-treated cells, leading to apoptotic cell death. Thus, an effect for the nitrogen plasma in the control of apoptotic cell death provides insight into the how biological effects of the nitrogen-plasma can be applied to the control of cell survival, a finding with potential therapeutic implications.

  6. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy

    NASA Astrophysics Data System (ADS)

    Kim, Kangil; Choi, Jae Duk; Hong, Yong Cheol; Kim, Geunyoung; Noh, Eun Joo; Lee, Jong-Soo; Yang, Sang Sik

    2011-02-01

    We propose a plasma-jet device with a micrometer-sized nozzle array for use in a cancer therapy. Also, we show the biological effects of atmospheric-pressure plasma on living cells. Nitrogen-plasma activated a surrogate DNA damage signal transduction pathway, called the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 pathway, suggesting that the nitrogen-plasma generates DNA double-strand breaks. Phosphorylation of H2AX and p53 was detected in the plasma-treated cells, leading to apoptotic cell death. Thus, an effect for the nitrogen plasma in the control of apoptotic cell death provides insight into the how biological effects of the nitrogen-plasma can be applied to the control of cell survival, a finding with potential therapeutic implications.

  7. Small unilamellar liposomes as a membrane model for cell inactivation by cold atmospheric plasma treatment

    NASA Astrophysics Data System (ADS)

    Maheux, S.; Frache, G.; Thomann, J. S.; Clément, F.; Penny, C.; Belmonte, T.; Duday, D.

    2016-09-01

    Cold atmospheric plasma is thought to be a promising tool for numerous biomedical applications due to its ability to generate a large diversity of reactive species in a controlled way. In some cases, it can also generate pulsed electric fields at the zone of treatment, which can induce processes such as electroporation in cell membranes. However, the interaction of these reactive species and the pulse electric field with cells in a physiological medium is very complex, and we still need a better understanding in order to be useful for future applications. A way to reach this goal is to work with model cell membranes such as liposomes, with the simplest physiological liquid and in a controlled atmosphere in order to limit the number of parallel reactions and processes. In this paper, where this approach has been chosen, 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) small unilamellar vesicles (SUV) have been synthesized in a phosphate buffered aqueous solution, and this solution has been treated by a nanosecond pulsed plasma jet under a pure nitrogen atmosphere. It is only the composition of the plasma gas that has been changed in order to generate different cocktails of reactive species. After the quantification of the main plasma reactive species in the phosphate buffered saline (PBS) solution, structural, surface charge state, and chemical modifications generated on the plasma treated liposomes, due to the interaction with the plasma reactive species, have been carefully characterized. These results allow us to further understand the effect of plasma reactive species on model cell membranes in physiological liquids. The permeation through the liposomal membrane and the reaction of plasma reactive species with molecules encapsulated inside the liposomes have also been evaluated. New processes of degradation are finally presented and discussed, which come from the specific conditions of plasma treatment under the pure nitrogen atmosphere.

  8. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding.

    PubMed

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J

    2015-01-01

    Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

  9. Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for Contraceptive- Associated Abnormal Uterine Bleeding

    PubMed Central

    Guzeloglu Kayisli, Ozlem; Kayisli, Umit A.; Basar, Murat; Semerci, Nihan; Schatz, Frederick; Lockwood, Charles J.

    2015-01-01

    Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA) or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E2+ETO and E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo- and E2-administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription

  10. Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia.

    PubMed

    LeGrand, Jason; Park, Eun Sung; Wang, Hongyang; Gupta, Shalu; Owens, James D; Nelson, Patrick J; DuBois, Wendy; Bair, Thomas; Janz, Siegfried; Mushinski, J Frederic

    2012-01-26

    Tumor progression usually proceeds through several sequential stages, any of which could be targets for interrupting the progression process if one understood these steps at the molecular level. We extracted nascent plasma cell tumor (PCT) cells from within inflammatory oil granulomas (OG) isolated from IP pristane-injected BALB/c.iMyc(Eμ) mice at 5 different time points during tumor progression. We used laser capture microdissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice. Analysis of the expression data used ANOVA and Bayesian estimation of temporal regulation. Genetic pathway analysis was performed using MetaCore (GeneGo) and IPA (Ingenuity). The gene expression profiles of PCT samples and those of undissected OG samples from adjacent sections showed that different genes and pathways were mobilized in the tumor cells during tumor progression, compared with their stroma. Our analysis implicated several genetic pathways in PCT progression, including biphasic (up- and then down-regulation) of the Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein synthesis. The latter led to a biologic validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in vitro. PMID:22147894

  11. Enhanced adherence of mouse fibroblast and vascular cells to plasma modified polyethylene.

    PubMed

    Reznickova, Alena; Novotna, Zdenka; Kolska, Zdenka; Kasalkova, Nikola Slepickova; Rimpelova, Silvie; Svorcik, Vaclav

    2015-01-01

    Since the last decade, tissue engineering has shown a sensational promise in providing more viable alternatives to surgical procedures for harvested tissues, implants and prostheses. Biomedical polymers, such as low-density polyethylene (LDPE), high-density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE), were activated by Ar plasma discharge. Degradation of polymer chains was examined by determination of the thickness of ablated layer. The amount of an ablated polymer layer was measured by gravimetry. Contact angle, measured by goniometry, was studied as a function of plasma exposure and post-exposure aging times. Chemical structure of modified polymers was characterized by angle resolved X-ray photoelectron spectroscopy. Surface chemistry and polarity of the samples were investigated by electrokinetic analysis. Changes in surface morphology were followed using atomic force microscopy. Cytocompatibility of plasma activated polyethylene foils was studied using two distinct model cell lines; VSMCs (vascular smooth muscle cells) as a model for vascular graft testing and connective tissue cells L929 (mouse fibroblasts) approved for standardized material cytotoxicity testing. Specifically, the cell number, morphology, and metabolic activity of the adhered and proliferated cells on the polyethylene matrices were studied in vitro. It was found that the plasma treatment caused ablation of the polymers, resulting in dramatic changes in their surface morphology and roughness. ARXPS and electrokinetic measurements revealed oxidation of the polymer surface. It was found that plasma activation has a positive effect on the adhesion and proliferation of VSMCs and L929 cells. PMID:25953566

  12. DEVELOPMENT OF SOLID-STATE DRIVERS FOR THE NIF PLASMA ELECTRODE POCKELS CELL

    SciTech Connect

    Barbosa, F; Arnold, P A; McHale, G B; James, G; Brown, G; Cook, E G; Hickman, B C

    2008-05-14

    Large aperture Plasma Electrode Pockels Cells (PEPC) are an enabling technology in the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory. The Pockels cell allows the NIF laser to take advantage of multipass amplifier architecture, thus reducing costs and physical size of the facility. Each Pockels cell comprises four 40-cm x 40-cm apertures arranged in a 4 x 1 array. The combination of the Pockels cell and a thin-film polarizer, configured in a 4 x 1 array, form an optical switch that is key to achieving multi-pass operation. Solid-state Plasma Pulse Generators (PPGs) and high current high voltage solid-state Switch Pulse Generators (SPGs) have been developed for use in the PEPC. The solid-state plasma pulse generators initiate and maintain plasma within the cells; each pulser is capable of delivering 60J of energy to each plasma channel. Deployment of the solid-state PPGs has been completed in NIF. The MOSFET-switched SPG is capable of delivering a requisite fast rise time, 17kV flattop pulse to the cells nonlinear crystals. A complete software and hardware control system has been developed and is currently being tested for use on the solid-state SPGs. Also a transmission line modeling, development, and testing effort is in process, in support of NIFs Advanced Radiographic Capabilities (ARC). Work is scheduled for completion by the end of the calendar year.

  13. Overexpression of TSC-22 (transforming growth factor- β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice.

    PubMed

    Uchida, Daisuke; Kawamata, Hitoshi; Omotehara, Fumie; Miwa, Yoshihiro; Horiuchi, Hideki; Furihata, Tadashi; Tachibana, Masatsugu; Fujimori, Takahiro

    2016-03-22

    In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-β stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease-died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells. PMID:26872059

  14. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors.

    PubMed Central

    Daughaday, W H; Kapadia, M

    1989-01-01

    We reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated "big IGF-II." We now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Saphadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result. PMID:2771956

  15. Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development

    PubMed Central

    Kumar, Manish; Camlin, Nicole J.; Holt, Janet E.; Teixeira, Jose M.; McLaughlin, Eileen A.; Tanwar, Pradeep S.

    2016-01-01

    All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/βcatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of βcatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1ex3cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1ex3cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth. PMID:27265527

  16. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

    SciTech Connect

    Daughaday, W.H.; Kapadia, M. )

    1989-09-01

    The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.

  17. Overexpression of TSC-22 (transforming growth factor-β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice

    PubMed Central

    Miwa, Yoshihiro; Horiuchi, Hideki; Furihata, Tadashi; Tachibana, Masatsugu; Fujimori, Takahiro

    2016-01-01

    In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-β stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease-died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells. PMID:26872059

  18. Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development.

    PubMed

    Kumar, Manish; Camlin, Nicole J; Holt, Janet E; Teixeira, Jose M; McLaughlin, Eileen A; Tanwar, Pradeep S

    2016-01-01

    All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/βcatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of βcatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1(ex3)cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1(ex3)cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth. PMID:27265527

  19. Abnormal UP/DOWN Membrane Potential Dynamics Coupled with the Neocortical Slow Oscillation in Dentate Granule Cells during the Latent Phase of Temporal Lobe Epilepsy123

    PubMed Central

    Ouedraogo, David W.; Lenck-Santini, Pierre-Pascal; Marti, Geoffrey; Robbe, David; Crépel, Valérie

    2016-01-01

    The dentate gyrus, a major entry point to the hippocampus, gates (or filters) incoming information from the cortex. During sleep or anesthesia, the slow-wave oscillation (SWO) orchestrates hippocampus–neocortex communication, which is important for memory formation. The dentate gate is altered in temporal lobe epilepsy (TLE) early during epileptogenesis, which favors the propagation of pathological activities. Yet, whether the gating of physiological SWO by dentate granule cells (DGCs) is altered in TLE has remained unexplored. We combined intracellular recordings of membrane potential (Vm) of DGCs and local field potential recordings of the SWO in parietal cortex in anesthetized rats early during epileptogenesis [post-status epilepticus (SE) rats]. As expected, in control rats, the Vm of DGCs weakly and rarely oscillated in the SWO frequency range. In contrast, in post-SE rats, the Vm of DGCs displayed strong and long-lasting SWO. In these cells, clear UP and DOWN states, in phase with the neocortical SWO, led to a bimodal Vm distribution. In post-SE rats, the firing of DGCs was increased and more temporally modulated by the neocortical SWO. We conclude that UP/DOWN state dynamics dominate the Vm of DGCs and firing early during epileptogenesis. This abnormally strong neocortical influence on the dynamics of DGCs may profoundly modify the hippocampus–neocortex dialogue during sleep and associated cognitive functions. PMID:27257629

  20. Reduced fitness and abnormal cardiopulmonary responses to maximal exercise testing in children and young adults with sickle cell anemia

    PubMed Central

    Liem, Robert I; Reddy, Madhuri; Pelligra, Stephanie A; Savant, Adrienne P; Fernhall, Bo; Rodeghier, Mark; Thompson, Alexis A

    2015-01-01

    Physiologic contributors to reduced exercise capacity in individuals with sickle cell anemia (SCA) are not well understood. The objective of this study was to characterize the cardiopulmonary response to maximal cardiopulmonary exercise testing (CPET) and determine factors associated with reduced exercise capacity among children and young adults with SCA. A cross-sectional cohort of 60 children and young adults (mean 15.1 ± 3.4 years) with hemoglobin SS or S/β0 thalassemia and 30 matched controls (mean 14.6 ± 3.5 years) without SCA or sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle ergometry protocol with breath-by-breath, gas exchange analysis. Compared to controls without SCA, subjects with SCA demonstrated significantly lower peak VO2 (26.9 ± 6.9 vs. 37.0 ± 9.2 mL/kg/min, P < 0.001). Subjects demonstrated slower oxygen uptake (ΔVO2/ΔWR, 9 ± 2 vs. 12 ± 2 mL/min/watt, P < 0.001) and lower oxygen pulse (ΔVO2/ΔHR, 12 ± 4 vs. 20 ± 7 mL/beat, P < 0.001) as well as reduced oxygen uptake efficiency (ΔVE/ΔVO2, 42 ± 8 vs. 32 ± 5, P < 0.001) and ventilation efficiency (ΔVE/ΔVCO2, 30.3 ± 3.7 vs. 27.3 ± 2.5, P < 0.001) during CPET. Peak VO2 remained significantly lower in subjects with SCA after adjusting for age, se