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Sample records for jeg-3 human choriocarcinoma

  1. MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8

    SciTech Connect

    Shi, Dazun; Tan, Zhihui; Lu, Rong; Yang, Wenqing; Zhang, Yi

    2014-08-08

    Highlights: • The miR-218 expression was decreased in choriocarcinoma cell lines. • The Fbxw8 protein expression was increased in choriocarcinoma cell lines. • We show that Fbxw8 is bona-fide target of miR-218 in JEG-3. • Ectopic miR-218 expression inhibits the proliferation of JEG-3 via Fbxw8. • Overexpression of miR-218 affected cyclin A and p27 expression via Fbxw8. - Abstract: MicroRNAs (miRNAs) are endogenous 19–25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased in human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct target of miR-218. Overexpression of miR-218 inhibited cell growth arrest at G2/M phase, suppressed the protein levels of cyclin A and up-regulated the expression levels of p27 through decreasing the levels of Fbxw8. On the other hand, forced expression of Fbxw8 partly rescued the effect of miR-218 in the cells, attenuated cell proliferation decrease the percentage of cells at G2/M phase, induced cyclin A protein expression and suppressed the protein level of p27 through up-regulating the levels of Fbxw8. Taken together, these findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future.

  2. Aromatase in the human choriocarcinoma JEG-3: inhibition by R 76 713 in cultured cells and in tumors grown in nude mice.

    PubMed

    Krekels, M D; Wouters, W; De Coster, R; Van Ginckel, R; Leonaers, A; Janssen, P A

    1991-04-01

    The aromatase enzyme and its inhibition by R 76 713 were characterized in the JEG-3 choriocarcinoma cell line in culture and in JEG-3 tumors grown in nude mice. Optimal cell culture parameters and enzyme reaction conditions for the determination of aromatase activity were established. Under these conditions, in vitro JEG-3 aromatase was inhibited by R 76 713 with IC50-values of 7.6 +/- 0.5 nM and 2.7 +/- 1.1 nM using 500 nM of androstenedione and testosterone as substrate respectively. The Km-value of the aromatase enzyme with androstenedione as substrate was 62 +/- 19 nM; with testosterone as substrate, a value of 166 +/- 27 nM was found. In the presence of increasing concentrations of R 76 713, the Km-values increased while the Vmax remained unchanged. Using androstenedione and testosterone as substrate Lineweaver-Burk analysis of the data showed Ki-values for R 76 713 of 0.43 +/- 0.06 nM and 0.47 +/- 0.39 nM respectively. R 76 713 appeared to competitively inhibit the JEG-3 aromatase. Aromatase could easily be measured in homogenates of JEG-3 tumors grown in nude mice and showed Km-values similar to those found for JEG-3 cells in vitro. IC50-values for inhibition of tumor aromatase by R 76 713 were also similar to those found in cultured cells. Tumor aromatase measured ex vivo, 2 h after a single oral administration of R 76 713 was dose-dependently inhibited. An ED50-value of 0.05 mg/kg was calculated. The JEG-3 choriocarcinoma proved to be a useful aromatase model enabling the comparative study of aromatase inhibition in vitro and in vivo. PMID:2031856

  3. Over-expression of stomatin causes syncytium formation in nonfusogenic JEG-3 choriocarcinoma placental cells.

    PubMed

    Chen, Tung-Wei; Liu, Hong-Wen; Liou, Yi-Jia; Lee, Jui-Hao; Lin, Chi-Hung

    2016-08-01

    Placental trophoblast differentiation involves the continuous fusion of mononuclear cytotrophoblasts. However, except for syncytin, little is known about the detailed mechanisms underlying trophoblast fusion. A previous study indicated that lipid rafts play an important role in HTLV-1 syncytium formation. To identify proteins that may be involved in placental trophoblast differentiation, we examined stomatin, an important lipid-raft protein that localizes to detergent-resistant membrane domains. The syncytium and human chorionic gonadotropin (β-hCG; a marker of placental trophoblast differentiation) were visualized by immunofluorescence staining. We found that overexpression of stomatin in the nonfusogenic JEG-3 cell line caused syncytium formation and increased the fusion index of cells. Treating these cells with N(6) ,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate further increased cell fusion by stomatin. β-hCG was found in a few JEG-3 cells overexpressing stomatin at 48 h, and its levels increased dramatically at 72 h along with the formation of the multinuclear syncytium. RNA interference was used to decrease stomatin expression in BeWo cells, a fusogenic human choriocarcinoma cell line. After knockdown for 72 h, stomatin levels decreased by almost 95%. The fusion indexes of control and stomatin-knockdown cells at 72 h were 9.4 and 6.5%, respectively. Our data indicated that stomatin could trigger syncytium formation and upregulate β-hCG for cell fusion in nonfusogenic JEG-3 cells. Downregulation of stomatin slightly inhibited the fusion index of fusogenic BeWo cells. Thus, these data suggested that stomatin plays an important role in trophoblast differentiation. PMID:27306251

  4. [Detection of gamma-interferon mRNA in JEG-3 choriocarcinoma cell line by means of polymerase chain reaction].

    PubMed

    Fülöp, V; Szigetvári, I; Szepesi, J; Gáti, I

    1994-05-01

    To investigate the pathogenesis of choriocarcinoma the authors employed a newly developed gene amplification method by reverse polymerase chain reaction for the detection of gamma-interferon messenger RNA in JEG-3 choriocarcinoma cell line. Polymerase chain reaction products were analysed by agarose gel electrophoresis. Using 1 Kb DNA ladder as a marker, 84 base-pair fragment was selectively amplified correlating with published gamma-interferon gene fragment length. Because cDNA contains a virtually complete copy of the mRNA this method provides an evidence for the expression of gamma-interferon gene in JEG-3 choriocarcinoma cell line. Based on these results a potential autocrine mechanism may be present in JEG-3 choriocarcinoma cell line. PMID:8183543

  5. Antiproliferative and proapoptotic effects of bisphenol A on human trophoblastic JEG-3 cells.

    PubMed

    Morice, Lucie; Benaîtreau, Delphine; Dieudonné, Marie-Noëlle; Morvan, Corinne; Serazin, Valérie; de Mazancourt, Philippe; Pecquery, René; Dos Santos, Esther

    2011-07-01

    Different studies performed in rodents revealed that bisphenol-A (BPA), an environmental compound, altered early embryonic development. However, little is known concerning the direct effects of BPA on human implantation process. Thus, we decided to study in vitro BPA's effects on proliferative capacities of the human trophoblastic cell line, JEG-3. For this purpose, we first have shown that JEG-3 cells express the specific BPA receptor, namely estrogen-related receptor γ1 (ERRγ1). Secondly, we demonstrated that BPA did not exert any cytotoxic action in JEG-3 cells up to 10(-6)M. Moreover [(3)H]-thymidine incorporation experiments revealed that BPA significantly reduced cell proliferation. The results also showed that BPA induced JEG-3 apoptosis capacity as reflected by DNA fragmentation experiments. In conclusion, we describe here the direct impact of BPA on trophoblastic cell number mediated through both anti-proliferative and pro-apoptotic effects. PMID:21621606

  6. Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression.

    PubMed

    Cui, Hong; Chen, Jing; Na, Quan

    2016-01-01

    Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role in the chronic carrier state in China. In our studies, the response of trophoblast cell and choriocarcinoma cell to HBV infection regarding the expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed in HTR-8/SVneo cells and JEG-3-CD133-2(+) cells after HBV infection than those in HTR-8-CD133-2(-) cells and JEG-3 cells. Our main finding is that CD133-negative cells (HTR-8-CD133-2(-) and JEG-3) are prone to HBV infection. In the last, our data indicated that the activation of Smad signaling pathway and the induction of epithelial-mesenchymal transition (EMT) in CD133-negative cells after HBV infection. In summary, our study demonstrated that CD133 is a key factor that mediated HBV infection to trophoblast cell and choriocarcinoma cell. PMID:27508045

  7. Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression

    PubMed Central

    Cui, Hong; Chen, Jing; Na, Quan

    2016-01-01

    Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role in the chronic carrier state in China. In our studies, the response of trophoblast cell and choriocarcinoma cell to HBV infection regarding the expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed in HTR-8/SVneo cells and JEG-3-CD133-2+ cells after HBV infection than those in HTR-8-CD133-2- cells and JEG-3 cells. Our main finding is that CD133-negative cells (HTR-8-CD133-2- and JEG-3) are prone to HBV infection. In the last, our data indicated that the activation of Smad signaling pathway and the induction of epithelial-mesenchymal transition (EMT) in CD133-negative cells after HBV infection. In summary, our study demonstrated that CD133 is a key factor that mediated HBV infection to trophoblast cell and choriocarcinoma cell. PMID:27508045

  8. Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling

    SciTech Connect

    Peng Sha; Miao Chenglin; Li Jing; Fan Xiujun; Cao Yujing; Duan Enkui . E-mail: duane@ioz.ac.cn

    2006-11-24

    Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas.

  9. Choriocarcinoma

    MedlinePlus

    ... with a choriocarcinoma had a hydatidiform mole, or molar pregnancy. Choriocarcinomas may also occur after an early pregnancy ... bleeding in a woman who recently had a hydatidiform mole or pregnancy. Other symptoms may include: Irregular vaginal ...

  10. Expression and Functional Activity of the Human Bitter Taste Receptor TAS2R38 in Human Placental Tissues and JEG-3 Cells.

    PubMed

    Wölfle, Ute; Elsholz, Floriana A; Kersten, Astrid; Haarhaus, Birgit; Schumacher, Udo; Schempp, Christoph M

    2016-01-01

    Bitter taste receptors (TAS2Rs) are expressed in mucous epithelial cells of the tongue but also outside the gustatory system in epithelial cells of the colon, stomach and bladder, in the upper respiratory tract, in the cornified squamous epithelium of the skin as well as in airway smooth muscle cells, in the testis and in the brain. In the present work we addressed the question if bitter taste receptors might also be expressed in other epithelial tissues as well. By staining a tissue microarray with 45 tissue spots from healthy human donors with an antibody directed against the best characterized bitter taste receptor TAS2R38, we observed an unexpected strong TAS2R38 expression in the amniotic epithelium, syncytiotrophoblast and decidua cells of the human placenta. To analyze the functionality we first determined the TAS2R38 expression in the placental cell line JEG-3. Stimulation of these cells with diphenidol, a clinically used antiemetic agent that binds TAS2Rs including TAS2R38, demonstrated the functionality of the TAS2Rs by inducing calcium influx. Restriction enzyme based detection of the TAS2R38 gene allele identified JEG-3 cells as PTC (phenylthiocarbamide)-taster cell line. Calcium influx induced by PTC in JEG-3 cells could be inhibited with the recently described TAS2R38 inhibitor probenecid and proved the specificity of the TAS2R38 activation. The expression of TAS2R38 in human placental tissues points to further new functions and hitherto unknown endogenous ligands of TAS2Rs far beyond bitter tasting. PMID:26950109

  11. Negative Effects of SRD5A1 on Nuclear Activity of Progesterone Receptor Isoform B in JEG3 Cells.

    PubMed

    Miao, Zhuo; Sun, Min; Jiang, Feng; Yao, Yuanqing; Li, Yi

    2016-02-01

    Progesterone withdrawal signals labor in mammals. Elevated intracellular metabolism contributes to progesterone functional withdrawal through unknown mechanism, which is thought to act via progesterone receptor (PR). This study aims to investigate molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. We investigated the role of 5α-reductase type I (SRD5A1) in enzymatic catalysis of progesterone and loss of PR function in a human trophoblast choriocarcinoma cell line JEG3. The PR isoform B (PR-B) was robustly expressed in JEG3 cells. The SRD5A1 small-interfering RNA knockdown led to significant increase in PR-B nuclear import, ectopic, whereas SRD5A1 overexpression resulted in remarkable inhibition of nuclear PR-B in P4-treated cells. Repression of SRD5A1 activated PR-B responsive gene, whereas overexpression of SRD5A1 possessed an inhibitory effect. JEG3 cell line is a valuable tool to study mechanisms responsible for loss of PR function and screening of drugs for preterm birth treatment. Our study aims to investigate the molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. PMID:26243543

  12. HSPC117 Is Regulated by Epigenetic Modification and Is Involved in the Migration of JEG-3 Cells

    PubMed Central

    Ma, Hong; Qi, Mei-Yu; Zhang, Xu; Zhang, Yue-Ling; Wang, Liang; Li, Zhong-Qiu; Fu, Bo; Wang, Wen-Tao; Liu, Di

    2014-01-01

    The human hematopoietic stem/progenitor cell 117 (HSPC117) protein is an essential component of protein complexes and has been identified to be involved in many important functions. However, how this gene expression is regulated and whether the HSPC117 gene affects cell migration is still unknown. The aim of this study was to identify whether HSPC117 mRNA expression is regulated by epigenetic modification and whether HSPC117 expression level affects the expression of matrix metalloproteinase 2 (MMP 2), matrix metalloproteinase 14 (MMP 14), and tissue inhibitor of metalloproteinases 2 (TIMP 2), and further affects human placenta choriocarcinoma cell (JEG-3) migration speed. In our epigenetic modification experiment, JEG-3 cells were cultured in medium with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC), the histone deacetylase (HDAC) inhibitor trichostatin A (TSA), or both inhibitors. Then, the HSPC117 mRNA and protein expressions were assessed using real-time quantitative PCR (qPCR) and Western blot assay. The results showed that, compared to the control, HSPC117 mRNA expression was increased by TSA or 5-aza-dC. The highest HSPC117 expression level was found after treatment with both 5-aza-dC and TSA. Further, in order to investigate the effect of HSPC117 on MMP 2, MMP 14, and TIMP 2 mRNA expressions, pEGFP-C1-HSPC117 plasmids were transfected into JEG-3 cells to improve the expression of HSPC117 in the JEG-3 cells. Then, the mRNA expression levels of MMP 2, MMP 14, TIMP 2, and the speed of cell migration were assessed using the scratch wound assay. The results showed that over-expression of HSPC117 mRNA reduced MMP 2 and MMP 14 mRNA expression, while TIMP 2 mRNA expression was up-regulated. The scratch wound assay showed that the migration speed of JEG-3 cells was slower than the non-transfected group and the C1-transfected group. All of these results indicate that HSPC117 mRNA expression is regulated by epigenetic modification; over

  13. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells

    SciTech Connect

    Ritvos, O.; Ranta, T.; Jalkanen, J.; Suikkari, A.M.; Voutilainen, R.; Bohn, H.; Rutanen, E.M.

    1988-05-01

    The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound (125I)iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of (125I) iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of (125I) iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with (125I)iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-(3H)aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells.

  14. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    SciTech Connect

    Wang, Ji-meng; Zhao, Hong-xi; Wang, Li; Gao, Zhi-ying; Yao, Yuan-qing

    2013-05-10

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

  15. Placenta-Enriched LincRNAs MIR503HG and LINC00629 Decrease Migration and Invasion Potential of JEG-3 Cell Line

    PubMed Central

    Muys, Bruna Rodrigues; Lorenzi, Júlio Cesar Cetrulo; Zanette, Dalila Luciola; Bueno, Rafaela de Barros Lima e; de Araújo, Luíza Ferreira; Dinarte-Santos, Anemari Ramos; Alves, Cleidson Pádua; Ramão, Anelisa; de Molfetta, Greice Andreotti; Vidal, Daniel Onofre; Silva, Wilson Araújo

    2016-01-01

    LINC00629 and MIR503HG are long intergenic non-coding RNAs (lincRNAs) mapped on chromosome X (Xq26), a region enriched for genes associated with human reproduction. Genes highly expressed in normal reproductive tissues and cancers (CT genes) are well known as potential tumor biomarkers. This study aimed to characterize the structure, expression, function and regulation mechanism of MIR503HG and LINC00629 lincRNAs. According to our data, MIR503HG expression was almost exclusive to placenta and LINC00629 was highly expressed in placenta and other reproductive tissues. Further analysis, using a cancer cell lines panel, showed that MIR503HG and LINC00629 were expressed in 50% and 100% of the cancer cell lines, respectively. MIR503HG was expressed predominantly in the nucleus of JEG-3 choriocarcinoma cells. We observed a positively correlated expression between MIR503HG and LINC00629, and between the lincRNAs and neighboring miRNAs. Also, both LINC00629 and MIR503GH could be negatively regulated by DNA methylation in an indirect way. Additionally, we identified new transcripts for MIR503HG and LINC00629 that are relatively conserved when compared to other primates. Furthermore, we found that overexpression of MIR503HG2 and the three-exon LINC00629 new isoforms decreased invasion and migration potential of JEG-3 tumor cell line. In conclusion, our results suggest that lincRNAs MIR503HG and LINC00629 impaired migration and invasion capacities in a choriocarcinoma in vitro model, indicating a potential role in human reproduction and tumorigenesis. Moreover, the MIR503HG expression pattern found here could indicate a putative new tumor biomarker. PMID:27023770

  16. B-esterase determination and organophosphate insecticide inhibitory effects in JEG-3 trophoblasts.

    PubMed

    Espinoza, Marlon; Rivero Osimani, Valeria; Sánchez, Victoria; Rosenbaum, Enrique; Guiñazú, Natalia

    2016-04-01

    The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 0.33 and 0.26mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4h treatment while Cp showed the highest inhibition profile at 24h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy. PMID:26790371

  17. Green tea (-)-epigallocatechin gallate induced growth inhibition of human placental choriocarcinoma cells.

    PubMed

    Shih, Li-Jane; Lin, Yu-Ren; Lin, Cheng-Kuo; Liu, Hang-Shen; Kao, Yung-Hsi

    2016-05-01

    This study investigated the pathways involved in the effect of green tea epigallocatechin gallate (EGCG) on mitogenesis in BeWo, JEG-3, and JAR placental choriocarcinoma cells. EGCG inhibited cell proliferation in dose-dependent and time-dependent manners, as indicated by the number of cells and incorporation of bromodeoxyuridine (BrdU). A catechin-specific effect of green tea was evident; EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in suppressing cell growth. When all three of the mitogen-activated protein kinase (MAPK) subfamilies, i.e., ERK, p38, and JNK, were examined, EGCG significantly increased levels of phospho-ERK1/2 (pERK1/2) and phospho-p38 (pp38) and did not alter the total protein levels of ERK1/2, p38 MAPK, JNK, and phospho-JNK. EGCG-induced increases in the levels of pERK1/2 and pp38 proteins were prevented by pre-treatment with specific inhibitors of ERK1/2 MAPK and p38 MAPK, respectively. These inhibitors also suppressed EGCG-induced decreases in both cell number and BrdU incorporation. Moreover, pre-treatment with an AMP-activated protein kinase (AMPK) inhibitor prevented the actions of EGCG on proliferation and AMPK phosphorylation. These data suggest that EGCG mediates choriocarcinoma cell growth via the AMPK, ERK, and p38 pathways, but not JNK pathway. PMID:27208402

  18. Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Mingjun; Yang, Jinmei; Shu, Jing; Fu, Changhong; Liu, Shengnan; Xu, Ge; Zhang, Dechun

    2014-11-01

    We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway.

  19. Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells

    PubMed Central

    2014-01-01

    We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway. PMID:25411570

  20. Cytotoxicity induced by nanobacteria and nanohydroxyapatites in human choriocarcinoma cells.

    PubMed

    Zhang, Mingjun; Yang, Jinmei; Shu, Jing; Fu, Changhong; Liu, Shengnan; Xu, Ge; Zhang, Dechun

    2014-01-01

    We explored the cytotoxic effects of nanobacteria (NB) and nanohydroxyapatites (nHAPs) against human choriocarcinoma cells (JAR) and the mechanisms of action underlying their cytotoxicity. JAR cells were co-cultured with NB and nHAPs for 48 h, and ultrastructural changes were more readily induced by NB than nHAPs. Autophagy in the plasma of JAR cells were observed in the NB group. The rate of apoptosis induced by NB was higher than that for nHAPs. The expression of Bax and FasR proteins in the NB group was stronger than that for the nHAP group. NB probably resulted in autophagic formation. Apoptosis was possibly activated via FasL binding to the FasR signaling pathway. PMID:25411570

  1. Human Hemochromatosis Protein (HFE) Immunoperoxidase Stain Highlights Choriocarcinoma within Mixed Germ Cell Tumors.

    PubMed

    Cox, Jesse L; Talmon, Geoffrey A; Koepsell, Scott A

    2016-01-01

    Identification of choriocarcinoma within a germ cell tumor can have major implications for the subsequent staging and treatment of testicular neoplasms. Immunoperoxidase staining greatly enhances the speed and sensitivity of identifying occult, though clinically significant, tumor components. In mixed germ cell tumors, staining for beta-human chorionic gonadotropin (β-hCG) has been historically used to assess for the presence and burden of choriocarcinoma. However, current β-hCG stains produce variable, intense staining of trophoblastic elements and surrounding tissues, clouding the assessment of true-positive staining. Human hemochromatosis protein (HFE) is a membrane bound mediator of iron transport expressed at high levels within placenta. Additionally, previous reports have demonstrated that choriocarcinoma cell lines express HFE, although in vivo expression had not been examined. To address whether HFE can stain trophoblastic elements, HFE immunohistochemistry was conducted in choriocarcinoma (n = 4), mixed germ cell tumors (n = 11), seminoma (n = 4), and placenta (n = 11). HFE consistently demonstrated cytoplasmic and membranous staining, highlighting both syncytiotrophoblasts and cytotrophoblasts within choriocarcinoma and placenta. Staining of intratumoral white blood cells was observed within seminomas and mixed germ cell tumors, corroborating prior reports stating that HFE highlights monocytes and macrophages. Taken together, HFE may serve as an alternative target from β-hCG for immunoperoxidase studies when highlighting choriocarcinoma. PMID:27034532

  2. Human Hemochromatosis Protein (HFE) Immunoperoxidase Stain Highlights Choriocarcinoma within Mixed Germ Cell Tumors

    PubMed Central

    Talmon, Geoffrey A.; Koepsell, Scott A.

    2016-01-01

    Identification of choriocarcinoma within a germ cell tumor can have major implications for the subsequent staging and treatment of testicular neoplasms. Immunoperoxidase staining greatly enhances the speed and sensitivity of identifying occult, though clinically significant, tumor components. In mixed germ cell tumors, staining for beta-human chorionic gonadotropin (β-hCG) has been historically used to assess for the presence and burden of choriocarcinoma. However, current β-hCG stains produce variable, intense staining of trophoblastic elements and surrounding tissues, clouding the assessment of true-positive staining. Human hemochromatosis protein (HFE) is a membrane bound mediator of iron transport expressed at high levels within placenta. Additionally, previous reports have demonstrated that choriocarcinoma cell lines express HFE, although in vivo expression had not been examined. To address whether HFE can stain trophoblastic elements, HFE immunohistochemistry was conducted in choriocarcinoma (n = 4), mixed germ cell tumors (n = 11), seminoma (n = 4), and placenta (n = 11). HFE consistently demonstrated cytoplasmic and membranous staining, highlighting both syncytiotrophoblasts and cytotrophoblasts within choriocarcinoma and placenta. Staining of intratumoral white blood cells was observed within seminomas and mixed germ cell tumors, corroborating prior reports stating that HFE highlights monocytes and macrophages. Taken together, HFE may serve as an alternative target from β-hCG for immunoperoxidase studies when highlighting choriocarcinoma. PMID:27034532

  3. Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines

    SciTech Connect

    Ren, S.G.; Braunstein, G.D. )

    1991-03-01

    Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively. Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and (35S)methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable (35S)methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable (35S)methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells.

  4. Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity during the first trimester of pregnancy.

    PubMed

    Mock, P; Kovalevskaya, G; O'Connor, J F; Campana, A

    2000-10-01

    The objective of this study was to evaluate the distribution of choriocarcinoma-like human chorionic gonadotrophin (HCG) isoforms during first trimester pregnancy and their relationship with in-vitro HCG bioactivity. This was done by means of a retrospective analysis of patients' sera with first trimester normal intrauterine and abnormal (ectopic) pregnancies. Serum samples were obtained from 38 women with an amenorrhoea of <10 weeks. From these, 19 had a normal intrauterine pregnancy (IUP) and 19 an ectopic pregnancy (EP). Total immunoreactive HCG (HCGi), free beta-HCGi and oestradiol were measured by enzyme immunoassays and bioactive HCG by the mouse Leydig cell bioassay. The alterations in HCG isoform content were measured by the combination of two immunometric assays, B152 for choriocarcinoma-like HCG and B109 for intact HCG detection and expressed as the B152/B109 ratio. Choriocarcinoma-like HCG isoforms ratio measured by B152 and B109 assays was significantly higher in the low subgroups of free beta-HCGi and gestational age (P = 0.0111 and 0.0036 respectively). Whereas bioactive to immunoreactive HCG ratios (b/i ratio) were significantly higher when free beta-HCGi concentrations were low (P = 0.0010), no correlation was found between the variation of bioactivity (b/i ratio) and the proportion of choriocarcinoma-like HCG isoforms (B159/B108). It is concluded that in first trimester pregnancies (i) the modulation of HCG in-vitro bioactivity is not related to the variation of choriocarcinoma-like HCG isoforms secretion and (ii) the amount of choriocarcinoma-like HCG isoforms secreted by the early trophoblast is predominant and may be the result of an early developmental regulation of glycosylation enzyme. PMID:11006201

  5. Downregulation of the Gli Transcription Factors Regulator Kif7 Facilitates Cell Survival and Migration of Choriocarcinoma Cells

    PubMed Central

    Ho, Joanna; Du, Yanan; Wong, Oscar Gee-Wan; Siu, Michelle K. Y.; Chan, Karen K. L.; Cheung, Annie N. Y.

    2014-01-01

    The kinesin protein Kif7 has been recognized as an integral component of hedgehog signalling. Aberrant activation of hedgehog signalling has been implicated in many human solid tumours. Gestational trophoblastic disease includes frankly malignant choriocarcinoma and potentially malignant hydatidiform mole. Here we investigated the hedgehog signalling components expression profiles in gestational trophoblastic disease. Downregulation of Gli1, Gli2, Gli3 and Kif7 was demonstrated in clinical samples of choriocarcinoma and hydatidiform moles as well as choriocarcinoma cell lines when compared with normal placentas. Ectopic expression of Kif7 in two choriocarcinoma cell lines JAR and JEG-3 led to a decrease in cell growth and increase in apoptosis demonstrated by MTT and TUNEL assays, respectively. Overexpression of Kif7 also led to suppressed cell migration through transwell assay. In contrast, knocking down Kif7 in HTR-8/SVneo, an immortalized trophoblast cell line, increased cell number over time and increased the migratory ability of the cells. Taken together, Kif7 may contribute to pathogenesis of gestational trophoblastic disease through enhancing survival and promoting dissemination of trophoblasts. PMID:25265279

  6. Uterine choriocarcinoma accompanied by an extremely high human chorionic gonadotropin level and thyrotoxicosis.

    PubMed

    Hsieh, Tsung-Ying; Hsu, Keng-Fu; Kuo, Pao-Lin; Huang, Soon-Cen

    2008-04-01

    The conventional treatments given to a 24-year-old woman with metastatic uterine choriocarcinoma and clinical and biochemical thyrotoxicosis did not appear to have any effect, probably due to an extremely high serum human chorionic gonadotropin (hCG) level which was up to 11,910,000 mIU/mL, and were initially underscored in light of the 'high-dose hook effect'. To our knowledge, no extremely high hCG level in a uterine choriocarcinoma patient has been reported in the literature. Her decapacitating symptoms subsided after the first course of chemotherapy by etoposide, methotrexate, and actinomycin D-cyclophosphamide and vincristine (EMA-CO) regimen. The serum hCG level, which reflects the quantification of host tumor burden, returned to the reference range after the fifth course of chemotherapy and the thyroid function reached euthyroid status before the third course of chemotherapy; two final courses were administered after the hCG level became undetectable. Two years after remission of disease, the patient experienced a normal pregnancy, and a term baby girl was delivered vaginally. No recurrence of uterine choriocarcinoma has been noted for 7 years. PMID:18412797

  7. Identification of a functional transcriptional factor AP-1 site in the sheep interferon tau gene that mediates a response to PMA in JEG3 cells.

    PubMed Central

    Yamaguchi, H; Ikeda, Y; Moreno, J I; Katsumura, M; Miyazawa, T; Takahashi, E; Imakawa, K; Sakai, S; Christenson, R K

    1999-01-01

    To examine regulatory mechanisms of sheep interferon tau (oIFNtau) gene expression, potential enhancer/silencer elements of the oIFNtau gene were examined using a transient transfection system with oIFNtau gene-chloramphenicol acetyltransferase (oIFNtau-CAT) reporter constructs in human choriocarcinoma cells, JEG3. Experiments with 5'-deletion constructs revealed that the upstream regions from bases -654 to -607 and from bases -606 to -555 were essential for oIFNtau gene expression. In a heterologous transcriptional system in which the upstream regions of oIFNtau were inserted in front of simian virus 40 (SV40) promoter, the regions between bases -654 and -555 were determined as being the enhancer region required for oIFNtau-SV40-CAT transactivation. A subsequent study with the oIFNtau-CAT constructs lacking the upstream region between bases -542 and -124 revealed that, in addition to the further upstream region between bases -1000 and -654, the sequences from bases -543 to -452 seemed to act as silencer regions. The oIFNtau-CAT constructs with site-specific mutagenesis revealed that multiple enhancer elements existed between bases -654 and -555 of the oIFNtau gene. On the basis of nucleotide sequence analysis, there are numerous sites between bases -654 and -555 to which potential transcriptional factors, AP-1, GATA and GATA-related proteins, could bind. Furthermore, gel mobility-shift assays revealed that AP-1 or other nuclear factors could bind to these elements. In co-transfection studies, the expression of c-Jun plus c-Fos enhanced the transactivation of oIFNtau-CAT but the expression of GATA-1, GATA-2 or GATA-3 did not. Taken together, these results suggest that the upstream region between bases -654 and -555 could be considered as the enhancer region for oIFNtau gene transactivation. PMID:10359663

  8. Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells.

    PubMed

    Wong, N C; Novakovic, B; Weinrich, B; Dewi, C; Andronikos, R; Sibson, M; Macrae, F; Morley, R; Pertile, M D; Craig, J M; Saffery, R

    2008-09-01

    Methylation of the human APC gene promoter is associated with several different types of cancers and has also been documented in some pre-cancerous tissues. We have examined the methylation of APC gene promoters in human placenta and choriocarcinoma cells. This revealed a general hypomethylation of the APC-1b promoter and a pattern with monoallelic methylation of the APC-1a promoter in full term placental tissue. However, there was no evidence of a parent-of-origin effect, suggesting random post zygotic origin of methylation. Increased methylation of this promoter was observed in all choriocarcinoma-derived trophoblast cell lines, suggesting a trophoblastic origin of placental APC methylation and implicating APC hypermethylation in the development of this group of gestational tumours. Our demonstration of placental methylation of the APC-1a promoter represents the first observation of monoallelic methylation of this gene in early development, and provides further support for a role of canonical Wnt signalling in placental trophoblast invasiveness. This also implicates tumour suppressor gene silencing as an integral part of normal human placental development. PMID:18485586

  9. Human proviral mRNAs down regulated in choriocarcinoma encode a zinc finger protein related to Krüppel.

    PubMed Central

    Kato, N; Shimotohno, K; VanLeeuwen, D; Cohen, M

    1990-01-01

    RNA transcripts of the HERV-R (ERV3) human provirus that are abundant in placenta but absent in choriocarcinoma contain nonproviral genomic sequences at their 3' ends. We report here the isolation of cDNA clones of these genomic sequences. The transcripts encode a Krüppel-related zinc finger protein consisting of a unique leader region and more than 12 28-amino-acid finger motifs. Images PMID:2115127

  10. D21S418E identifies a cAMP-regulated gene located on chromosome 21q22. 3 that is expressed in placental syncytiotrophoblast and choriocarcinoma cells

    SciTech Connect

    Kido, S.; Sakuragi, N.; Bronner, M.P.; Sayegh, R.; Strauss, J.F. III ); Berger, R.; Patterson, D. )

    1993-07-01

    A partial cDNA (D21S418E) whose nucleotide sequence has no significant homologies with known mammalian DNA sequences was isolated from a human placental library. The cDNA hybridized with a 10-kb transcript present in term placenta. Messages of 10 and 7.5 kb were induced in BeWo and JEG-3 choriocarcinoma cells by treatment with 8-Br-cAMP. The mRNA was not detected in human brain, liver, lung, kidney, pancreas, heart, skeletal muscle, or myometrium. The D21S418E locus was assigned to a 3.5-Mb region of chromosome 21q22.3. 15 refs., 2 figs., 1 tab.

  11. Zeranol induces COX-2 expression through TRPC-3 activation in the placental cells JEG-3.

    PubMed

    Zhu, Yun; Yao, Xiaoqiang; Leung, Lai K

    2016-09-01

    Transient Receptor Potential Channels (TRPs) are commonly expressed in the reproductive tissues in human. Many female reproductive processes have been associated with these TRPs. The mycotoxin zeranol or α-zearalanol is derived from fungi in the Fusarium family. Limited exposure to zeranol appears to be safe. In North America, farmers are using synthetic zeranol to promote growth in livestock. As the health risks of exposure to residual zeranol have not been determined, this practice is disallowed in the European Community. In the present study the cellular calcium levels were elevated in JEG-3 cells treated with zeranol at or above 10nM. Subsequent study indicated that expressions of TRP channels were induced. In response to the calcium flow, ERK, P38 and PKCβ were activated and COX-2 expression was increased. Specific TRP inhibitors were employed to establish the connection between the ion channel activity and COX-2 expression, and TRPC-3 appeared to be the triggering mechanism. Since the involvement of COX-2 is implicated in placental development and parturition, exposure to this mycotoxin poses a potential threat to pregnant women. PMID:27224899

  12. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    PubMed

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts. PMID:26093985

  13. Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

    PubMed

    Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

    2016-01-01

    Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. PMID:25465476

  14. Apigenin Reduces Survival of Choriocarcinoma Cells by Inducing Apoptosis via the PI3K/AKT and ERK1/2 MAPK Pathways.

    PubMed

    Lim, Whasun; Park, Sunwoo; Bazer, Fuller W; Song, Gwonhwa

    2016-12-01

    Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-proliferative, and anti-spasmodic effects. Based on epidemiological and case-control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti-cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study. Apigenin reduced viability and migratory properties, increased apoptosis, and suppressed mitochondrial membrane potential in both the JAR and JEG3 cells. In addition, apigenin predominantly decreased phosphorylation of AKT, P70RSK, and S6 whereas the phosphorylation of ERK1/2 and P90RSK was increased by apigenin treatment of JAR and JEG3 cells in a dose-dependent manner. Moreover, treatment of JAR and JEG3 cells with both apigenin and pharmacological inhibitors of PI3K/AKT (LY294002) and ERK1/2 (U0126) revealed synergistic anti-proliferative effects. Collectively, these results indicated that the apigenin is an invaluable chemopreventive agent that inhibits progression and metastasis of choriocarcinoma cells through regulation of PI3K/AKT and ERK1/2 MAPK signal transduction mechanism. J. Cell. Physiol. 231: 2690-2699, 2016. © 2016 Wiley Periodicals, Inc. PMID:26970256

  15. Choriocarcinoma presenting with thyrotoxicosis

    PubMed Central

    Sotello, David; Test, Victor J.; Lado-Abeal, Joaquin

    2016-01-01

    We describe a 26-year-old man with metastatic choriocarcinoma who presented with hyperthyroidism associated with elevated β-human chorionic gonadotropin (B-HCG) and respiratory failure secondary to diffuse lung metastasis. After the first cycle of chemotherapy, the concentration of B-HCG dramatically decreased and the patient became euthyroid, allowing us to discontinue antithyroid medications. The patient's hyperthyroidism was caused by stimulation of the thyroid gland by high B-HCG levels, as shown by the marked improvement of the patient's thyroid function panel after chemotherapy. PMID:26722165

  16. Choriocarcinoma presenting with thyrotoxicosis.

    PubMed

    Sotello, David; Rivas, Ana Marcella; Test, Victor J; Lado-Abeal, Joaquin

    2016-01-01

    We describe a 26-year-old man with metastatic choriocarcinoma who presented with hyperthyroidism associated with elevated β-human chorionic gonadotropin (B-HCG) and respiratory failure secondary to diffuse lung metastasis. After the first cycle of chemotherapy, the concentration of B-HCG dramatically decreased and the patient became euthyroid, allowing us to discontinue antithyroid medications. The patient's hyperthyroidism was caused by stimulation of the thyroid gland by high B-HCG levels, as shown by the marked improvement of the patient's thyroid function panel after chemotherapy. PMID:26722165

  17. Choriocarcinoma: blocking factor and monoclonal antibody iodine 131 imaging

    SciTech Connect

    Pattillo, R.A.; Khazaeli, M.B.; Ruckert, A.C.; Hussa, R.O.; Collier, B.D.; Beierwaltes, W.; Mattingly, R.F.

    1984-04-01

    Postoperative iodine 131 monoclonal antibody localization in metastatic choriocarcinoma was accomplished in this study. The monoclonal antibody was prepared to male choriocarcinoma which cross reacted with gestational choriocarcinoma. The antibody was raised against whole choriocarcinoma cells and human chorionic gonadotropin (hCG) cross reactivity was excluded. The purified antibody was iodinated with /sup 131/I and successfully imaged BeWo choriocarcinoma transplanted in nude mice; however, imaging of choriocarcinoma in a patient was verified only after resection. It is our belief that failure to sufficiently concentrate the antibody in the tumor before operation was due to blocking factor in the serum of the patient. Blocking factor and hCG dropped postoperatively. Blocking factor activity in 15 patients with metastatic trophoblastic disease was monitored and, like hCG, was found to be a sensitive indicator of the presence of disease. Its efficacy may be in the small number of patients without hCG but with persistent disease.

  18. Nimbolide a limonoid from Azadirachta indica inhibits proliferation and induces apoptosis of human choriocarcinoma (BeWo) cells.

    PubMed

    Harish Kumar, G; Chandra Mohan, K V P; Jagannadha Rao, A; Nagini, S

    2009-06-01

    We investigated the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree (Azadirachta indica) on human choriocarcinoma (BeWo) cells. Treatment with nimbolide resulted in dose- and time-dependent inhibition of growth of BeWo cells with IC(50) values of 2.01 and 1.19 microM for 7 and 24 h respectively, accompanied by downregulation of proliferating cell nuclear antigen. Examination of nuclear morphology revealed fragmentation and condensation indicating apoptosis. Increase in the generation of reactive oxygen species (ROS) that was reversed by addition of reduced glutathione suggested ROS involvement in the cytotoxicity of nimbolide. A decrease in Bcl-2/Bax ratio with increased expression of Apaf-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase provide compelling evidence that nimbolide-induced apoptosis is mediated by the mitochondrial pathway. The results of the present study suggest that nimbolide has immense potential in cancer prevention and therapy based on its antiproliferative and apoptosis inducing effects. PMID:18719855

  19. Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line.

    PubMed

    Liu, A-X; Zhang, D; Zhu, Y-M; Gao, H-J; Jiang, J-Y; Hu, X-L; Lv, P-P; Leung, P C K; Huang, H-F

    2016-01-01

    Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental and JEG-3 cell function. Furthermore, we aim to investigate the downstream pathways of GHRH/GHRH-R axis in the control of the JEG-3 cell viability and apoptosis. In this study, we detected the expression pattern of GHRH-R in human chorionic villous tissues and JEG-3 cell. Then, we evaluated the effects of GHRH/GHRH-R and the downstream pathways by using GHRH antagonist (JMR-132) on JEG-3 cell. Our present study found the expressions of GHRH-R in placental villous tissues and JEG-3 cell, and the expression levels of GHRH-R was significantly lower in villous tissues of early pregnancy loss when compared to normal controls. JMR-132 inhibited cellular viability and induced apoptosis in JEG-3 cell in a time and dosedependent manners through activation of caspase-3, p38, and p53, as well as inhibition of phosphorylation of Akt. Interestingly, ER stress markers such as GRP78, ubiquitinated proteins and phospho-eIF2α were significantly increased in JEG-3 cell after being treated with JMR-132. Conversely, pretreated with salubrinal (a selective inhibition of protein phosphatase 1-mediated eIF2α dephosphorylation), JEG-3 cells were rescued from JMR-132-mediated cell growth inhibition, and abolished JMR-132-induced cleaved caspase-3, CHOP, phospho-p53, and ubiquitinated proteins accumulation. Knockdown of endogenous GHRH-R significantly abolished the JMR-132-induced cleaved caspase-3 and activation of p38. In conclusion, our results, for the first time, demonstrated the expression levels of GHRH-R were closely related to the placental function. Inhibition of GHRH-R by using GHRH antagonist in JEG-3 cell may reduce cell viability and induce apoptosis through

  20. A Successfully Treated Metastatic Choriocarcinoma Coexistent With Pregnancy

    PubMed Central

    Yu, Panxi; Diao, Wenqi; Jiang, Xuefeng

    2016-01-01

    Abstract Gestational choriocarcinoma ended with a successful parturition is extremely rare, especially in cases where multiple metastases occurred. A 29-year-old Chinese primigravida was admitted with vaginal bleeding at 32+2 gestational week, and diagnosed with gestational choriocarcinoma with vaginal, pulmonary, and cerebral metastasis after pathological, and imaging examination. At 33+1 gestational week, a healthy infant was delivered by cesarean section. Although no evidence of choriocarcinoma or any other forms of gestational trophoblastic diseases was found in the placenta and uterine curettages, the patient was given 7 cycles of postpartum chemotherapy. Her serum beta-human chorionic gonadotropin level fell to the normal range, and the metastatic lesions reduced. The baby is still free from diseases, and the patient reports no clinical manifestation 4 years after the hospital discharge. Despite its rapid metastases and complications, gestational choriocarcinoma still can be successfully treated by postpartum chemotherapy with the least delay. PMID:27227917

  1. Squelching of ETS2 transactivation by POU5F1 silences the human chorionic gonadotropin CGA subunit gene in human choriocarcinoma and embryonic stem cells.

    PubMed

    Gupta, Rangan; Ezashi, Toshihiko; Roberts, R Michael

    2012-05-01

    The subunit genes encoding human chorionic gonadotropin, CGA, and CGB, are up-regulated in human trophoblast. However, they are effectively silenced in choriocarcinoma cells by ectopically expressed POU domain class 5 transcription factor 1 (POU5F1). Here we show that POU5F1 represses activity of the CGA promoter through its interactions with ETS2, a transcription factor required for both placental development and human chorionic gonadotropin subunit gene expression, by forming a complex that precludes ETS2 from interacting with the CGA promoter. Mutation of a POU5F1 binding site proximal to the ETS2 binding site does not alter the ability of POU5F1 to act as a repressor but causes a drop in basal promoter activity due to overlap with the binding site for DLX3. DLX3 has only a modest ability to raise basal CGA promoter activity, but its coexpression with ETS2 can up-regulate it 100-fold or more. The two factors form a complex, and both must bind to the promoter for the combination to be transcriptionally effective, a synergy compromised by POU5F1. Similarly, in human embryonic stem cells, which express ETS2 but not CGA, ETS2 does not occupy its binding site on the CGA promoter but is found instead as a soluble complex with POU5F1. When human embryonic stem cells differentiate in response to bone morphogenetic protein-4 and concentrations of POU5F1 fall and hCG and DLX3 rise, ETS2 then occupies its binding site on the CGA promoter. Hence, a squelching mechanism underpins the transcriptional silencing of CGA by POU5F1 and could have general relevance to how pluripotency is maintained and how the trophoblast lineage emerges from pluripotent precursor cells. PMID:22446105

  2. The molecular role of connexin 43 in human trophoblast cell fusion.

    PubMed

    Dunk, Caroline E; Gellhaus, Alexandra; Drewlo, Sascha; Baczyk, Dora; Pötgens, Andy J G; Winterhager, Elke; Kingdom, John C P; Lye, Steven J

    2012-04-01

    Connexin expression and gap junctional intercellular communication (GJIC) mediated by connexin 43 (Cx43)/gap junction A1 (GJA1) are required for cytotrophoblast fusion into the syncytium, the outer functional layer of the human placenta. Cx43 also impacts intracellular signaling through protein-protein interactions. The transcription factor GCM1 and its downstream target ERVW-1/SYNCYTIN-1 are key players in trophoblast fusion and exert their actions through the ERVW-1 receptor SLC1A5/ASCT-2/RDR/ATB(0). To investigate the molecular role of the Cx43 protein and its interaction with this fusogenic pathway, we utilized stable Cx43-transfected cell lines established from the choriocarcinoma cell line Jeg3: wild-type Jeg3, alphahCG/Cx43 (constitutive Cx43 expression), JpUHD/Cx43 (doxycyclin-inducible Cx43 expression), or JpUHD/trCx43 (doxycyclin-inducible Cx43 carboxyterminal deleted). We hypothesized that truncation of Cx43 at its C-terminus would inhibit trophoblast fusion and protein interaction with either ERVW-1 or SLC1A5. In the alphahCG/Cx43 and JpUHD/Cx43 lines, stimulation with cAMP caused 1) increase in GJA1 mRNA levels, 2) increase in percentage of fused cells, and 3) downregulation of SLC1A5 expression. Cell fusion was inhibited by GJIC blockade using carbenoxylone. Neither Jeg3, which express low levels of Cx43, nor the JpUHD/trCx43 cell line demonstrated cell fusion or downregulation of SLC1A5. However, GCM1 and ERVW-1 mRNAs were upregulated by cAMP treatment in both Jeg3 and all Cx43 cell lines. Silencing of GCM1 prevented the induction of GJA1 mRNA by forskolin in BeWo choriocarcinoma cells, demonstrating that GCM1 is upstream of Cx43. All cell lines and first-trimester villous explants also demonstrated coimmunoprecipitation of SLC1A5 and phosphorylated Cx43. Importantly, SLC1A5 and Cx43 gap junction plaques colocalized in situ to areas of fusing cytotrophoblast, as demonstrated by the loss of E-cadherin staining in the plasma membrane in first

  3. Retained Placenta Accreta Mimicking Choriocarcinoma

    PubMed Central

    Kohi, Maureen P.; Rizzuto, Gabrielle A.; Fidelman, Nicholas; Lucero, Jennifer; Thiet, Mari-Paule

    2015-01-01

    This case demonstrates a rare event of retained invasive placenta masquerading as choriocarcinoma. The patient presented with heavy vaginal bleeding following vaginal delivery complicated by retained products of conception. Ultrasound and computed tomography demonstrated a vascular endometrial mass, invading the uterine wall and raising suspicion for choriocarcinoma. Hysterectomy revealed retained invasive placenta. PMID:26495146

  4. Primary choriocarcinoma of appendix mimicking acute appendicitis.

    PubMed

    Khan, Enam Murshed; Chakrabarti, Amrita; Dwary, Amit Dutt

    2015-01-01

    Choriocarcinoma is a malignant trophoblastic cancer, the incidence of primary choriocarcinoma (PCC) of the gastrointestinal tract (GIT) being extremely rare, with only 14 cases being reported in worldwide literature. Here we present an extremely rare case of PCCof the appendix in a 32-year-old male who presented with acute pain abdomen. Histopathological examination revealed PCC of the appendix. Examination of the testis was unremarkable. Further investigations revealed a very high serum beta-human chorionic gonadotropin (b-HCG) titer with a normal carcinoembryonic antigen (CEA). Radiological imaging showed multiple areas of liver metastasis. Chemotherapy-based treatment with bleomycin, etoposide, and cisplatin (BEP) regime was advised, however the patient failed to follow-up for further management. PMID:26881617

  5. Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG.

    PubMed

    Kovalevskaya, G; Birken, S; Kakuma, T; O'Connor, J F

    1999-04-01

    Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome. PMID:10194533

  6. Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.

    PubMed

    Wittmaack, F M; Gåfvels, M E; Bronner, M; Matsuo, H; McCrae, K R; Tomaszewski, J E; Robinson, S L; Strickland, D K; Strauss, J F

    1995-01-01

    The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) family. Very little is known about VLDLR localization and regulation. Immunohistochemical analysis of human placenta with a specific polyclonal antibody detected VLDLR in syncytiotrophoblast and intermediate trophoblast cells. VLDLR transcripts were also localized in these cells by in situ hybridization histochemistry. In addition, VLDLR messenger RNA (mRNA) was detected in villous core endothelial cells and cells appearing to be Hofbauer cells. Northern blot analysis of placenta revealed a 2.6-fold increase in VLDLR mRNA at term compared to that in the first trimester. The regulation of VLDLR expression was studied in JEG-3 and BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Treatment of these cells with 8-bromo-cAMP caused a profound suppression of VLDLR message, whereas LDLR transcripts were increased. Incubation of JEG-3 cells with 25-hydroxycholesterol did not lead to sterol negative feedback on VLDLR gene expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up-regulated VLDLR message in JEG-3 cells 2-fold, as did the fibrate hypolipidemic drug, clofibric acid. We conclude that 1) VLDLR is expressed in human placental trophoblast cells in a pattern consistent with a role in placental lipid transport; 2) VLDLR expression is high at term relative to that in the first trimester; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and up-regulation by insulin and fibrate hypolipidemic drugs. PMID:7828550

  7. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    SciTech Connect

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  8. Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down.

    PubMed

    Hogg, K; Robinson, W P; Beristain, A G

    2014-07-01

    Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 μM 5-Aza-2'-deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by ∼30-50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P < 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated ∼40-fold in response to 5-Aza-CdR exposure in BeWo cells (P < 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data. PMID:24623739

  9. A Successfully Treated Metastatic Choriocarcinoma Coexistent With Pregnancy: A Case Report of a 4-Year Follow-Up.

    PubMed

    Yu, Panxi; Diao, Wenqi; Jiang, Xuefeng

    2016-05-01

    Gestational choriocarcinoma ended with a successful parturition is extremely rare, especially in cases where multiple metastases occurred.A 29-year-old Chinese primigravida was admitted with vaginal bleeding at 32 gestational week, and diagnosed with gestational choriocarcinoma with vaginal, pulmonary, and cerebral metastasis after pathological, and imaging examination. At 33 gestational week, a healthy infant was delivered by cesarean section. Although no evidence of choriocarcinoma or any other forms of gestational trophoblastic diseases was found in the placenta and uterine curettages, the patient was given 7 cycles of postpartum chemotherapy. Her serum beta-human chorionic gonadotropin level fell to the normal range, and the metastatic lesions reduced. The baby is still free from diseases, and the patient reports no clinical manifestation 4 years after the hospital discharge.Despite its rapid metastases and complications, gestational choriocarcinoma still can be successfully treated by postpartum chemotherapy with the least delay. PMID:27227917

  10. Choriocarcinoma

    MedlinePlus

    ... in the tissue that would normally become the placenta. This is the organ that develops during pregnancy ... include: Quantitative serum HCG Complete blood count Kidney function tests Liver function tests Imaging tests that may ...

  11. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

    PubMed Central

    Gunduz, Seyda; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; Bozcuk, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein. PMID:23525369

  12. Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes.

    PubMed Central

    Sanderson, J T; Letcher, R J; Heneweer, M; Giesy, J P; van den Berg, M

    2001-01-01

    We investigated a potential mechanism for the estrogenic properties of three chloro-s-triazine herbicides and six metabolites in vitro in several cell systems. We determined effects on human aromatase (CYP19), the enzyme that converts androgens to estrogens, in H295R (adrenocortical carcinoma), JEG-3 (placental choriocarcinoma), and MCF-7 (breast cancer) cells; we determined effects on estrogen receptor-mediated induction of vitellogenin in primary hepatocyte cultures of adult male carp (Cyprinus carpio). In addition to atrazine, simazine, and propazine, two metabolites--atrazine-desethyl and atrazine-desisopropyl--induced aromatase activity in H295R cells concentration-dependently (0.3-30 microM) and with potencies similar to those of the parent triazines. After a 24-hr exposure to 30 microM of the triazines, an apparent maximum induction of about 2- to 2.5-fold was achieved. The induction responses were confirmed by similar increases in CYP19 mRNA levels, determined by reverse-transcriptase polymerase chain reaction. In JEG-3 cells, where basal aromatase expression is about 15-fold greater than in H295R cells, the induction responses were similar but less pronounced; aromatase expression in MCF-7 cells was neither detectable nor inducible under our culture conditions. The fully dealkylated metabolite atrazine-desethyl-desisopropyl and the three hydroxylated metabolites (2-OH-atrazine-desethyl, -desisopropyl, and -desethyl-desisopropyl) did not induce aromatase activity. None of the triazine herbicides nor their metabolites induced vitellogenin production in male carp hepatocytes; nor did they antagonize the induction of vitellogenin by 100 nM (EC(50) 17beta-estradiol. These findings together with other reports indicate that the estrogenic effects associated with the triazine herbicides in vivo are not estrogen receptor-mediated, but may be explained partly by their ability to induce aromatase in vitro. PMID:11675267

  13. The C-terminal domain of the nuclear factor I-B2 isoform is glycosylated and transactivates the WAP gene in the JEG-3 cells

    SciTech Connect

    Mukhopadhyay, Sudit S. . E-mail: suditmukhopadhy@yahoo.com; Rosen, Jeffrey M. . E-mail: jrosen@bcm.tmc.edu

    2007-07-06

    The transcription factor nuclear factor I (NFI) has been shown previously both in vivo and in vitro to be involved in the cooperative regulation of whey acidic protein (WAP) gene transcription along with the glucocorticoid receptor and STAT5. In addition, one of the specific NFI isoforms, NFI-B2, was demonstrated in transient co-transfection experiments in JEG cells, which lack endogenous NFI, to be preferentially involved in the cooperative regulation of WAP gene expression. A comparison of the DNA-binding specificities of the different NFI isoforms only partially explained their differential ability to activate the WAP gene transcription. Here, we analyzed the transactivation regions of two NFI isoforms by making chimeric proteins between the NFI-A and B isoforms. Though, their DNA-binding specificities were not altered as compared to the corresponding wild-type transcription factors, the C-terminal region of the NFI-B isoform was shown to preferentially activate WAP gene transcription in cooperation with GR and STAT5 in transient co-transfection assays in JEG-3 cells. Furthermore, determination of serine and threonine-specific glycosylation (O-linked N-acetylglucosamine) of the C-terminus of the NFI-B isoform suggested that the secondary modification by O-GlcNAc might play a role in the cooperative regulation of WAP gene transcription by NFI-B2 and STAT5.

  14. Abnormal Presentation of Choriocarcinoma and Literature Review

    PubMed Central

    Yousefi, Zohreh; Mottaghi, Mansorhe; Rezaei, Alireza; Ghasemian, Sedighe

    2016-01-01

    Introduction Gestational trophoblastic neoplasms have highly been malignant potential, which usually occurred in child-bearing age women. Unusual feature of this malignancy would be rare, it was important to take in mind the possibility of GTN in different manifestation. Based on the above mentioned, the aim of this presentation would be the management and outcome of a case series of choriocarcinoma patients with abnormal manifestation. Case Presentation We have presented four patients, first who initially manifestation with signs of septic shock, the second case with severe gastrointestinal hemorrhage, the third case with postpartum infection and the forth case was a postmenopausal bleeding patient. Conclusions In case of metastatic choriocarcinoma with precise history, accurate diagnosis and appropriate treatment have led us to curable results. PMID:27482332

  15. Primary Intracranial Choriocarcinoma Located in the Suprasellar Region

    PubMed Central

    Li, Xiuli; Murayama, Kazuhiro; Watanabe, Ayumi; Abe, Masato; Toyama, Hiroshi

    2016-01-01

    A 10 year old girl was admitted to our hospital due to headache, nausea, and weight loss for about half a year. She also had visual field disorders. Suprasellar tumor was found by X-ray computed tomography, and magnetic resonance imaging showed a ring-like lobulated enhanced mass with hemorrhage and necrosis. Biopsy of this lesion showed primary intracranial choriocarcinoma on histopathological examination. The serum human chorionic gonadotropin (hCG) level was measured after the biopsy and was elevated at 71,298.2 IU/L. The patient died due to hydrocephalus caused by an increase in the size of the tumor with a larger amount of hemorrhage than the preoperative features. If young patients present with a suprasellar lobulated mass with hemorrhage, the serum hCG level should be measured before operation. PMID:27499824

  16. [Chemotherapy-sensitive uterine choriocarcinoma: a case report].

    PubMed

    Dimitrakova, E; Pekhlivanov, B; Milchev, N

    2009-01-01

    We report a case of uterine choriocarcinoma in a 42-year-old female presenting with abdominal pain, uterus enlargement, high serum levels of beta human chorionic gonadotropin (b-hCG) and a positive pregnancy test on two separate occasions. At laparatomy, blood and clots were observed in the abdomen, an enlarged uterus with tumor infiltrates in the uterus, appendix, bladder and plica vesico-uterina. Follwing hysterectomy and bilateral oophoorectomy, the patient received chemotherapy and was followed for two years. No tumor recurrences were observed and the b-hCG levels returned to normal. In conclusion, the condition responds favorably the chemotherapy and recurrences are rate when there are no metastases to the liver or the brain. PMID:20198788

  17. Primary renal artery choriocarcinoma causing secondary renovascular hypertension

    PubMed Central

    Usta, Taner Abdullah; Karacan, Tolga; Ozyurek, Eser; Naki, M. Murat; Omeroglu, Suat Nail; Demirkiran, Fuat

    2014-01-01

    INTRODUCTION Choriocarcinoma is a rare primary germ cell tumour of the ovary composed of cyto- and syncytotrophoblast cells. Most of the choriocarcinomas are normally arising in the gestational trophoblast, gonads and, less frequently, mediastinum, pineal gland and retroperitoneum. PRESENTATION OF CASE We report a case of primary choriocarcinoma of renal artery causing secondary renovascular hypertension in a 28 years old woman of reproductive age, presenting with abdominal pain, minimal vaginal bleeding and a delayed menstrual period. DISCUSSION Non-gestational choriocarcinomas, are histologically related to the pregnancy related gestational choriocarcinomas. These two subtypes may have to be differentiated according the clinical and radiological findings and DNA analysis may be used for this purpose as well. In many studies, authors have stated that nongestational choriocarcinoma diagnosis could be implemented in situations where the presence of a pregnancy could not be considered like the prepubertal period. CONCLUSION Choriocarcinoma should as well be considered among the possibilities in the differential diagnosis of the causes for secondary hypertension, especially within a picture of pregnancy of unknown location, albeit being one of the rarest. PMID:25437675

  18. Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma.

    PubMed

    Alturkistani, Husain; Almarzooqi, Mohamed-Karji; Oliva, Vincent; Gilbert, Patrick

    2016-01-01

    This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life-threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma. PMID:27403360

  19. Arteriovenous Fistula Embolization in Suspected Parauterine Choriocarcinoma

    PubMed Central

    Almarzooqi, Mohamed-Karji; Oliva, Vincent; Gilbert, Patrick

    2016-01-01

    This is a case of choriocarcinoma that did not regress after chemotherapy treatment. A 30-year-old female patient (gravida 2, para 2), presented to our ER with stroke and persistent mild pelvic pain 2 months after a Caesarean section. Computed tomography (CT) revealed an ischemic left hemicerebellar region and a hypervascular mass in the pelvic region. This mass was not present on routine fetal ultrasound during pregnancy. The lesion was treated by chemotherapy after closure of a foramen ovale and insertion of an inferior vena cava (IVC) filter. After that, 2 courses of EMACO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide, and Vincristine) chemotherapy regimen were given. Posttreatment CT showed the hypervascular mass without any changes. Arteriography showed the arteriovenous fistulae that were embolized successfully with plugs, coils, and glue. Embolization was considered due to the risk of acute hemorrhagic life-threatening complications. Eight chemotherapy courses were added after embolization. Treatment by endovascular approach and reduction of the hypervascular mass can be a valuable adjunct to chemotherapy treatment of choriocarcinoma. PMID:27403360

  20. A rare case of primary choriocarcinoma in the sigmoid colon.

    PubMed

    Maehira, Hiromitsu; Shimizu, Tomoharu; Sonoda, Hiromichi; Mekata, Eiji; Yamaguchi, Tomoharo; Miyake, Tohru; Ishida, Mitsuaki; Tani, Tohru

    2013-10-21

    Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis. Only 13 cases of colorectal choriocarcinoma have previously been reported. There is no standard chemotherapeutic regimen for this tumor type. A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases. He underwent a laparoscopic sigmoidectomy. Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin. Based on the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) results, mFOLFOX6 and bevacizumab were administered, which suppressed aggressive tumor growth for 4 mo. The patient died 9 mo after the initial diagnosis. Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma. Moreover, CD-DST may provide, at least in part, therapeutic insight for the selection of appropriate antitumor agents for such patients. PMID:24151399

  1. A rare case of primary choriocarcinoma in the sigmoid colon

    PubMed Central

    Maehira, Hiromitsu; Shimizu, Tomoharu; Sonoda, Hiromichi; Mekata, Eiji; Yamaguchi, Tomoharo; Miyake, Tohru; Ishida, Mitsuaki; Tani, Tohru

    2013-01-01

    Primary colorectal choriocarcinoma is an extremely rare neoplasm and is usually associated with a poor prognosis. Only 13 cases of colorectal choriocarcinoma have previously been reported. There is no standard chemotherapeutic regimen for this tumor type. A 68-year-old man presented with melena and was diagnosed with sigmoid colonic adenocarcinoma with multiple liver metastases. He underwent a laparoscopic sigmoidectomy. Pathology revealed choriocarcinoma with a focal component of moderately differentiated adenocarcinoma of colon origin. Based on the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) results, mFOLFOX6 and bevacizumab were administered, which suppressed aggressive tumor growth for 4 mo. The patient died 9 mo after the initial diagnosis. Our study results suggest that the standard chemotherapy regimen for colorectal cancer might have suppressive effects against primary colorectal choriocarcinoma. Moreover, CD-DST may provide, at least in part, therapeutic insight for the selection of appropriate antitumor agents for such patients. PMID:24151399

  2. Pulmonary Metastatic Choriocarcinoma from a Burned-out Testicular Tumor.

    PubMed

    Nakazaki, Hirofumi; Tokuyasu, Hirokazu; Takemoto, Yu; Miura, Hiroshi; Yanai, Masaaki; Fukushima, Takehito; Shimizu, Eiji

    2016-01-01

    A 54-year-old man was referred to our hospital because of progressive dyspnea. Chest computed tomography showed multiple nodular shadows with a peripheral ground-glass halo. His clinical condition continued to deteriorate with the development of progressive respiratory failure requiring mechanical ventilation. A histological examination of a transbronchial lung biopsy revealed choriocarcinoma. The patient died within nine days of admission. A histological examination of the right testis during an autopsy revealed a burned-out testicular tumor consisting of a teratoma and a fibrous scar. We herein report a rare case of pulmonary multiple metastatic choriocarcinoma originating from a burned-out testicular tumor. PMID:27250057

  3. Pure Choriocarcinoma of the Ovary in Silver-Russell Syndrome.

    PubMed

    Haruma, Tomoko; Ogawa, Chikako; Nishida, Takeshi; Kusumoto, Tomoyuki; Nakamura, Keiichiro; Seki, Noriko; Katayama, Takaaki; Hiramatsu, Yuji

    2015-01-01

    Pure ovarian choriocarcinoma is an extremely rare malignancy that can be gestational or non-gestational in origin. Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, a triangular face, hemihypotrophy, and fifth-finger clinodactyly. We report a rare case of pure ovarian choriocarcinoma occurring in a 19-year-old woman with SRS. Following surgery, multiple chemotherapy courses were effective and she was free of disease at the 10-month follow-up. PMID:26101195

  4. Localization of IL-4 and IL-4 receptors in the human term placenta, decidua and amniochorionic membranes.

    PubMed Central

    de Moraes-Pinto, M I; Vince, G S; Flanagan, B F; Hart, C A; Johnson, P M

    1997-01-01

    There has been much recent interest in cytokine expression at the materno-fetal interface. Although T-helper 2 (Th2)-type cytokines have been described in the murine feto-placental unit, few studies have as yet been performed in human pregnancy. We have examined the production of interleukin-4 (IL-4) and expression of IL-4 receptors in the human term placenta, decidua and amniochorionic membranes. Immunohistochemical analyses revealed that cytotrophoblast, decidual macrophages and both maternal and fetal endothelial cells consistently expressed IL-4, whereas syncytiotrophoblast and placental macrophages showed an inconsistent pattern between specimens. High- and low-affinity IL-4 receptors were demonstrated by immunohistochemistry at the same cellular sites as stained for IL-4, and detection of IL-4 receptors was also variable in syncytiotrophoblast. Reverse-transcribed-polymerase chain reaction (RT-PCR) analysis showed that both IL-4 and its alternative splice variant, IL-482, are produced both in placental villi and in amniochorionic and decidual tissue. Ligand-binding assays identified the presence, on isolated term syncytiotrophoblast microvillous plasma membrane vesicle preparations, of functional high-affinity binding sites for IL-4 with a Kd in the range 102-112 pM and an apparent receptor density in the range 99-102 x 10(8) sites/mg protein. Three human choriocarcinoma (BeWo, JEG-3 and Jar) and one amnion-derived (AV3) cell lines expressed IL-4 and both high- and low-affinity IL-4 receptors. The constitutive expression of both IL-4 and IL-4 receptors, together with the novel finding of the alternative splice variant IL-482 in the immediate tissues at the materno fetal interface suggest an immunobiological role for IL-4 in human pregnancy. Images Figure 1 Figure 2 Figure 3 PMID:9038717

  5. Unusual gestational choriocarcinoma arising in an interstitial pregnancy

    PubMed Central

    Meddeb, Sawsen; Rhim, Mohamed Salah; Zarrouk, Wissal; Bibi, Mohamed; Yacoubi, Mohamed Tahar; Khairi, Hedi

    2014-01-01

    INTRODUCTION Choriocarcinoma is a highly malignant trophoblastic neoplasm. Its association with ectopic pregnancy is very rare and usually with aggressive behavior. PRESENTATION OF CASE We report a new case arising in an interstitial pregnancy occurring in a 46-year-old woman. The patient was admitted for severe pelvic pain and abundant metrorrhagia. One month ago, she had had a laparoscopic resection of an interstitial pregnancy subsequent to failure of chemotherapy by methotrexate. The raise of serum βhCG level and the hyperechoic intrauterine mass were in favor of gestational trophoblastic disease. Urgent laparotomy was performed for circulatory collapse. Hysterectomy was done. Histological examination revealed a choriocarcinoma. The patient underwent chemotherapy. Two years later, neither metastasis nor recurrence was detected. DISCUSSION Clinical diagnosis of primary interstitial choriocarcinoma is difficult, since it is rare and manifesting by non-specific abnormal vaginal bleeding. Imaging findings are also not helpful in ectopic location. The frequency of metastasis is related to the delayed diagnosis. Serial measurement of βhCG level was the most useful marker of diagnosis and follow up. Histopathological examination remains the only tool of the precise diagnosis. Choriocarcinoma has a very good prognosis even in advanced stages, since it is very chemosensitive. CONCLUSION The current trend of the treatment of ectopic pregnancy by conservative surgery requires adequate monitoring of βhCG and careful examination of pathologic specimens to avoid misdiagnosis of ectopic gestational trophoblastic disease. PMID:25290382

  6. The Heroes' Journey: A Young Couple's Experience with Choriocarcinoma

    ERIC Educational Resources Information Center

    Marlowe, Dan; Hodgson, Jennifer; Lamson, Angela

    2010-01-01

    A 20 year retrospective qualitative case study was conducted to investigate the relational impact of choriocarcinoma (a type of gestational cancer) on a couple of child-bearing age. A unique feature to the study was that the primary investigator was the couple's biological son, initiating the first known auto-case study design. Using holistic…

  7. Quantification of new antiepileptic drugs by liquid chromatography/electrospray ionization tandem mass spectrometry and its application to cellular uptake experiment using human placental choriocarcinoma BeWo cells.

    PubMed

    Furugen, Ayako; Kobayashi, Masaki; Nishimura, Ayako; Takamura, Shigeo; Narumi, Katsuya; Yamada, Takehiro; Iseki, Ken

    2015-10-01

    A method for quantification of new antiepileptic drugs, including lamotrigine (LTG), levetiracetam (LEV), gabapentin (GBP), and topiramate (TPM), in cellular samples, using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to better understand the membrane transport mechanisms of these drugs. Cell lysate was deproteinized by methanol containing LEV-d3 as an internal standard (IS). Chromatographic separation was performed on a C18 column using gradient elution with methanol-water-formic acid (10:90:0.1, v/v/v) and methanol-formic acid (100:0.1, v/v). Analytes were detected in positive ion electrospray mode with selected reaction monitoring (SRM). This method was applicable for a linear range of 5 to 500pmol for LTG; 5 to 1000pmol for LEV; 10 to 10,000pmol for GBP; and 5 to 5000pmol for TPM. The intra-day precision, inter-day precision, and accuracy data were assessed and found to be acceptable. This developed and validated method was then successfully applied to the investigation of uptake of the new antiepileptic drugs in placental choriocarcinoma BeWo cells. The intracellular concentration of these drugs in BeWo cells, accumulating over 30min at 37°C was in the order of GBP>LTG>LEV≈TPM. Furthermore, the uptake of GBP at 4°C was much lower than that at 37°C. The uptake of GBP was saturated at high concentrations. The kinetic parameters calculated for GBP uptake in BeWo cells were determined as Km of 105.4±6.4μM and Vmax at 8153±348pmol/mg protein/min. The novel method described here should enable investigators to elucidate the transport mechanisms of these antiepileptic drugs in BeWo cells. PMID:26343016

  8. Cytomorphology of lung metastasis of pure choriocarcinoma of testis in a 58-year-old male.

    PubMed

    Puri, Shailja; Sood, Shivani; Mohindroo, Shobha; Kaushal, Vijay

    2015-01-01

    Choriocarcinoma is malignancy arising from the trophoblastic tissue. Pure choriocarcinoma is rare in testis. Choriocarcinoma of testis is more commonly associated with other germ cell tumors. The usual age of presentation is 2nd-3rd decade. Distant metastasis is known to occur in choriocarcinoma. We present a rare case of testicular pure choriocarcinoma in a male patient. The patient was treated with orchidectomy, lymphadenectomy, and chemotherapy. Three months later the patient presented with hemoptysis and a lung mass. The aspiration cytology of the lung mass revealed metastatic deposits of syncytiotrophoblastic and cytiotrophoblastic cells. We are reporting this case due to its rarity, rare age of presentation, and characteristic cytology at metastatic focus. PMID:26881635

  9. Galectin signature of the choriocarcinoma JAr cells: Galectin-1 as a modulator of invasiveness in vitro.

    PubMed

    Kolundžić, Nikola; Ćujić, Danica; Abu Rabi, Tamara; Bojić-Trbojević, Žanka; Kadoya, Toshihiko; Vićovac, Ljiljana

    2015-10-01

    Our previous findings showed that galectin-1 (LGALS1) plays an important role in the in vitro invasion of normal human trophoblast cells. In the present study, choriocarcinoma JAr cells were found to express LGALS1, -2, -3, -8, -10, and -13 mRNA and at least LGALS1, -3, and -8 protein, as determined by reverse-transcriptase PCR and Western blot, respectively. The galectin mRNA signature of JAr cells thus differed from that of normal first-trimester extravillous trophoblasts. A Matrigel migration assay was also used to investigate and confirm the relevance and effect of LGALS1 on the invasive potential of JAr cells, as observed in other trophoblast models. This modulation in behavior was achieved by specific lectin-glycan binding. PMID:26096842

  10. [Metastatic choriocarcinoma associated with Wunderlich syndrome: case report and literature review].

    PubMed

    Ojendiz-Nava, Roberto Carlos; Niebla-Cárdenas, Danniela; Hernández-Flores, Sara Elia; Audifred-Salomón, Jorge Román; Morales-Leyte, Ana Lilia

    2015-03-01

    Choriocarcinoma is a rare condition, with an incidence of 1 in 30 to 40,000 pregnancies in the United States and Europe. In Mexico it is reported in 1 in 10,000 pregnancies. Wunderlich syndrome is a spontaneous perirenal hematoma, a very rare entity. This paper reports the case of a young patient with a history of molar pregnancy one year prior to admission, valuation due to fainting, generalized headache, spontaneous pain in the right flank and data of hypovolemic shock. Computed tomography reported right perirenal hematoma, normal uterus, two annexes with data of tecaluteinic cysts, beta human chorionic gonadotropin greater than 200,000 IU/mL. Patient was stabilized with crystalloid, blood products and right adrenal artery embolization. It was corroborated the brain, mediastinum and abdomen metastases. She was sent to a third level hospital, starting holocraneal radiotherapy, she had retroperitoneal bleeding and died a week later. PMID:26058172

  11. A pure non-gestational ovarian choriocarcinoma with delayed solitary brain metastases: Case report and review of the literature.

    PubMed

    Rao, K V L Narasinga; Konar, Subhas; Gangadharan, Jagathlal; Vikas, V; Sampath, S

    2015-01-01

    Choriocarcinoma is the most malignant tumour of gestational trophoblastic origin. Most ovarian choriocarcinomas are gestational in origin and usually metastasize to the ovary from uterine or tubal choriocarcinoma. Non gestational choriocarcinoma (NGOC) of the ovary is exceedingly rare and usually seen along with other germ cell tumors. Non gestational choriocarcinoma has been found to be resistant to single-agent chemotherapy and has a worse prognosis than gestational choriocarcinoma. We are reporting long term follow up of published rare case of pure non gestational ovarian choriocarcinoma (NGOC) with concurrent metastases to the spleen and adrenal glands, who developed a delayed solitary brain metastases, two years after completion of primary treatment. Surgery along with triple agent chemotherapy and radiotherapy was found to give good remission in this aggressive disease. PMID:26752905

  12. Biochemical remission by chemoradiotherapy in male mediastinal choriocarcinoma with diffuse lung metastasis: A case report

    PubMed Central

    ZHANG, JING; WANG, ZHI-JUN; YANG, BIN; WEI, YOU-YING; YANG, LING; HU, YANG; HU, YAN-PING

    2016-01-01

    Primary mediastinal choriocarcinoma is a rare malignancy that is characterized by multiple metastases at the time of diagnosis, poor response to therapy and short survival times. There is no standard treatment for this disease. The present study described the case of a 25-year-old man with metastatic mediastinal choriocarcinoma. The patient completed 8 cycles of standard combination chemotherapy consisting of etoposide [100 mg/m2; intravenous (IV) drip on days 1–3], cisplatin (20 mg/m2; IV drip on days 1–5) and bleomycin (20 mg/m2; intramuscular injection on days 1, 8 and 15 every 21 days). The α-fetoprotein level decreased to 2.36 ng/ml, the serum β-human chorionic gonadotropin (β-HCG) level markedly decreased to 8.69 IU/l, which was slightly higher than the normal upper limit, and the lactate dehydrogenase level decreased to a normal range. The computed tomography (CT) scan revealed that the number and size of the lung lesions was significantly reduced subsequent to 8 cycles of chemotherapy and the size of the mediastinal tumor was evidently reduced, with a less solid component and a more cystic component. The response assessment indicated partial remission. Following chemotherapy, a radiation dose of 50 Gy (2.0 Gy/fraction) was administered to the involved field of the mediastinum. Following radiotherapy, the β-HCG level had also decreased to normal levels, and CT evaluation revealed that the size of the residual lung lesions demonstrated no evident change, and the mediastinal tumor was slightly reduced in size, with a less solid component. The patient refused to undergo surgery and did not receive additional treatment following radiotherapy. At present, the patient has survived >16 months of follow-up without any symptoms. PMID:27073527

  13. FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review.

    PubMed

    Ma, Naili; Litkouhi, Babak; Mannion, Ciaran M

    2016-03-01

    A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX[12]. The patient's serum β-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum β-human chorionic gonadotropin level has remained consistently below detectable levels. PMID:26352546

  14. SALL4 expression in gestational trophoblastic tumors: a useful tool to distinguish choriocarcinoma from placental site trophoblastic tumor and epithelioid trophoblastic tumor.

    PubMed

    Stichelbout, Morgane; Devisme, Louise; Franquet-Ansart, Hélène; Massardier, Jérôme; Vinatier, Denis; Renaud, Florence; Kerdraon, Olivier

    2016-08-01

    SALL4 has important functions in embryonic stem cells. The aim of this study was to investigate SALL4 expression in gestational trophoblastic neoplasia. We hypothesized that it could help to distinguish choriocarcinoma, the presumed most primitive form of gestational trophoblastic neoplasia, from placental site trophoblastic tumor and epithelioid trophoblastic tumor, which would be more differentiated variants. This study included 31 gestational trophoblastic neoplasias: 19 choriocarcinomas, 9 placental site trophoblastic tumors, 1 epithelioid trophoblastic tumor, and 2 mixed tumors comprising a placental site trophoblastic tumor and an epithelioid trophoblastic tumor. Unlike usual markers of gestational trophoblastic neoplasia (p63, human chorionic gonadotrophin and human placental lactogen), SALL4 was expressed in 100% of choriocarcinomas and it was not detected in any placental site trophoblastic tumor and epithelioid trophoblastic tumor. However, the proportion of positive cells varied in a wide range, from 10% to 70%, reflecting the fact that SALL4 was specifically present in mononuclear cells consistent with neoplastic cytotrophoblast. So, SALL4 may be helpful in the differential diagnosis of gestational trophoblastic neoplasias. PMID:27068524

  15. The uterine choriocarcinoma in postmenopausal women: specificities of diagnosis and treatment

    PubMed Central

    Kaabia, Ons; Meddeb, Sawsen; Rhim, Mohamed Salah; Bibi, Mohamed; Khairi, Hedi

    2014-01-01

    Choriocarcinoma is a gestational trophoblastic tumor that mainly affects women of childbearing age. Cases of choriocarcinoma in postmenopausal women are exceptional. Through an observation and literature review, we propose to study the specific diagnosis and treatment features of this tumor in menopausal women. We report the observation of a pure uterine choriocarcinoma, which occurred in post-menopause. The diagnosis was made on the analysis of surgical specimens confirmed by measurement of hCG. Chemotherapy was started after a total hysterectomy and bilateral salpingo-oophorectomy first. The improvement was dramatic after 3 courses of chemotherapy and the patient is in complete remission after five years of monitoring. The primitive forms of pure choriocarcinoma in postmenopausal women are exceptional. Their etiology is poorly understood and their treatment based on chemotherapy. PMID:25815097

  16. A case of metastatic testicular cancer complicated by tumour lysis syndrome and choriocarcinoma syndrome.

    PubMed

    Kawai, Koji; Takaoka, Ei-Ichiro; Naoi, Makito; Mori, Kensaku; Minami, Manabu; Shimazui, Toru; Akaza, Hideyuki

    2006-10-01

    A 26-year-old man was referred to our hospital for treatment of metastatic testicular cancer. The pathological diagnosis was choriocarcinoma with seminoma. Sequential computerized tomography examinations revealed rapidly progressing bulky liver metastases and a lung metastasis. Chemotherapy with bleomycin, etoposide and cisplatin (BEP) was started on the day of admission. Subsequently, the patient suffered from tumour lysis syndrome (TLS) and massive haemorrhage at metastatic sites. The latter complication is also called choriocarcinoma syndrome. To our knowledge, this is the first case report of testicular cancer complicated with both critical conditions. Intensive care and radiological intervention barely prevented a fatal outcome. The urological oncologist should be aware of the potential complications TLS and choriocarcinoma syndrome in cases of rapidly progressive and high-volume choriocarcinoma. PMID:16935862

  17. Massive Fetomaternal Hemorrhage Caused by an Intraplacental Choriocarcinoma: A Case Report

    PubMed Central

    Henningsen, Anna-Karina Aaris; Maroun, Lisa Leth; Havsteen, Hanne; Svare, Jens

    2010-01-01

    Background. Intraplacental choriocarcinoma is a rare but highly malignant trophoblastic neoplasm. When found near term the risk of maternal metastasis is high because of the late diagnosis. Case. We describe a case of an intraplacental choriocarcinoma diagnosed postpartum after a near-term delivery of a severely anemic infant. A fetomaternal hemorrhage resulted in a hemoglobin concentration in the infant of only 2,1 g/dL. Neither mother nor child showed signs of metastatic disease. The macroscopic examination showed a hydropic placenta weighing more than 1 kilogram. Microscopy showed an intraplacental choriocarcinoma 3 cm in diameter. The tumor had infiltrated the maternal basal plate. Conclusion. Fetomaternal bleeding is a rare form of presentation of choriocarcinoma but its presence should always warrant detailed examination of placenta, mother, and infant. PMID:20204132

  18. Clinicopathological analysis of non-gestational ovarian choriocarcinoma: Report of two cases and review of the literature

    PubMed Central

    WANG, QIONG; GUO, CHAO; ZOU, LINGFENG; WANG, YUN; SONG, XIN; MA, YAQI; LIU, AIJUN

    2016-01-01

    The aim of the present study was to analyze the clinicopathological features of two cases of non-gestational ovarian choriocarcinoma (NGCO). The histopathological, immunohistochemical and clinical features of two cases of NGCO in the left ovaries of two 13 year-old female patients were investigated and the relevant literature was reviewed. In both cases, the tumor masses exhibited cribriform, papillary and nested cellular growth patterns, and hemorrhage and necrosis were evident. In case one, the patient also exhibited a sex cord tumor with annular tubules (SCTAT) in the right ovary. To the best of our knowledge, the synchronous occurrence of these two tumor types has not been reported previously. Immunohistochemically, the tumor cells of choriocarcinoma in both cases were positive for human chorionic gonadotropin and cytokeratin, while those of SCTAT were positive for CD56 and CD99. NGCO is an extremely rare germ cell tumor of high-grade malignancy, and STCAT is even rarer. Early metastasis of NGCO is common and the disease has a poor prognosis. In the present study, one patient succumbed within 4 months of diagnosis with NGCO and the other patient was lost to follow-up after 12 months. PMID:27073524

  19. Second trimester presentation of preeclampsia and choriocarcinoma in a primigravida with live birth.

    PubMed

    Luna Russo, Miguel A; Multani, Sukhpreet S; Ridgway, Mildred; Martin, James Nello

    2015-05-01

    Choriocarcinoma in the second trimester with a normal appearing live fetus is rare. A primigravida presented at 24 weeks' gestation with 5 days of worsening dyspnea and multiple widespread small lung nodules. Pelvic ultrasound revealed a normal intrauterine live singleton fetus with an extrauterine mass. Gestational hypertension progressed to preeclampsia with severe features and onset of vaginal bleeding. Cesarean delivery was undertaken with liveborn delivery and removal of an intrauterine mass confirmed to be choriocarcinoma. Postpartum treatment with multi-agent chemotherapy was initiated. The newborn thrived; the mother has no evidence of residual disease. PMID:24972034

  20. Genome-Wide High-Resolution aCGH Analysis of Gestational Choriocarcinomas

    PubMed Central

    Poaty, Henriette; Coullin, Philippe; Peko, Jean Félix; Dessen, Philippe; Diatta, Ange Lucien; Valent, Alexander; Leguern, Eric; Prévot, Sophie; Gombé-Mbalawa, Charles; Candelier, Jean-Jacques; Picard, Jean-Yves; Bernheim, Alain

    2012-01-01

    Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed. PMID:22253721

  1. Choriocarcinoma-associated pulmonary thromboembolism and pulmonary hypertension: a case report

    PubMed Central

    Zhu, Yan; Yu, Meining; Ma, Luyao; Xu, Hai; Li, Fanghong Rose

    2016-01-01

    Abstract Cases of pulmonary embolism and pulmonary artery hypertension caused by choriocarcinoma represent a rare clinical emergency. We report a case of a 25-year-old woman who presented with pulmonary embolism and hypertension and died soon after complete pulmonary embolectomy. A related literature review revealed that almost all of these patients had previously experienced a spontaneous abortion (average, 6 months) and were not pregnant. PMID:26423729

  2. Ectopic pregnancy with associated gestational choriocarcinoma in a California sea lion (Zalophus californianus).

    PubMed

    Fravel, Vanessa A; Lowenstine, Linda J; Koehne, Amanda

    2016-07-01

    A wild-born, captive-reared, 14 yr old, primiparous female California sea lion Zalophus californianus presented for anorexia of 14 d duration and abdominal distention. Routine complete blood cell count revealed leukocytosis with a neutrophilia, and serum chemistry revealed hypoalbumenemia and hyponatremia. Treatment with broad spectrum antibiotics and non-steroidal anti-inflammatories were started, but the animal continued to decline. Abdominal radiographs revealed a mature mineralized fetal skull and spine in the caudal abdomen and abdominal ultrasound revealed ascites but could not confirm the fetus. The patient was taken to surgery where a full term fetus was found outside of the uterus but within the fetal membranes, representing a secondary ectopic pregnancy. The patient passed away during surgery and was taken to necropsy. Gross necropsy revealed a diffuse peritonitis with yellow deposits over the serosal surfaces of the abdominal organs. The uterus appeared intact grossly and the ovaries appeared abnormal. The mesenteric, renal, and sub-lumbar nodes were enlarged and edematous. Histopathology revealed choriocarcinoma in the right uterine horn with evidence of chronic uterine rupture and protrusion of the placental tissue into the abdomen. The choriocarcinoma had metastasized locally as well as to the liver, spleen and lung. Choriocarcinoma is a highly malignant trophoblastic neoplasm that is rare in domestic animals. This case represents, to the authors' knowledge, the first report of gestational choriocarcinoma causing secondary ectopic pregnancy in a California sea lion and presents questions regarding pregnancy monitoring and management in a population of captive, minimally trained California sea lions. PMID:27409239

  3. Genotyping diagnosis of nongestational choriocarcinoma involving fallopian tube and broad ligament: a case study.

    PubMed

    Buza, Natalia; Rutherford, Thomas; Hui, Pei

    2014-01-01

    A 22 year-old G1P1 woman presented to the emergency room with clinical impression of "ruptured right adnexal mass" and underwent a right salpingo-oophorectomy to rule out ectopic pregnancy. Instead, gross and microscopic examination revealed a pure choriocarcinoma involving the right fallopian tube and broad ligament. On the basis of the patient's age, recent history of delivery, last menstrual period for 10 weeks, large tumor mass, and possible pelvic lymph node metastasis, the patient promptly started to receive 8 cycles of multiagent chemotherapy regimen with a working diagnosis of high-risk gestational choriocarcinoma. Subsequent DNA genotyping analysis showed that the tumor cells had an identical genetic profile to that of the normal tissue of the patient, therefore establishing a final diagnosis of nongestational choriocarcinoma. Six months after the initial presentation, a second surgery was performed to remove a persistent right para-adnexal mass, which showed only necrotic tissue upon microscopic examination. The patient received 1 additional cycle of multiagent chemotherapy. She was alive without evidence of recurrence 26 months after the initial diagnosis. PMID:24300537

  4. Choriocarcinoma of unknown origin with multiple organ metastasis and cerebral hemorrhage: A case report and literature review

    PubMed Central

    WEI, HONGTAO; ZHANG, TIANPENG; LIU, BING; XUE, XIAOWEI; WANG, GUOXING

    2016-01-01

    A 26-year-old man was admitted to Beijing Friendship Hospital, Capital Medical University (Beijing, China) with a 4-day history of headache, moderate fever and numbness in the right upper limb. Prior to this, the patient had been diagnosed with cerebral hemorrhage by computed tomography (CT) scan upon visiting a local hospital. Chest X-ray revealed multiple lesions in the lungs. Following referral, no abnormalities were found elsewhere, including in the testes, during a physical examination. Additional examination of other tumor biomarkers was unremarkable, and the initial suspicion of parasitic infection was ruled out. Tests revealed extremely high levels of β-human chorionic gonadotropin (>200,000 mIU/ml). In addition, CT scans showed multiple metastases in the head, lungs, liver and kidneys. An ultrasound-guided Tru-Cut biopsy of the liver was performed in order to form a definitive diagnosis. Although the patient was treated with mannitol to reduce intracranial pressure, and with cefoperazone sodium and sulbactam sodium to fight infection, the patient succumbed to a cerebral hernia on the fourth day of hospitalization. Following this, the ultrasound-guided Tru-Cut liver biopsy result was received, which suggested a diagnosis of choriocarcinoma. PMID:27313687

  5. Influence of different growth factors on a rat choriocarcinoma cell line.

    PubMed

    Verstuyf, A; Goebels, J; Sobis, H; Vandeputte, M

    1993-01-01

    The influence of epidermal growth factor, insulin-like growth factors I and II, insulin, transforming growth factor beta 1 and transferrin on the growth of a postgestational rat choriocarcinoma was examined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The cell line was cultured in RPMI 1640 medium supplemented with fetal calf serum, beta-mercaptoethanol, glucose, sodium pyruvate and antibiotics. The experiments were done in media supplemented with 10% (optimal) or 3% (suboptimal) fetal calf serum. Among the different growth factors tested, only epidermal growth factor and to a certain extent insulin had a growth-promoting effect by themselves. The other growth factors had either an additive effect in the presence of epidermal growth factor or no effect at all. The cytotrophoblast cells expressed both epidermal growth factor and transferrin receptors whereas the more differentiated giant cells expressed only transferrin receptors. PMID:8493450

  6. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage.

    PubMed

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551-554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations. PMID:27403124

  7. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

    PubMed Central

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.

  8. Methylation status and transcriptional expression of the MHC class I loci in human trophoblast cells from term placenta

    SciTech Connect

    Guillaudeux, T.; Rodriguez, A.M.; Girr, M.

    1995-04-01

    Of the various molecular regulatory mechanisms that may be used by human trophoblast cells to down-regulate expression of HLA class I genes, we chose to investigate the methylation of DNA, generally associated with inhibition of transcription. We analyzed the methylation status of different HLA class I loci in villous and extravillous cytotrophoblast cells and in vitro-differentiated syncytiotrophoblast, purified from human term placenta, as well as in the human trophoblast-derived JAR and JEG-3 cell lines. We then compared methylation status and transcriptional activity. An inverse relationship was established between JAR and JEG-3: HLA-A, -B, and -G are methylated and repressed in JAR, whereas in JEG-3, HLA-A is methylated and repressed but HLA-B and -G are partially methylated and transcribed. HLA-E is unmethylated and transcribed in both cell lines. Apart from HLA-E, which is always unmethylated and transcribed, no such relationship exists for the other class I loci in trophoblast cells. Whereas nonclassical HLA-G and classical HLA-A and -B class I genes are undermethylated in both cytotrophoblast and syncytiotrophoblast, they are clearly transcribed in the former but minimally transcribed in the latter subpopulation. Thus, the down-regulation of class I gene expression in the in vitro-differentiated synctiotrophoblast is unlikely to be caused by DNA methylation. Furthermore, there is no detectable expression of any class I molecule at the cell surface of either trophoblast cell subpopulation, suggesting a negative control on translation and/or on the secretory pathway to the plasma membrane. 50 refs., 11 figs., 1 tab.

  9. Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves

    PubMed Central

    Hochstrasser, Tanja; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell damage was nearly negated by reducing cavitation. Furthermore, cell viability decreased progressively with higher numbers of rESWs. Exposure to rESWs had no impact on growth potential of JEG-3 cells, but dose-dependently increased growth potential of HFFF2 cells. Cultivation of cells that were initially exposed to sham-rESWs in conditioned media increased the growth potential of HFFF2 cells, nevertheless, an even stronger effect was achieved by direct exposure to rESWs. Additionally, cell cycle distribution analysis demonstrated a shift in proportion from G0/G1 to G2/M phase in HFFF2 cells, but not in JEG-3 cells. These data demonstrate that rESWs leads to initial and subsequent dose-dependent and cell type-specific effects in vitro. PMID:27477873

  10. Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves.

    PubMed

    Hochstrasser, Tanja; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell damage was nearly negated by reducing cavitation. Furthermore, cell viability decreased progressively with higher numbers of rESWs. Exposure to rESWs had no impact on growth potential of JEG-3 cells, but dose-dependently increased growth potential of HFFF2 cells. Cultivation of cells that were initially exposed to sham-rESWs in conditioned media increased the growth potential of HFFF2 cells, nevertheless, an even stronger effect was achieved by direct exposure to rESWs. Additionally, cell cycle distribution analysis demonstrated a shift in proportion from G0/G1 to G2/M phase in HFFF2 cells, but not in JEG-3 cells. These data demonstrate that rESWs leads to initial and subsequent dose-dependent and cell type-specific effects in vitro. PMID:27477873

  11. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis.

    PubMed

    Blazquez, Alba G; Briz, Oscar; Gonzalez-Sanchez, Ester; Perez, Maria J; Ghanem, Carolina I; Marin, Jose J G

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. PMID:24631341

  12. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    SciTech Connect

    Blazquez, Alba G.; Briz, Oscar; Gonzalez-Sanchez, Ester; Perez, Maria J.; Ghanem, Carolina I.; Marin, Jose J.G.

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  13. Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter.

    PubMed

    Castiglioni, V; Farhang Ghahremani, M; Goossens, S; De Maglie, M; Ardizzone, M; Haigh, J J; Radaelli, E

    2015-07-01

    Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors' knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors. PMID:25253064

  14. Long-chain polyunsaturated fatty acids stimulate cellular fatty acid uptake in human placental choriocarcinoma (BeWo) cells.

    PubMed

    Johnsen, G M; Weedon-Fekjaer, M S; Tobin, K A R; Staff, A C; Duttaroy, A K

    2009-12-01

    Supplementation of long-chain polyunsaturated fatty acids (LCPUFAs) is advocated during pregnancy in some countries although very little information is available on their effects on placental ability to take up these fatty acids for fetal supply to which the fetal growth and development are critically dependent. To identify the roles of LCPUFAs on placental fatty acid transport function, we examined the effects of LCPUFAs on the uptake of fatty acids and expression of fatty acid transport/metabolic genes using placental trophoblast cells (BeWo). Following 24 h incubation of these cells with 100 microM of LCPUFAs (arachidonic acid, 20:4n-6, eicosapentaenoic acid, 20:5n-3, or docosahexaenoic acid, 22:6n-3), the cellular uptake of [(14)C] fatty acids was increased by 20-50%, and accumulated fatty acids were preferentially incorporated into phospholipid fractions. Oleic acid (OA, 18:1n-9), on the other hand, could not stimulate fatty acid uptake. LCPUFAs and OA increased the gene expression of ADRP whilst decreased the expression of ASCL3, ACSL4, ACSL6, LPIN1, and FABP3 in these cells. However, LCPUFAs but not OA increased expression of ACSL1 and ACSL5. Since acyl-CoA synthetases are involved in cellular uptake of fatty acids via activation for their channelling to lipid metabolism and/or for storage, the increased expression of ACSL1 and ACLS5 by LCPUFAs may be responsible for the increased fatty acid uptake. These findings demonstrate that LCPUFA may function as an important regulator of general fatty acid uptake in trophoblast cells and may thus have impact on fetal growth and development. PMID:19880178

  15. Calcium-dependent trichosanthin-induced generation of reactive oxygen species involved in apoptosis of human choriocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, Chunyang; Ma, Hui; Chen, Die Yan

    2001-04-01

    The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumor and anti-HIV. We found for the first time that TCS induced production of reactive oxygen species (ROS) in JAR cells by using fluorescent probe 2',7'-dichlorofluorescin diacetate with confocal laser scanning microscopy. TCS-induced ROS showed dependence on the increase in intracellular calcium and on the presence of extracellular calcium. The production of ROS increased rapidly after the application of TCS, which paralleled TCS-indued increase in intracellular calcium monitored using fluo 3-AM, suggesting that TCS-induced ROS might mediate by the increase in intracellular Ca2PLU concentration. Simultaneous observation of the nuclear morphological changes and production of ROS in JAR cells with two-photon laser scanning microscopy and confocal laser scanning microscopy revealed that ROS involved in the apoptosis of JAR cells, which was confirmed by that antioxidant (alpha) -tocopherol prevented TCS-induced ROS formation and cell death. The finding that calcium-dependent TCS-induced ROS involved in the apoptosis of JAR cells might provide new insight into the anti-tumor and anti-HIV mechanism of TCS.

  16. Expression and localization of StarD7 in trophoblast cells.

    PubMed

    Angeletti, S; Rena, V; Nores, R; Fretes, R; Panzetta-Dutari, G M; Genti-Raimondi, S

    2008-05-01

    The StAR-related lipid transfer (START) domain is defined as a motif of around 200 amino acids implicated in lipid/sterol binding. In a previous study, we identified the StarD7 transcript encoding one of the 15 family members with START domain present in the human genome. This transcript was found to be overexpressed in choriocarcinoma JEG-3 cells. In addition, we demonstrated that the recombinant StarD7 protein forms stable Gibbs and Langmuir monolayers at the air-buffer interface, showing marked surface activity and interaction with phospholipid monolayers, mainly with phosphatidylserine, cholesterol and phosphatidylglycerol. This study was undertaken to evaluate the expression and localization of StarD7 protein in trophoblastic samples. Here, we show for the first time the presence of StarD7 protein in human trophoblast cells. Western blot assays revealed a unique specific 34 kDa protein in JEG-3 cell line, choriocarcinoma tissue, complete hydatidiform mole, early and normal term placenta. Immunohistochemical data from early and normal term placentas and complete hydatidiform moles showed that this protein is abundant in the syncytiotrophoblasts, mainly at the apical side of the syncytium, with a weak and focal reaction in the cytotrophoblast cells. Furthermore, an increased StarD7 mRNA and protein expression, as well as a change in its sub-cellular localization was observed in in vitro differentiating cytotrophoblast isolated from normal term placenta. Taken together, these findings support and allow future studies to explore the possibility that StarD7 protein mediates transplacental lipid transport and/or is involved in syncytialization. PMID:18378304

  17. Trophoblast origin of hCG isoforms: cytotrophoblasts are the primary source of choriocarcinoma-like hCG.

    PubMed

    Kovalevskaya, G; Genbacev, O; Fisher, S J; Caceres, E; O'Connor, J F

    2002-08-30

    We have previously demonstrated that a hyperglycosylated isoform of chorionic gonadotropin (hCG) (B152 hCG) is detected in the blood and urine in early pregnancy and is subsequently rapidly replaced by the hCG isoform (B109 hCG) characteristic of later pregnancy. In the current study we have extended our work on the origin of these isoforms. We have used a combination of in situ and in vitro approaches. Localization studies in placental tissues showed that monoclonal antibody B109 stained very specifically syncytiotrophoblast (STBs) from first and second trimester tissues. At term, STBs exhibited no B109 staining at all. Immunostaining with B152 antibody, that recognize the hyperglycosylated isoform of hCG, revealed only punctate staining of STBs in most villi of first trimester tissue. Both antibodies B109 and B152 failed to stain cytotrophoblasts (CTBs). To assess the functional relevance of these observations we analyzed conditioned media from purified CTBs using two immunometric assays, one of which (B152-B207*) has primary specificity for the hyperglycosylated, choriocarcinoma-like hCG and the other (B109-B108*) having primary specificity for the later pregnancy hCG isoform. Regardless of gestational age, isolated CTBs secreted predominantly B152 hCG isoform in contrast to placental villi (predominantly STBs), which released primarily the B109 hCG isoform. Isolated CTBs, however, failed to immunostain with both B109 and B152 antibodies. To resolve this contradiction, we cultured CTBs in the presence of brefeldin A, a drug known to block secretion by inhibiting protein translocation from the endoplasmic reticulum to the Golgi vesicles. Brefeldin A treated CTBs stained strongly with B109 and did not stain or stained weakly with B152 antibody. We assume that treatment with brefeldin A impaired glycosylation of beta subunit and consequently inhibited the production of hyperglycosylated form of hCG recognized by B152. In summary, our in vitro experiments indicate

  18. MicroRNA-212 Regulates the Expression of Olfactomedin 1 and C-Terminal Binding Protein 1 in Human Endometrial Epithelial Cells to Enhance Spheroid Attachment In Vitro.

    PubMed

    Kottawatta, Kottawattage S A; So, Kam-Hei; Kodithuwakku, Suranga P; Ng, Ernest H Y; Yeung, William S B; Lee, Kai-Fai

    2015-11-01

    Successful embryo implantation requires a synchronized dialogue between a competent blastocyst and the receptive endometrium, which occurs in a limited time period known as the "window of implantation." Recent studies suggested that down-regulation of olfactomedin 1 (OLFM1) in the endometrium and fallopian tube is associated with receptive endometrium and tubal ectopic pregnancy in humans. Interestingly, the human chorionic gonadotropin (hCG) induces miR-212 expression, which modulates OLFM1 and C-terminal binding protein 1 (CTBP1) expressions in mouse granulosa cells. Therefore, we hypothesized that embryo-derived hCG would increase miR-212 expression and down-regulate OLFM1 and CTBP1 expressions to favor embryo attachment onto the female reproductive tract. We found that hCG stimulated the expression of miR-212 and down-regulated OLFM1 but not CTBP1 mRNA in both human endometrial (Ishikawa) and fallopian (OE-E6/E7) epithelial cells. However, hCG suppressed the expression of OLFM1 and CTBP1 proteins in both cell lines. The 3'UTR of both OLFM1 and CTBP1 contained binding sites for miR-212. The miR-212 precursor suppressed luciferase expression, whereas the miR-212 inhibitor stimulated luciferase expression of the wild-type (WT)-OLFM1 and WT-CTBP1 reporter constructs. Furthermore, hCG (25 IU/ml) treatments stimulated trophoblastic (Jeg-3) spheroid (blastocyst surrogate) attachment onto Ishikawa and OE-E6/E7 cells. Transfection of miR-212 precursor increased Jeg-3 spheroid attachment onto Ishikawa cells and decreased OLFM1 and CTBP1 protein expressions, whereas the opposite occurred with miR-212 inhibitor. Taken together, hCG stimulated miR-212, which in turn down-regulated OLFM1 and CTBP1 expression in fallopian and endometrial epithelial cells to favor spheroid attachment. PMID:26377223

  19. Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein.

    PubMed Central

    Mitchell, E J; Lee, K; O'Connor-McCourt, M D

    1992-01-01

    Transforming growth factor-beta (TGF-beta) is a potential mediator of placental trophoblast functions, including differentiation, hormone production, endometrial invasion, and immunosuppression. Equilibrium binding and affinity-labeling assays were used to investigate the binding characteristics of TGF-beta 1 and TGF-beta 2 on an established human choriocarcinoma trophoblastic cell line (BeWo). The equilibrium binding experiments indicated that the BeWo cells exhibited similar average affinities and total number of binding sites for TGF-beta 1 and TGF-beta 2. The Kd values obtained from Scatchard analyses were approximately 65 pM for 125I-TGF-beta 1 and approximately 40 pM for 125I-TGF-beta 2, with 70,000 and 85,000 sites per cell, respectively. Competitive equilibrium binding experiments indicated that TGF-beta 1 and TGF-beta 2 were equipotent (apparent half maximal inhibition [IC50] approximately 70 pM) and that all binding sites were capable of recognizing both isoforms. Affinity-labeling studies with 125I-TGF-beta 1 and 125I-TGF-beta 2 and the chemical cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) revealed a predominant type III/betaglycan receptor, a low level of apparently heterogeneous type I and II receptors and an additional novel 38-kDa TGF-beta binding glycoprotein that was present both under reducing and nonreducing conditions on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Affinity-labeling saturation and competition studies indicated that the type III/betaglycan component appears to have a 7-fold higher capacity for TGF-beta 1 than for -beta 2 yet exhibits a 5- to 10-fold higher affinity for TGF-beta 2 than for -beta 1. The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor. This 38-kDa binding protein appears to be upregulated after methotrexate-induced differentiation of the

  20. Human NR5A1/SF-1 Mutations Show Decreased Activity on BDNF (Brain-Derived Neurotrophic Factor), an Important Regulator of Energy Balance: Testing Impact of Novel SF-1 Mutations Beyond Steroidogenesis

    PubMed Central

    Malikova, Jana; Camats, Núria; Fernández-Cancio, Mónica; Heath, Karen; González, Isabel; Caimarí, María; del Campo, Miguel; Albisu, Marian; Kolouskova, Stanislava; Audí, Laura; Flück, Christa E.

    2014-01-01

    Context Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. Objective To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. Patients 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. Methods SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). Results Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. Conclusions Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations. PMID:25122490

  1. Gossypol enantiomers potently inhibit human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase activities.

    PubMed

    Dong, Yaoyao; Mao, Baiping; Li, Linxi; Guan, Hongguo; Su, Ying; Li, Xiaoheng; Lian, Qingquan; Huang, Ping; Ge, Ren-Shan

    2016-03-01

    Gossypol is a chemical isolated from cotton seeds. It exists as (+) or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+)- and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 μM, while (-) gossypol weakly inhibited it with IC50 over 100 μM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 μM, while (+) gossypol had no inhibition when the highest concentration (100 μM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects. PMID:26709042

  2. Leptin promotes cell proliferation and survival of trophoblastic cells.

    PubMed

    Magariños, María Paula; Sánchez-Margalet, Víctor; Kotler, Mónica; Calvo, Juan Carlos; Varone, Cecilia L

    2007-02-01

    Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by (3)H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 microM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 microM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. PMID:17021346

  3. Role of the Cyclic AMP Response Element Binding Complex and Activation of Mitogen-Activated Protein Kinases in Synergistic Activation of the Glycoprotein Hormone α Subunit Gene by Epidermal Growth Factor and Forskolin

    PubMed Central

    Roberson, Mark S.; Ban, Makiko; Zhang, Tong; Mulvaney, Jennifer M.

    2000-01-01

    The aim of these studies was to elucidate a role for epidermal growth factor (EGF) signaling in the transcriptional regulation of the glycoprotein hormone α subunit gene, a subunit of chorionic gonadotropin. Studies examined the effects of EGF and the adenylate cyclase activator forskolin on the expression of a transfected α subunit reporter gene in a human choriocarcinoma cell line (JEG3). At maximal doses, administration of EGF resulted in a 50% increase in a subunit reporter activity; forskolin administration induced a fivefold activation; the combined actions of EGF and forskolin resulted in synergistic activation (greater than eightfold) of the α subunit reporter. Mutagenesis studies revealed that the cyclic AMP response elements (CRE) were required and sufficient to mediate EGF-forskolin-induced synergistic activation. The combined actions of EGF and forskolin resulted in potentiated activation of extracellular signal-regulated kinase (ERK) enzyme activity compared with EGF alone. Specific blockade of ERK activation was sufficient to block EGF-forskolin-induced synergistic activation of the α subunit reporter. Pretreatment of JEG3 cells with a p38 mitogen-activated protein kinase inhibitor did not influence activation of the α reporter. However, overexpression of c-Jun N-terminal kinase (JNK)-interacting protein 1 as a dominant interfering molecule abolished the synergistic effects of EGF and forskolin on the α subunit reporter. CRE binding studies suggested that the CRE complex consisted of CRE binding protein and EGF-ERK-dependent recruitment of c-Jun–c-Fos (AP-1) to the CRE. A dominant negative form of c-Fos (A-Fos) that specifically disrupts c-Jun–c-Fos DNA binding inhibited synergistic activation of the α subunit. Thus, synergistic activation of the α subunit gene induced by EGF-forskolin requires the ERK and JNK cascades and the recruitment of AP-1 to the CRE binding complex. PMID:10779323

  4. A monoclonal antibody against leptin.

    PubMed

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  5. Differential effects of glyphosate and roundup on human placental cells and aromatase.

    PubMed

    Richard, Sophie; Moslemi, Safa; Sipahutar, Herbert; Benachour, Nora; Seralini, Gilles-Eric

    2005-06-01

    Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation. PMID:15929894

  6. Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase

    PubMed Central

    Richard, Sophie; Moslemi, Safa; Sipahutar, Herbert; Benachour, Nora; Seralini, Gilles-Eric

    2005-01-01

    Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation. PMID:15929894

  7. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    PubMed Central

    Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

  8. Regulated expression of ADAMTS-12 in human trophoblastic cells: a role for ADAMTS-12 in epithelial cell invasion?

    PubMed

    Beristain, Alexander G; Zhu, Hua; Leung, Peter C K

    2011-01-01

    Metastatic carcinoma cells exploit the same molecular machinery that allows human placental cytotrophoblasts to develop an invasive phenotype. As altered expression levels of ADAMTS (ADisintegrin And Metalloproteinase with ThromboSpondin repeats) subtypes have been associated with cancer progression, we have examined the function and regulation of members of this gene family in epithelial cell invasion using cultures of highly invasive extravillous cytotrophoblasts and the poorly invasive JEG-3 cytotrophoblast cell line as model systems. Of the multiple ADAMTS subtypes identified in first trimester human placenta and these two trophoblastic cell types, only ADAMTS-12 was preferentially expressed by extravillous cytotrophoblasts. Transforming growth factor-β1 and interleukin-1β, two cytokines that promote and restrain cytotrophoblast invasion in vitro, were also found to differentially regulate trophoblastic ADAMTS-12 mRNA levels. Loss- or gain-of-function studies confirmed that ADAMTS-12, independent of its proteolytic activity, plays a specific, non-redundant role in trophoblast invasion. Furthermore, we demonstrated that ADAMTS-12 regulated cell-extracellular matrix adhesion and invasion through a mechanism involving the αvβ3 integrin heterodimer. This study identifies a novel biological role for ADAMTS-12, and highlights the importance and complexity of its non-proteolytic domain(s) pertaining to its function. PMID:21494557

  9. Regulated Expression of ADAMTS-12 in Human Trophoblastic Cells: A Role for ADAMTS-12 in Epithelial Cell Invasion?

    PubMed Central

    Beristain, Alexander G.; Zhu, Hua; Leung, Peter C. K.

    2011-01-01

    Metastatic carcinoma cells exploit the same molecular machinery that allows human placental cytotrophoblasts to develop an invasive phenotype. As altered expression levels of ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin repeats) subtypes have been associated with cancer progression, we have examined the function and regulation of members of this gene family in epithelial cell invasion using cultures of highly invasive extravillous cytotrophoblasts and the poorly invasive JEG-3 cytotrophoblast cell line as model systems. Of the multiple ADAMTS subtypes identified in first trimester human placenta and these two trophoblastic cell types, only ADAMTS-12 was preferentially expressed by extravillous cytotrophoblasts. Transforming growth factor-β1 and interleukin-1β, two cytokines that promote and restrain cytotrophoblast invasion in vitro, were also found to differentially regulate trophoblastic ADAMTS-12 mRNA levels. Loss- or gain-of-function studies confirmed that ADAMTS-12, independent of its proteolytic activity, plays a specific, non-redundant role in trophoblast invasion. Furthermore, we demonstrated that ADAMTS-12 regulated cell-extracellular matrix adhesion and invasion through a mechanism involving the αvβ3 integrin heterodimer. This study identifies a novel biological role for ADAMTS-12, and highlights the importance and complexity of its non-proteolytic domain(s) pertaining to its function. PMID:21494557

  10. MSX2 Induces Trophoblast Invasion in Human Placenta.

    PubMed

    Liang, Hao; Zhang, Qian; Lu, Junjie; Yang, Genling; Tian, Na; Wang, Xiaojie; Tan, Yi; Tan, Dongmei

    2016-01-01

    Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated

  11. MSX2 Induces Trophoblast Invasion in Human Placenta

    PubMed Central

    Lu, Junjie; Yang, Genling; Tian, Na; Wang, Xiaojie; Tan, Yi; Tan, Dongmei

    2016-01-01

    Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated

  12. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    PubMed Central

    2013-01-01

    Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

  13. Expression of Placental Members of the Human Growth Hormone Gene Family Is Increased in Response to Sequential Inhibition of DNA Methylation and Histone Deacetylation

    PubMed Central

    Ganguly, Esha; Bock, Margaret E.; Cattini, Peter A.

    2015-01-01

    Abstract The genes coding for human (h) chorionic somatomammotropin (CS), hCS-A and hCS-B, and placental growth hormone (GH-V), hGH-V, are located at a single locus on chromosome 17. Efficient expression of these placental genes has been linked to local regulatory (5′ P and 3′ enhancer) sequences and a remote locus control region (LCR), in part, through gene transfer in placental and nonplacental tumor cells. However, low levels of endogenous hCS/GH-V transcripts are reported in the same cells compared with term placenta, suggesting that chromatin structure, or regulatory region accessibility, versus transcription factor availability contributes to the relatively low levels. To assess individual hCS-A, CS-B, and GH-V gene expression in placental and nonplacental tumor cells and the effect of increasing chromatin accessibility by inhibiting DNA methylation and histone deacetylation using 5-aza-2′-deoxycytidine (azadC) and trichostatin A (TSA). Low levels of hCS-A, CS-B, and GH-V were detected in placental and nonplacental tumor cells compared with term placenta. A significant >5-fold increase in activity was seen in placental, but not nonplacental, cells transfected with hybrid hCS promoter luciferase genes containing 3′ enhancer sequences. Pretreatment of placental JEG-3 cells with azadC resulted in a >10-fold increase in hCS-A, CS-B, and GH-V RNA levels with TSA treatment compared with TSA treatment alone. This effect was specific as reversing the treatment regimen did not have the same effect. An assessment of hyperacetylated H3/H4 in JEG-3 cells treated with azadC and TSA versus TSA alone revealed significant increases consistent with a more open chromatin structure, including the hCS 3′ enhancer sequences and LCR. These observations suggest that accessibility of remote and local regulatory regions required for efficient placental hGH/CS expression can be restricted by DNA methylation and histone acetylation status. This includes restricting access of

  14. Tumor cell-endothelial cell interactions: evidence for roles for lipoxygenase products of arachidonic acid in metastasis.

    PubMed

    Damtew, B; Spagnuolo, P J

    1997-04-01

    Adhesion of tumor cells (TC) to endothelial cells (EC) is necessary for movement of TC out of the interstitium to form metastatic deposits. This interaction may be influenced by proadhesive molecules such as lipoxygenase products of arachidonic acid metabolism. We studied the effect of inflammatory stimuli, A23187 calcium ionophore, n-formyl-methionyl-leucine-phenylalanine (FMLP) and phorbol myristate acetate (PMA) on TC-EC interaction. Adherence of metastatic breast tumor cell line (MCF-7), choriocarcinoma cell line (JEG-3), and non metastatic pituitary cell (GH-3) were assayed as the number of radiolabeled TC attached to EC (cpm/well). TC and EC were incubated with A23187, FMLP, and PMA for varying time periods. Lipoxygenase products (LTB4, 5-HETE) were measured under basal and stimulated conditions using RP-HPLC and RIA. There were no differences in basal adherence of TC lines to EC. When EC were incubated with stimuli, there were significant increases in the numbers of MCF-7 and JEG-3 cells adherent to EC compared to GH-3. Light and phase contrast microscopy confirmed that TC were attached to EC. Upon stimulation, GH-3 preferentially produced prostaglandins (PGI1(2)) while MCF-7 and JEG-3 produced lipoxygenase products (LTB4 and 5-HETE). Pre-incubation of MCF-7 and JEG-3 with the lipoxygenase inhibitor nordihydroguiaretic acid resulted in partial inhibition of adhesion to EC. Our data strongly indicate a role for lipoxygenase products of arachidonic acid in adherence of TC to EC. PMID:9150375

  15. Basal expression of the cystic fibrosis transmembrane conductance regulator gene is dependent on protein kinase A activity.

    PubMed Central

    McDonald, R A; Matthews, R P; Idzerda, R L; McKnight, G S

    1995-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel that becomes activated after phosphorylation by cAMP-dependent protein kinase (PKA). We demonstrate that PKA also plays a crucial role in maintaining basal expression of the CFTR gene in the human colon carcinoma cell line T84. Inhibition of PKA activity by expression of a dominant-negative regulatory subunit or treatment with the PKA-selective inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89) caused a complete suppression of CFTR gene expression without affecting other constitutively active genes. Basal expression of a 2.2-kb region of the CFTR promoter linked to a luciferase reporter gene (CFTR-luc) exhibited the same dependence on PKA. The ability of cAMP to induce CFTR over basal levels is cell-type specific. In T84 cells, both the endogenous CFTR gene and CFTR-luc exhibited only a modest inducibility (approximately 2-fold), whereas in the human choriocarcinoma cell line JEG-3, CFTR-luc could be induced at least 4-fold. A variant cAMP-response element is present at position -48 to -41 in the CFTR promoter, and mutation of this sequence blocks basal expression. We conclude that cAMP, acting through PKA, is an essential regulator of basal CFTR gene expression and may mediate an induction of CFTR in responsive cell types. Images Fig. 1 Fig. 3 PMID:7543684

  16. Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro.

    PubMed

    Zou, Yanfen; Yu, Xiang; Lu, Jing; Jiang, Ziyan; Zuo, Qing; Fan, Mingsong; Huang, Shiyun; Sun, Lizhou

    2015-01-01

    Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells' metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia. PMID:26357650

  17. Modulation of AP-1 activity by the human progesterone receptor in endometrial adenocarcinoma cells.

    PubMed Central

    Bamberger, A M; Bamberger, C M; Gellersen, B; Schulte, H M

    1996-01-01

    The composite transcription factor activating protein 1 (AP-1) integrates various mitogenic signals in a large number of cell types, and is therefore a major regulator of cell proliferation. In the normal human endometrium, proliferation and differentiation alternate in a cyclic fashion, with progesterone being largely implicated in the latter process. However, the effects of progesterone and the progesterone receptor (hPR) on AP-1 activity in the human endometrium are not known. To address this issue, HEC-1-B endometrial adenocarcinoma cells, which are devoid of hPR, were transfected with luciferase reporter constructs driven by two different AP-1-dependent promoters. Unexpectedly, cotransfection of hPR caused a marked induction of luciferase activity in the absence of ligand on both promoters. The magnitude of this induction was similar to that observed in response to the phorbol ester TPA. Addition of ligand reversed the stimulating effect of the unliganded hPR on AM activity in these cells. These effects were specific for hPR, and were not observed with either human estrogen receptor or human glucocorticoid receptor. Furthermore, they strictly depended on the presence of AP-1-responsive sequences within target promoters. Finally, the described effects of hPR on AP-1 activity were shown to be cell-type specific, because they could not be demonstrated in SKUT-1-B, JEG-3, and COS-7 cells. To our knowledge this is the first report of an unliganded steroid receptor stimulating AP-1 activity. This effect and its reversal in the presence of ligand suggest a novel mechanism, through which hPR can act as a key regulator of both proliferation and differentiation in the human endometrium. PMID:8650238

  18. Human endogenous retrovirus envelope proteins target dendritic cells to suppress T-cell activation.

    PubMed

    Hummel, Jonas; Kämmerer, Ulrike; Müller, Nora; Avota, Elita; Schneider-Schaulies, Sibylle

    2015-06-01

    Though mostly defective, human endogenous retroviruses (HERV) can retain open reading frames, which are especially expressed in the placenta. There, the envelope (env) proteins of HERV-W (Syncytin-1), HERV-FRD (Syncytin-2), and HERV-K (HML-2) were implicated in tolerance against the semi-allogenic fetus. Here, we show that the known HERV env-binding receptors ASCT-1 and -2 and MFSD2 are expressed by DCs and T-cells. When used as effectors in coculture systems, CHO cells transfected to express Syncytin-1, -2, or HML-2 did not affect T-cell expansion or overall LPS-driven phenotypic DC maturation, however, promoted release of IL-12 and TNF-α rather than IL-10. In contrast, HERV env expressing choriocarcinoma cell lines suppressed T-cell proliferation and LPS-induced TNF-α and IL-12 release, however, promoted IL-10 accumulation, indicating that these effects might not rely on HERV env interactions. However, DCs conditioned by choriocarcinoma, but also transgenic CHO cells failed to promote allogenic T-cell expansion. This was associated with a loss of DC/T-cell conjugate frequencies, impaired Ca(2+) mobilization, and aberrant patterning of f-actin and tyrosine phosphorylated proteins in T-cells. Altogether, these findings suggest that HERV env proteins target T-cell activation indirectly by modulating the stimulatory activity of DCs. PMID:25752285

  19. Molecular analysis of the human SLC13A4 sulfate transporter gene promoter

    SciTech Connect

    Jefferis, J.; Rakoczy, J.; Simmons, D.G.; Dawson, P.A.

    2013-03-29

    Highlights: ► Basal promoter activity of SLC13A4 −57 to −192 nt upstream of transcription initiation site. ► Human SLC13A4 5′-flanking region has conserved motifs with other placental species. ► Putative NFY, SP1 and KLF7 motifs in SLC13A4 5′-flanking region enhance transcription. -- Abstract: The human solute linked carrier (SLC) 13A4 gene is primarily expressed in the placenta where it is proposed to mediate the transport of nutrient sulfate from mother to fetus. The molecular mechanisms involved in the regulation of SLC13A4 expression remain unknown. To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the human SLC13A4 5′-flanking region in the JEG-3 placental cell line using luciferase reporter assays. Basal transcriptional activity was identified in the region −57 to −192 nucleotides upstream of the SLC13A4 transcription initiation site. Mutational analysis of the minimal promoter region identified Nuclear factor Y (NFY), Specificity protein 1 (SP1) and Krüppel like factor 7 (KLF7) motifs which conferred positive transcriptional activity, as well as Zinc finger protein of the cerebellum 2 (ZIC2) and helix–loop–helix protein 1 (HEN1) motifs that repressed transcription. The conserved NFY, SP1, KLF7, ZIC2 and HEN1 motifs in the SLC13A4 promoter of placental species but not in non-placental species, suggests a potential role for these putative transcriptional factor binding motifs in the physiological control of SLC13A4 mRNA expression.

  20. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.

    PubMed

    Mesnage, R; Bernay, B; Séralini, G-E

    2013-11-16

    Pesticides are always used in formulations as mixtures of an active principle with adjuvants. Glyphosate, the active ingredient of the major pesticide in the world, is an herbicide supposed to be specific on plant metabolism. Its adjuvants are generally considered as inert diluents. Since side effects for all these compounds have been claimed, we studied potential active principles for toxicity on human cells for 9 glyphosate-based formulations. For this we detailed their compositions and toxicities, and as controls we used a major adjuvant (the polyethoxylated tallowamine POE-15), glyphosate alone, and a total formulation without glyphosate. This was performed after 24h exposures on hepatic (HepG2), embryonic (HEK293) and placental (JEG3) cell lines. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. The compositions in adjuvants were analyzed by mass spectrometry. Here we demonstrate that all formulations are more toxic than glyphosate, and we separated experimentally three groups of formulations differentially toxic according to their concentrations in ethoxylated adjuvants. Among them, POE-15 clearly appears to be the most toxic principle against human cells, even if others are not excluded. It begins to be active with negative dose-dependent effects on cellular respiration and membrane integrity between 1 and 3ppm, at environmental/occupational doses. We demonstrate in addition that POE-15 induces necrosis when its first micellization process occurs, by contrast to glyphosate which is known to promote endocrine disrupting effects after entering cells. Altogether, these results challenge the establishment of guidance values such as the acceptable daily intake of glyphosate, when these are mostly based on a long term in vivo test of glyphosate alone. Since pesticides are always used with adjuvants that could change their toxicity, the necessity to assess their whole formulations as mixtures becomes obvious. This challenges

  1. Expression of human LINE-1 elements in enhanced by isochromosome 12p; evidence from testicular germ cell tumors and the Pallister-Killian syndrome

    SciTech Connect

    Swergold, D.

    1994-09-01

    Expression of the human LINE-1 (L1Hs) transposable element is restricted to a narrow range of cell types. Specific expression of either endogenous elements or transfected recombinant elements has been reported primarily in tumors and cell lines of germ cell origin, including the NTera2D1, 2102EP, and JEG3 cell lines. These tumors and cell lines often contain one or more copies of isochromosome 12p, or translocations of 12p. Another human condition, the Pallister-Killian syndrome, is also characterized by the mosaic presence of an isochromosome 12p in patient`s cells. M28, a previously described somatic hybrid cell line, contains a human isochromosone 12p derived from fibroblasts of a patient with Pallister-Killian syndrome in a mouse LMTK-background. I asked whether the M28 cell line would exhibit enhanced expression of endogenous or transfected L1Hs elements. Expression of transfected recombinant L1Hs elements was 10-20 fold higher in M28 than in LMTK-cells. Expression of L1Hs elements was not increased in the GM10868A somatic cell hybrid line which contains a complete human chromosome 12 in a Chinese Hamster Ovary background. Somatic cell hybrid lines containing various human chromosomes in a LMTK-background also exhibited no enhanced L1Hs expression. P40, the protein encoded by the L1Hs first open reading frame, was detected in NTera2D1 but not in non-transfected M28 cells. Preliminary promoter deletion experiments indicate that similar, but non-identical regions of the L1Hs 5{prime} UTR, contribute to high level expression in the NTera2D1 and the M28 cell lines. These data suggest that the enhanced expression of human LINE-1 elements in tumors of germ cell origin is due in part to the presence of the isochromosome 12p.

  2. Toxicity of diuron in human cancer cells.

    PubMed

    Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

    2015-10-01

    Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. PMID:26086120

  3. Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs.

    PubMed

    Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; Tsang, Jessica Oi-Ling; Tee, Kah-Meng; Cai, Jian-Piao; Chik, Kenn Ka-Heng; Zhu, Zheng; Chan, Chris Chung-Sing; Choi, Garnet Kwan-Yue; Sridhar, Siddharth; Zhang, Anna Jinxia; Lu, Gang; Chiu, Kin; Lo, Amy Cheuk-Yin; Tsao, Sai-Wah; Kok, Kin-Hang; Jin, Dong-Yan; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2016-01-01

    Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (⩾2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF-1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV. PMID:27553173

  4. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling

    PubMed Central

    Knöfler, Martin; Pollheimer, Jürgen

    2013-01-01

    Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signaling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signaling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β -catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signaling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signaling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β -catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signaling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodeling. Moreover, changes in Wnt signaling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signaling in physiological and abnormal trophoblast function. PMID

  5. Development and characterization of a monoclonal antibody to human embryonal carcinoma

    SciTech Connect

    Khazaeli, M.B.; Beierwaltes, W.H.; Pitt, G.S.; Kabza, G.A.; Rogers, K.J.; LoBuglio, A.F.

    1987-06-01

    A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with /sup 131/I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21.

  6. Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2.

    PubMed

    Fahlbusch, Fabian B; Ruebner, Matthias; Huebner, Hanna; Volkert, Gudrun; Bartunik, Hannah; Winterfeld, Ilona; Hartner, Andrea; Menendez-Castro, Carlos; Noegel, Stephanie C; Marek, Ines; Wachter, David; Schneider-Stock, Regine; Beckmann, Matthias W; Kehl, Sven; Rascher, Wolfgang

    2015-09-01

    Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology. PMID:26070363

  7. Primary intracranial choriocarcinoma: MR imaging findings.

    PubMed

    Lv, X-F; Qiu, Y-W; Zhang, X-L; Han, L-J; Qiu, S-J; Xiong, W; Wen, G; Zhang, Y-Z; Zhang, J

    2010-11-01

    PICCC is the rarest, most malignant primary intracranial GCT. The purpose of this study was to describe and characterize the MR imaging findings in a series of 7 patients (6 males and 1 female; mean age, 11.9 years) with pathologically proved PICCC in our institution from 2004 to 2009. All tumors were located within the pineal (n = 6) or suprasellar (n = 1) regions. On T2-weighted MR imaging, the lesions appeared markedly heterogeneous with areas of both hypointensity and hyperintensity reflecting the histologic heterogeneity, including hemorrhage, fibrosis, cysts, or necrosis. Heterogeneous (n = 7), ringlike (n = 4), and/or intratumoral nodular (n = 3) enhancement was noted on T1-weighted images with gadolinium. These MR imaging findings, combined with patient age and serum β-HCG levels, may prove helpful in distinguishing PICCC from the more common primary brain tumors, thereby avoiding biopsy of this highly vascular tumor. PMID:20616180

  8. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity

    SciTech Connect

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [{sup 3}H]{sub 2}O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks

  9. Involvement of GATA transcription factors in the regulation of endogenous bovine interferon-tau gene transcription.

    PubMed

    Bai, Hanako; Sakurai, Toshihiro; Kim, Min-Su; Muroi, Yoshikage; Ideta, Atsushi; Aoyagi, Yoshito; Nakajima, Hiromi; Takahashi, Masashi; Nagaoka, Kentaro; Imakawa, Kazuhiko

    2009-12-01

    Expression of interferon-tau (IFNT), necessary for pregnancy establishment in ruminant ungulates, is regulated in a temporal and spatial manner. However, molecular mechanisms by which IFNT gene transcription is regulated in this manner have not been firmly established. In this study, DNA microarray/RT-PCR analysis between bovine trophoblast CT-1 and Mardin-Darby bovine kidney (MDBK) cells was initially performed, finding that transcription factors GATA2, GATA3, and GATA6 mRNAs were specific to CT-1 cells. These mRNAs were also found in Days 17, 20, and 22 (Day 0 = day of estrus) bovine conceptuses. In examining other bovine cell lines, ovary cumulus granulosa (oCG) and ear fibroblast (EF) cells, GATA2 and GATA3, but not GATA6, were found specific to the bovine trophoblast cells. In transient transfection analyses using the upstream region (-631 to +59 bp) of bovine IFNT gene (bIFNT, IFN-tau-c1), over-expression of GATA2/GATA3 did not affect the transcription of bIFNT-reporter construct in human choriocarcinoma JEG3 cells. Transfection of GATA2, GATA3, ETS2, and/or CDX2, however, was effective in the up-regulation of the bIFNT construct transfected into bovine oCG and EF cells. One Point mutation studies revealed that among six potential GATA binding sites located on the upstream region of the bIFNT gene, the one next to ETS2 site exhibited reduced luciferase activity. In CT-1 cells, endogenous bIFNT gene transcription was up-regulated by over-expression of GATA2 or GATA3, but down-regulated by siRNA specific to GATA2 mRNA. These data suggest that GATA2/3 is involved in trophoblast-specific regulation of bIFNT gene transcription. PMID:19598245

  10. Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the Pre-attachment Period in Sheep.

    PubMed

    Kim, Min-Su; Sakurai, Toshihiro; Bai, Hanako; Bai, Rulan; Sato, Daisuke; Nagaoka, Kentaro; Chang, Kyu-Tae; Godkin, James D; Min, Kwan-Sik; Imakawa, Kazuhiko

    2013-05-01

    Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants. PMID:25049833

  11. A Novel Feeder-Free Culture System for Human Pluripotent Stem Cell Culture and Induced Pluripotent Stem Cell Derivation

    PubMed Central

    Vuoristo, Sanna; Toivonen, Sanna; Weltner, Jere; Mikkola, Milla; Ustinov, Jarkko; Trokovic, Ras; Palgi, Jaan; Lund, Riikka; Tuuri, Timo; Otonkoski, Timo

    2013-01-01

    Correct interactions with extracellular matrix are essential to human pluripotent stem cells (hPSC) to maintain their pluripotent self-renewal capacity during in vitro culture. hPSCs secrete laminin 511/521, one of the most important functional basement membrane components, and they can be maintained on human laminin 511 and 521 in defined culture conditions. However, large-scale production of purified or recombinant laminin 511 and 521 is difficult and expensive. Here we have tested whether a commonly available human choriocarcinoma cell line, JAR, which produces high quantities of laminins, supports the growth of undifferentiated hPSCs. We were able to maintain several human pluripotent stem cell lines on decellularized matrix produced by JAR cells using a defined culture medium. The JAR matrix also supported targeted differentiation of the cells into neuronal and hepatic directions. Importantly, we were able to derive new human induced pluripotent stem cell (hiPSC) lines on JAR matrix and show that adhesion of the early hiPSC colonies to JAR matrix is more efficient than to matrigel. In summary, JAR matrix provides a cost-effective and easy-to-prepare alternative for human pluripotent stem cell culture and differentiation. In addition, this matrix is ideal for the efficient generation of new hiPSC lines. PMID:24098444

  12. Human placental cell and tissue uptake of doxorubicin and its liposomal formulations.

    PubMed

    Soininen, Suvi K; Repo, Jenni K; Karttunen, Vesa; Auriola, Seppo; Vähäkangas, Kirsi H; Ruponen, Marika

    2015-12-01

    The anticancer drug doxorubicin and its liposomal formulations are in clinical use, doxorubicin also during pregnancy. However, little is known about how doxorubicin and its liposomal formulations are taken up by placental cells and whether they can cross human placenta. We therefore investigated quantitative cellular uptake and toxicity of doxorubicin and its two liposomal formulations, pH-sensitive liposomal doxorubicin (L-DOX) and commercially available pegylated liposomal doxorubicin (PL-DOX), in human placental choriocarcinoma (BeWo) cells. PL-DOX showed significantly lower cellular uptake and toxicity compared with doxorubicin and L-DOX. In preliminary studies with human placental perfusion, PL-DOX did not cross the placenta at all in 4h, whereas doxorubicin and L-DOX crossed the placenta at low levels (max 12% of the dose). Furthermore, PL-DOX did not accumulate in placental tissue while doxorubicin did (up to 70% of the dose). Surface pegylation probably explains the low placental cell and tissue uptake of PL-DOX. Formulation of doxorubicin thus seems to enable a decrease of fetal exposure. PMID:26383631

  13. Differential Regulation of Human 3β-Hydroxysteroid Dehydrogenase Type 2 for Steroid Hormone Biosynthesis by Starvation and Cyclic Amp Stimulation: Studies in the Human Adrenal NCI-H295R Cell Model

    PubMed Central

    Hofer, Gaby; Mullis, Primus E.; Flück, Christa E.

    2013-01-01

    Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs). Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6–8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute) versus long-term (chronic) stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression. PMID:23874725

  14. A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance

    PubMed Central

    McConkey, Cameron A.; Delorme-Axford, Elizabeth; Nickerson, Cheryl A.; Kim, Kwang Sik; Sadovsky, Yoel; Boyle, Jon P.; Coyne, Carolyn B.

    2016-01-01

    In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)–based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance. PMID:26973875

  15. Evaluation of nicked human chorionic gonadotropin content in clinical specimens by a specific immunometric assay.

    PubMed

    Kovalevskaya, G; Birken, S; Kakuma, T; Schlatterer, J; O'Connor, J F

    1999-01-01

    We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made. PMID:9895340

  16. Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro

    PubMed Central

    Jones, H.; Crombleholme, T.; Habli, M.

    2014-01-01

    Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor-11 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined amino acid transporter expression and localization in both a mouse model of placental Insufficiency (PI) and a model of human trophoblast, the BeWo Choriocarcinoma cell line. For in vitro human studies, BeWo Choriocarcinoma cells were maintained in F12 complete medium + 10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 h. MOIs of 10:1 and 100:1 were utilized. In BeWo, transfection efficiency was 100% at an MOI of 100:1 and Ad-IGF-1 significantly increased IGF-1 secretion, proliferation and invasion but reduced apoptosis compared to controls. In vitro, amino acid uptake was increased following Ad-IGF-1 treatment and associated with significantly increased RNA expression of SNAT1, 2, LAT1 and 4F2hc. Only SNAT2 protein expression was increased but LAT1 showed relocalization from a perinuclear location to the cytoplasm and cell membrane. For in vivo studies, timed-pregnant animals were divided into four groups on day 18; sham-operated controls, uterine artery branch ligation (UABL), UABL + Ad-hIGF-1 (108 PFU), UABL + Ad-LacZ (108 PFU). At gestational day 20, pups and placentas were harvested by C-section. Only LAT1 mRNA expression changed, showing that a reduced expression of the transporter levels in the PI model could be partially rectified with Ad-hIGF1 treatment. At the protein level, System L was reduced in PI but remained at control levels following Ad-hIGF1. The System A isoforms were differentially regulated with SNAT2 expression diminished but SNAT1 increased in PI and Ad-hIGF1 groups. Enhanced

  17. miR-34a expression, epigenetic regulation, and function in human placental diseases

    PubMed Central

    Doridot, Ludivine; Houry, Dorothée; Gaillard, Harald; Chelbi, Sonia T; Barbaux, Sandrine; Vaiman, Daniel

    2014-01-01

    Preeclampsia (PE) is the major pregnancy-induced hypertensive disorder responsible for maternal and fetal morbidity and mortality that can be associated with intrauterine growth restriction (IUGR). PE and IUGR are thought to be due to a placental defect, occurring early during pregnancy. Several placental microRNAs (miRNAs) have been shown to be deregulated in the context of placental diseases and could thus play a role in the pathophysiology of PE. Here, we show that pri-miR-34a is overexpressed in preeclamptic placentas and that its placental expression is much higher during the first trimester of pregnancy than at term, suggesting a possible developmental role. We explored pri-miR-34a regulation and showed that P53, a known activator of miR-34a, is reduced in all pathological placentas and that hypoxia can induce pri-miR-34a expression in JEG-3 cells. We also studied the methylation status of the miR-34a promoter and revealed hypomethylation in all preeclamptic placentas (associated or not with IUGR), whereas hypoxia induced a hypermethylation in JEG-3 cells at 72 h. Despite the overexpression of pri-miR-34a in preeclampsia, there was a striking decrease of the mature miR-34a in this condition, suggesting preeclampsia-driven alteration of pri-miR-34a maturation. SERPINA3, a protease inhibitor involved in placental diseases, is elevated in IUGR and PE. We show here that miR-34a overexpression in JEG-3 downregulates SERPINA3. The low level of mature miR-34a could thus be an important mechanism contributing to SERPINA3 upregulation in placental diseases. Overall, our results support a role for miR-34a in the pathophysiology of preeclampsia, through deregulation of the pri-miRNA expression and its altered maturation. PMID:24081307

  18. 12-O-tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Sp1 sites.

    PubMed

    Coles, R; Birdsall, M; Wyttenbach, A; Rubinsztein, D C

    2000-09-28

    We have studied the effects of the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on Huntington's disease (HD) gene transcription in neuronal and non-neuronal cell lines, to investigate pathways regulating HD gene expression. TPA reduced transcription from the HD gene promoter in SK-N-SH (neuroblastoma) and HeLa cells but not in JEG3 (choriocarcinoma) cells. In SK-N-SH cells, the responsible cis-acting promoter sequences comprise the tandemly duplicated Sp1 sites in the region from -213 to -174, relative to the translation start site. The TPA-down-regulating region in HeLa cells was mapped to the sequence from -141 to -126. In conclusion, this demonstrates that HD gene transcription can be down-regulated in vitro in a cell-specific manner. PMID:11043541

  19. HUMAN CYTOSOLIC SULFOTRANSFERASE 2B1: ISOFORM EXPRESSION, TISSUE SPECIFICITY AND SUBCELLULAR LOCALIZATION

    PubMed Central

    Falany, C.N.; He, D.; Dumas, N.; Frost, A.R.; Falany, J.L.

    2007-01-01

    Sulfation is an important Phase II conjugation reaction involved in the synthesis and metabolism of steroids in humans. Two different isoforms (2B1a and 2B1b) are encoded by the sulfotransferase (SULT) 2B1 gene utilizing different start sites of transcription resulting in the incorporation of different first exons. SULT2B1a and SULT2B1b are 350 and 365 amino acids in length, respectively, and the last 342 aa are identical. Message for both SULT2B1 isoforms is present in human tissues although SULT2B1b message is generally more abundant. However, to date only SULT2B1b protein has been detected in human tissues or cell lines. SULT2B1b is localized in the cytosol and/or nuclei of human cells. A unique 3′-extension of SULT2B1b is required for nuclear localization in human BeWo placental choriocarcinoma cells. Nuclear localization is stimulated by forskolin treatment in BeWo cells and serine phosphorylation has been identified in the 3′-extension. SULT2B1b is selective for the sulfation of 3β-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and may also have a role in cholesterol sulfation in human skin. The substrate specificity, nuclear localization, and tissue localization of SULT2B1b suggest a role in regulating the responsiveness of cells to adrenal androgens via their direct inactivation or by preventing their conversion to more potent androgens and estrogens. PMID:17055258

  20. CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues

    SciTech Connect

    Matouskova, Magda; Blazkova, Jana; Pajer, Petr; Pavlicek, Adam; Hejnar, Jiri . E-mail: hejnar@img.cas.cz

    2006-04-15

    Syncytin-1 is a captive envelope glycoprotein encoded by one of human endogenous retroviruses W. It is expressed exclusively in the placental trophoblast where it participates in cell-to-cell fusion during differentiation of syncytiotrophobast. In other tissues, however, syncytin-1 expression must be kept in check because inadvertent cell fusion might be dangerous for tissue organization and integrity. We describe here an inverse correlation between CpG methylation of syncytin-1 5' long terminal repeat and its expression. Hypomethylation of the syncytin-1 5' long terminal repeat in the placenta and in the choriocarcinoma-derived cell line BeWo was detected. However, other analyzed primary cells and cell lines non-expressing syncytin-1 contain proviruses heavily methylated in this sequence. CpG methylation of syncytin-1 is resistant to the effect of the demethylating agent 5-azacytidine. The inhibitory role of CpG methylation is further confirmed by transient transfection of in-vitro-methylated syncytin-1 promoter-driven reporter construct. Altogether, we conclude that CpG methylation plays a principal role in the transcriptional suppression of syncytin-1 in non-placental tissues, and, in contrast, demethylation of the syncytin-1 promoter in trophoblast is a prerequisite for its expression and differentiation of multinucleated syncytiotrophoblast.

  1. Regulation of cytochrome b5 gene transcription by Sp3, GATA-6, and steroidogenic factor 1 in human adrenal NCI-H295A cells.

    PubMed

    Huang, Ningwu; Dardis, Andrea; Miller, Walter L

    2005-08-01

    Sex steroid synthesis requires the 17,20 lyase activity of P450c17, which is enhanced by cytochrome b5, acting as an allosteric factor to promote association of P450c17 with its electron donor, P450 oxidoreductase. Cytochrome b5 is preferentially expressed in the fetal adrenal and postadrenarchal adrenal zona reticularis; the basis of this tissue-specific, developmentally regulated transcription of the b5 gene is unknown. We found b5 expression in all cell lines tested, including human adrenal NCI-H295A cells, where its mRNA is reduced by cAMP and phorbol ester. Multiple sites, between -83 and -122 bp upstream from the first ATG, initiate transcription. Deletional mutagenesis localized all detectable promoter activity within -327/+15, and deoxyribonuclease I footprinting identified protein binding at -72/-107 and -157/-197. DNA segments -65/-40, -114/-70 and -270/-245 fused to TK32/Luc yielded significant activity, and mutations in their Sp sites abolished that activity; electrophoretic mobility shift assay (EMSA) showed that Sp3, but not Sp1, binds to these Sp sites. Nuclear factor 1 (NF-1) and GATA-6, but not GATA-4 bind to the NF-1 and GATA sites in -157/-197. In Drosophila S2 cells, Sp3 increased -327/Luc activity 58-fold, but Sp1 and NF-1 isoforms were inactive. Mutating the three Sp sites ablated activity without or with cotransfection of Sp1/Sp3. In NCI-H295A cells, mutating the three Sp sites reduced activity to 39%; mutating the Sp, GATA, and NF-1 sites abolished activity. In JEG-3 cells, GATA-4 was inactive, GATA-6 augmented -327/Luc activity to 231% over the control, and steroidogenic factor 1 augmented activity to 655% over the control; these activities required the Sp and NF-1 sites. Transcription of cytochrome b5 shares many features with the regulation of P450c17, whose activity it enhances. PMID:15831526

  2. Up-regulation of placental leptin by human chorionic gonadotropin.

    PubMed

    Maymó, Julieta L; Pérez Pérez, Antonio; Sánchez-Margalet, Víctor; Dueñas, José L; Calvo, Juan Carlos; Varone, Cecilia L

    2009-01-01

    Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 microM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 microm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction

  3. Acanthamoeba royreba sp. n. from a human tumor cell culture.

    PubMed

    Willaert, E; Stevens, A R; Tyndall, R L

    1978-02-01

    A new species of Acanthamoeba was isolated from a culture of an established line of human choriocarcinoma cells. The identification of this strain, originally called the Oak Ridge strain, and the establishment of a new species for it were based on morphologic, serologic, and immunochemical studies. In general, the structure of the trophozoite did not differ significantly from that of other species of Acanthamoeba, except that a body which more closely resembled a centriole than material described previously as centriolar satellites was observed in trophozoites examined with the electron microscope. The dimensions of the trophozoite were the smallest among the species of Acanthamoeba. The cyst was typical of the genus, but differed from those of other species by its smaller size and the presence of numerous ostioles. Studies of the Oak Ridge strain by immunofluorescence using antisera developed against the isolate and Acanthamoeba culbertsoni, A. castellanii, A. polyphaga, A. rhysodes, A. astronyxis, and A. palestinensis revealed the antigenic uniqueness of the Oak Ridge strain. It was demonstrated by immunoelectrophoretic analyses of the soluble proteins of the Oak Ridge strain that shared approximately 1/2 of its antigenic structure with A. castellanii and A. culbertsoni. The antigenic differences of the isolate from other species of Acanthamoeba were deduced from comparison of the antigenic constitution of these species and the Oak Ridge strain with A. culbertsoni and A. castellanii. Although the strain was initially recognized by its cytopathogenicity for cultures, it did not produce acute infections in mice after intranasal inoculation of 1 X 10(4) ameba/mouse. The foregoing results constituted the basis for the establishment of the Oak Ridge strain as a new species, A. royreba sp. n., in the genus Acanthamoeba. PMID:566323

  4. Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells.

    PubMed

    Shields-Botella, J; Chetrite, G; Meschi, S; Pasqualini, J R

    2005-01-01

    androstenedione to E(1) in the aromatase-rich choriocarcinoma cell line JEG-3. In conclusion, the inhibitory effect provoked by NOMAC on the enzymes involved in the biosynthesis of E(2) (sulfatase and 17HSD pathways) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive E(1)S, can open attractive perspectives for future clinical trials. PMID:15748827

  5. Cyclic AMP regulation of the human glycoprotein hormone. cap alpha. -subunit gene is mediated by an 18-base-pair element

    SciTech Connect

    Silver, B.J.; Bokar, J.A.; Virgin, J.B.; Vallen, E.A.; Milsted, A.; Nilson, J.H.

    1987-04-01

    cAMP regulates transcription of the gene encoding the ..cap alpha..-subunit of human chorionic gonadotropin (hCG) in the choriocarcinoma cells (BeWo). To define the sequences required for regulation by cAMP, the authors inserted fragments from the 5' flanking region of the ..cap alpha..-subunit gene into a test vector containing the simian virus 40 early promoter (devoid of its enhancer) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Results from transient expression assays in BeWo cells indicated that a 1500-base-pair (bp) fragment conferred cAMP responsiveness on the CAT gene regardless of position or orientation of the insert relative to the viral promoter. A subfragment extending from position -169 to position -100 had the same effect on cAMP-induced expression. Furthermore, the entire stimulatory effect could be achieved with an 18-bp synthetic oligodeoxynucleotide corresponding to a direct repeat between position -146 and -111. In the absence of cAMP, the ..cap alpha..-subunit 5' flanking sequence also enhanced transcription from the simian virus 40 early promoter. They localized this enhancer activity to the same -169/-100 fragment containing the cAMP response element. The 18-bp element alone, however, had no effect on basal expression. Thus, this short DNA sequence serves as a cAMP response element and also functions independently of other promoter-regulatory elements located in the 5' flanking sequence of the ..cap alpha..-subunit gene.

  6. Interaction between human placental microvascular endothelial cells and a model of human trophoblasts: effects on growth cycle and angiogenic profile.

    PubMed

    Troja, Weston; Kil, Kicheol; Klanke, Charles; Jones, Helen N

    2014-01-01

    Abstract Intrauterine growth restriction (IUGR) is a leading cause of perinatal complications, and is commonly associated with reduced placental vasculature. Recent studies demonstrated over-expression of IGF-1 in IUGR animal models maintains placental vasculature. However, the cellular environment of the placental chorionic villous is unknown. The close proximity of trophoblasts and microvascular endothelial cells in vivo alludes to autocrine/paracrine regulation following Ad-HuIGF-1 treatment. We investigated the co-culturing of BeWo Choriocarcinoma and Human Placental Microvascular Endothelial Cells (HPMVECs) on the endothelial angiogenic profile and the effect Ad-HuIGF-1 treatment of one cell has on the other. HPMVECs were isolated from human term placentas and cultured in EGM-2 at 37°C with 5% CO2. BeWo cells were maintained in Ham's F12 nutrient mix with 10% FBS and 1% pen/strep. Co-cultured HPMVECS+BeWo cells were incubated in serum-free control media, Ad-HuIGF-1, or Ad-LacZ at MOI 0 and MOI 100:1 for 48 h. Non-treated cells and mono-cultured cells were compared to co-cultured cells. Angiogenic gene expression and proliferative and apoptotic protein expression were analysed by RT-qPCR and immunocytochemistry, respectively. Statistical analyses was performed using student's t-test with P < 0.05 considered significant. Direct Ad-HuIGF-1 treatment increased HPMVEC proliferation (n = 4) and reduced apoptosis (n = 3). Co-culturing HPMVECs+BeWo cells significantly altered RNA expression of the angiogenic profile compared to mono-cultured HPMVECs (n = 8). Direct Ad-HuIGF-1 treatment significantly increased Ang-1 (n = 4) in BeWo cells. Ad-HuIGF-1 treatment of HPMVECs did not alter the RNA expression of angiogenic factors. Trophoblastic factors may play a key role in placental vascular development and IGF-1 may have an important role in HPMVEC growth. PMID:24760505

  7. Membrane potential difference and intracellular cation concentrations in human placental trophoblast cells in culture.

    PubMed Central

    Greenwood, S L; Clarson, L H; Sides, M K; Sibley, C P

    1996-01-01

    1. The electrochemical gradients for Na+ and K+ were assessed in a cell culture model of trophoblast differentiation. 2. Membrane potential difference (Em), intracellular water and Na+ and K+ contents were measured in choriocarcinoma cells (JAr cell line; 96% of which are undifferentiated trophoblast cells) and in mononucleate and multinucleate (differentiated) cytotrophoblast cells isolated from the human placenta at term. 3. There was a significant fall in Em from -57 mV in JAr cells, to -48 and -40 mV in mono-and multinucleate cytotrophoblast cells, respectively. Treatment with ouabain (1 mM for 15 min) depolarized the JAr cell membrane by 15 mV but did not affect cytotrophoblast cell membrane potential. 4. Intracellular K+ concentration was similar in JAr, mono- and multinucleate cytotrophoblast cells but Na+ concentration was higher in mononucleate cytotrophoblast cells compared with JAr cells. 5. Ouabain treatment (3 mM for 15 min) caused a small increase (4.5%) in cell water in mononucleate cytotrophoblast cells but lowered K+ (approximately 30%) and increased Na+ concentration (approximately 125%) in all the trophoblast cells studied. 6. The K+ equilibrium potential (EK) was more negative than Em in all cells and the difference between EK and Em was smaller in JAr cells (-25 mV) than in mono- and multinucleate cytotrophoblast cells (-33 and -43 mV, respectively). 7. The Na+ equilibrium potential (ENa) was positive in the trophoblast cells and the difference between ENa and Em was 122, 100 and 100 mV in JAr, mono- and multinucleate cytotrophoblast cells, respectively. 8. These results suggest that the electrochemical gradient for K+ is affected by the stage of trophoblast cell differentiation. In contrast, the electrochemical gradient for Na+ is similar in mono- and multinucleate cytotrophoblast cells. Images Figure 1 PMID:8734977

  8. Human See, Human Do.

    ERIC Educational Resources Information Center

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  9. Hypericum caprifoliatum and Hypericum connatum affect human trophoblast-like cells differentiation and Ca2+ influx

    PubMed Central

    da Conceição, Aline O.; von Poser, Gilsane Lino; Barbeau, Benoit; Lafond, Julie

    2014-01-01

    Objective To study the effect of crude methanol and n-hexane extracts of Hypericum connatum (H. connatum) and Hypericum caprifoliatum on trophoblast-like cells. Methods BeWo and JEG-3 trophoblast-like cells were submitted to different extract concentrations (1, 5, 10 and 15 µg/mL) and evaluated in relation to cell viability and in vitro trophoblast differentiation and function. Cell viability was evaluated using WST-1 reagent. Differentiation was measured by luciferase production, hCG production/release, and mitogen-activated protein kinase signaling pathway activation. The function of the trophoblast-like cells was measured by 45Ca2+ influx evaluation. Results The results showed a decrease in cell viability/proliferation. Both plants and different extracts induced a significant decrease in hCG production/release and luciferase production. H. connatum did not cause mitogen-activated protein kinase signaling pathway disturbance; however, Hypericum caprifoliatum n-hexane extract at 15 µg/mL inhibited extracellular signal-regulated kinase 1/2 activation. The significant increase in Ca2+ influx by JEG-3 cells was seen after short and long incubation times with H. connatum methanolic extract at 15 µg/mL. Conclusions The results indicated that these two Hypericum species extracts can interfere on trophoblast differentiation and Ca2+ influx, according to their molecular diversity. Although in vivo experiments are necessary to establish their action on placental formation and function, this study suggests that attention must be paid to the potential toxic effect of these plants. PMID:25182721

  10. Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion

    PubMed Central

    Chen, Haiying; Sun, Manni; Liu, Jing; Tong, Chunxiao; Meng, Tao

    2015-01-01

    Paternally expressed gene 10 (PEG10) is an imprinted and monoallelic expressed gene. Previous study using a knockout mouse model revealed a crucial role of PEG10 in placental development, yet the exact function of PEG10 during placentation remains to be elucidated. In this study, denuded chorionic villi were prepared from first trimester human placentas, and transduced with PEG10 small interference RNA (siRNA) or non-targeting control sequence by lentiviral infection. Immunohistochemical staining revealed that silencing of PEG10 in the chorionic villous explants resulted in reduced immune-reactivity to CK7, Ki67 and integrin α5, implying that silencing of PEG10 impaired the proliferation of villous trophoblasts and may interfere with the activity of extravillous trophoblasts. We further investigated the role of PEG10 in the proliferation, migration and invasion of JEG-3 trophoblast cell line and the primary chorionic villous cells. PEG10-silenced JEG-3 cells and primary chorionic villous cells displayed a reduced proliferation rate and impaired invasiveness in vitro. Silencing of PEG10 in trophoblast cells led to upregulated expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as downregulated expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, knockdown of TIMP-1 reversed the suppressed invasiveness of PEG10 siRNA-transduced JEG-3 cells. In conclusion, our study demonstrates that PEG10 plays an important role in trophoblast proliferation and promotes trophoblast invasion through TIMP-1. PMID:26680220

  11. Human Development, Human Evolution.

    ERIC Educational Resources Information Center

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a wholly new…

  12. Human Health

    MedlinePlus

    ... effects of climate change Video not supported Human Health Climate change threatens human health and well-being ... Copy link to clipboard Key Message: Wide-ranging Health Impacts Climate change threatens human health and well- ...

  13. Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production.

    PubMed

    Fournier, Thierry

    2016-06-01

    Human chorionic gonadotropin (hCG) is the first hormonal message from the placenta to the mother. It is detectable in maternal blood two days after implantation and behaves like a super LH agonist stimulating progesterone secretion by the corpus luteum. In addition to maintaining the production of progesterone until the placenta itself produces it, hCG also has a role in myometrial quiescence and local immune tolerance. Specific to humans, hCG is a complex glycoprotein composed of two highly glycosylated subunits. The α-subunit is identical to the pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene (CGA). By contrast, the β-subunits are distinct for each hormones and confer both receptor and biological specificity, although LH and hCG bind to the same receptor (LH/CG-R). The hCG ß-subunit is encoded by a cluster of genes (CGB) and contains two sites of N-glycosylation and four sites of O-glycosylation. The hCG glycosylation state varies with the stage of pregnancy, its source of production and in the pathology. It is well established that hCG is mainly secreted into maternal blood, where it peaks at 8-10weeks of gestation (WG), by the syncytiotrophoblast (ST), which represents the endocrine tissue of the human placenta. The invasive extravillous trophoblast (iEVT) also secretes hCG, and in particular hyperglycosylated forms of hCG (hCG-H) also produced by choriocarcinoma cells. In maternal blood, hCG-H is elevated during early first trimester corresponding to the trophoblastic cell invasion process and then decreases. In addition to its endocrine role, hCG has autocrine and paracrine roles. It promotes formation of the ST and angiogenesis through LH/CG-R but has no effect on trophoblast invasion in vitro. By contrast, hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGFß receptor in a LH/CG-R independent signalling pathway. hCG is largely used in antenatal screening

  14. Down-Regulation of S100A11, a Calcium-Binding Protein, in Human Endometrium May Cause Reproductive Failure

    PubMed Central

    Liu, Xin-Mei; Ding, Guo-Lian; Jiang, Ying; Pan, Hong-Jie; Zhang, Dan; Wang, Ting-Ting; Zhang, Run-Ju; Shu, Jing

    2012-01-01

    Background: Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses. Objectives: The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. Methods: S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA. Results: S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11. Conclusions: Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S

  15. Cloning of a cDNA encoding a putative human very low density lipoprotein/Apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23[sup 6

    SciTech Connect

    Gafvels, M.E.; Strauss, J.F. III ); Caird, M.; Patterson, D. ); Britt, D.; Jackson, C.L. )

    1993-11-01

    The authors report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/[alpha][sub 2]-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. The results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.

  16. New discoveries on the biology and detection of human chorionic gonadotropin

    PubMed Central

    Cole, Laurence A

    2009-01-01

    Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic

  17. Determination of hyperglycosylated human chorionic gonadotropin produced by malignant gestational trophoblastic neoplasias and male germ cell tumors using a lectin-based immunoassay and surface plasmon resonance

    PubMed Central

    Kelly, Lisa S.; Birken, Steven; Puett, David

    2007-01-01

    The ability to reliably detect aberrant glycosylation of human chorionic gonadotropin (hCG) may have profound implications for the diagnosis and monitoring of malignant gestational trophoblastic neoplasia, germ cell tumors, other malignancies, and pregnancy complications. To become a clinically useful assay, however, this discrimination of glycoforms should be possible on minimally treated biological specimens. Towards this end, we have developed a lectin-based sandwich-type immunoassay to compare the glycosylation patterns of hCG among urine specimens from patients presenting with a normal pregnancy, invasive mole, choriocarcinoma, and male germ cell tumors using carbohydrate-free antibody fragments as capture reagents and a panel of eight lectins, five recognizing neutral sugars and three recognizing sialic acid. There was no significant difference in the binding of any of the lectins to hCG in the urine of women over the gestational range of 6 – 38 weeks. Three lectins, however, exhibited differential binding to urinary hCG derived from these normal pregnant controls and that from patients with malignant forms of gestational trophoblastic disease and male germ cell tumors. Galanthus nivalis agglutinin and Maackia amurensis lectin, which bind terminal mannose and α(2–3)sialic acid, respectively, preferentially bound pregnancy-derived hCG, whereas the lectin, wheat germ agglutinin, which binds sialic acid and β(1–4)N-acetylglucosamine, exhibited decreased binding to pregnancy-derived hCG compared to that from patients with male germ cell tumors and malignant gestational trophoblastic neoplasia. The differential binding observed with these three promising lectins is most encouraging and warrants further examination. The experimental paradigm also holds promise for the development of comparable assays for other glycosylated tumor markers. PMID:17081681

  18. Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration

    PubMed Central

    Salomon, Carlos; Yee, Sarah; Scholz-Romero, Katherin; Kobayashi, Miharu; Vaswani, Kanchan; Kvaskoff, David; Illanes, Sebastian E.; Mitchell, Murray D.; Rice, Gregory E.

    2014-01-01

    Background: Vascular smooth muscle cells (VSMCs) migration is a critical process during human uterine spiral artery (SpA) remodeling and a successful pregnancy. Extravillous trophoblast cells (EVT) interact with VSMC and enhance their migration, however, the mechanisms by which EVT remodel SpA remain to be fully elucidated. We hypothesize that exosomes released from EVT promote VSMC migration. Methods: JEG-3 and HTR-8/SVneo cell lines were used as models for EVT. Cells were cultured at 37°C and humidified under an atmosphere of 5% CO2-balanced N2 to obtain 8% O2. Cell-conditioned media were collected, and exosomes (exo-JEG-3 and exo- HTR-8/SVneo) isolated by differential and buoyant density centrifugation. The effects of exo-EVT on VSMC migration were established using a real-time, live-cell imaging system (Incucyte™). Exosomal proteins where identified by mass spectrometry and submitted to bioinformatic pathway analysis (Ingenuity software). Results: HTR-8/SVneo cells were significantly more (~30%) invasive than JEG-3 cells. HTR-8/SVneo cells released 2.6-fold more exosomes (6.39 × 108 ± 2.5 × 108 particles/106 cells) compared to JEG-3 (2.86 × 108 ± 0.78 × 108 particles/106 cells). VSMC migration was significantly increased in the presence of exo-JEG-3 and exo-HTR-8/SVneo compared to control (−exosomes) (21.83 ± 0.49 h and 15.57 ± 0.32, respectively, vs. control 25.09 ± 0.58 h, p < 0.05). Sonication completely abolished the effect of exosomes on VSMC migration. Finally, mass spectrometry analysis identified unique exosomal proteins for each EVT cell line-derived exosomes. Conclusion: The data obtained in this study are consistent with the hypothesis that the release, content, and bioactivity of exosomes derived from EVT-like cell lines is cell origin-dependent and differentially regulates VSMC migration. Thus, an EVT exosomal signaling pathway may contribute to SpA remodeling by promoting the migration of VSMC out of the vessel walls. PMID:25157233

  19. Human Trafficking

    MedlinePlus

    ... to debt bondage or peonage in which traffickers demand labor as a means repayment for a real ... human smuggling are two separate crimes under federal law. There are several important differences between them. Human ...

  20. Human Trafficking

    MedlinePlus

    ... TRAFFICKING (English) Listen < Back to Search FACT SHEET: HUMAN TRAFFICKING (English) Published: August 2, 2012 Topics: Public Awareness , ... organizations that protect and serve trafficking victims. National Human Trafficking Resource Center at 1.888.373.7888 Last ...

  1. Human Issues in Human Rights

    ERIC Educational Resources Information Center

    Kates, Robert W.

    1978-01-01

    Presents the report of the National Academy of Sciences' Committee in Human Rights which seeks to ease the plight of individual scientists, engineers, and medical personnel suffering severe repression. Case studies of instances of negligence of human rights are provided. (CP)

  2. Quantifying the Biomechanics of Conception: L-Selectin-Mediated Blastocyst Implantation Mechanics with Engineered “Trophospheres”

    PubMed Central

    Jost, Monika; Rothstein, Dianne; Robertson, Noreen; Marcolongo, Michele S.

    2014-01-01

    An estimated 12% of women in the United States suffer from some form of infertility. In vitro fertilization (IVF) is the most common treatment for infertility encompassing over 99% of all assisted reproductive technologies. However, IVF has a low success rate. Live birth rates using IVF can range from 40% in women younger than 35 years to 4% in women older than 42 years. Costs for a successful IVF outcome can be upward of $61,000. The low success rate of IVF has been attributed to the inability of the blastocyst to implant to the uterus. Blastocyst implantation is initiated by L-selectin expressing cells, trophoblasts, binding to L-selectin ligands, primarily sialyl Lewis X (sLeX), on the uterine surface endometrium. Legal and ethical considerations have limited the research on human subjects and tissues, whereas animal models are costly or do not properly mimic human implantation biochemistry. In this work, we describe a cellular model system for quantifying L-selectin adhesion mechanics. L-selectin expression was confirmed in Jeg-3, JAR, and BeWo cell lines, with only Jeg-3 cells exhibiting surface expression. Jeg-3 cells were cultured into three-dimensional spheres, termed “trophospheres,” as a mimic to human blastocysts. Detachment assays using a custom-built parallel plate flow chamber show that trophospheres detach from sLeX functionalized slides with 2.75×10−3 dyn of force and 7.5×10−5 dyn-cm of torque. This work marks the first time a three-dimensional cell model has been utilized for quantifying L-selectin binding mechanics related to blastocyst implantation. PMID:23927766

  3. Action, human.

    PubMed

    Russo, M T

    2010-01-01

    The term "human action" designates the intentional and deliberate movement that is proper and exclusive to mankind. Human action is a unified structure: knowledge, intention or volition, deliberation, decision or choice of means and execution. The integration between these dimensions appears as a task that demands strength of will to achieve the synthesis of self-possession and self-control that enables full personal realisation. Recently, the debate about the dynamism of human action has been enriched by the contribution of neurosciences. Thanks to techniques of neuroimaging, neurosciences have expanded the field of investigation to the nature of volition, to the role of the brain in decision-making processes and to the notion of freedom and responsibility. PMID:20393686

  4. Human Trafficking

    ERIC Educational Resources Information Center

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  5. Nothing Human

    ERIC Educational Resources Information Center

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  6. Classical Humanities

    ERIC Educational Resources Information Center

    Goodwin, Donn; And Others

    1975-01-01

    This article reports on a pilot course in humanities team-taught by three teachers, two from a senior high-school and one from a junior high-school, in Brookfield, Wisconsin. The specific subject matter is Greek and Roman culture. The curriculum is outlined and the basic reading list is included. (CLK)

  7. [Human monkeypox].

    PubMed

    Chastel, C

    2009-03-01

    Unlike other recent viral emergences, which were in majority caused by RNA viruses, the monkeypox results from infection by a DNA virus, an orthopoxvirus closely related to both vaccine and smallpox viruses and whose two genomic variants are known. Unexpectedly isolated from captive Asiatic monkeys and first considered as an laboratory curiosity, this virus was recognised in 1970 as an human pathogen in tropical Africa. Here it was responsible for sporadic cases following intrusions (for hunting) into tropical rain forests or rare outbreak with human-to-human transmission as observed in 1996 in Democratic Republic of Congo. As monkeypox in humans is not distinguishable from smallpox (a disease globally eradicated in 1977) it was only subjected to vigilant epidemiological surveillance and not considered as a potential threat outside Africa. This point of view radically changed in 2003 when monkeypox was introduced in the USA by African wild rodents and spread to 11 different states of this country. Responsible for 82 infections in American children and adults, this outbreak led to realize the sanitary hazards resulting from international trade of exotic animals and scientific investigations increasing extensively our knowledge of this zoonosis. PMID:18394820

  8. Humanizing Calculus

    ERIC Educational Resources Information Center

    Cirillo, Michelle

    2007-01-01

    In this article, the author explores the history and the mathematics used by Newton and Leibniz in their invention of calculus. The exploration of this topic is intended to show students that mathematics is a human invention. Suggestions are made to help teachers incorporate the mathematics and the history into their own lessons. (Contains 3…

  9. Human Rights in the Humanities

    ERIC Educational Resources Information Center

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  10. Human Protothecosis

    PubMed Central

    Lass-Flörl, Cornelia; Mayr, Astrid

    2007-01-01

    Human protothecosis is a rare infection caused by members of the genus Prototheca. Prototheca species are generally considered to be achlorophyllic algae and are ubiquitous in nature. The occurrence of protothecosis can be local or disseminated and acute or chronic, with the latter being more common. Diseases have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii) disseminated or systemic manifestations. Infections can occur in both immunocompetent and immunosuppressed patients, although more severe and disseminated infections tend to occur in immunocompromised individuals. Prototheca wickerhamii and Prototheca zopfii have been associated with human disease. Usually, treatment involves medical and surgical approaches; treatment failure is not uncommon. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date. Among them, amphotericin B displays the best activity against Prototheca spp. Diagnosis is largely made upon detection of characteristic structures observed on histopathologic examination of tissue. PMID:17428884

  11. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  12. Human evolution.

    PubMed

    Wood, B

    1996-12-01

    The common ancestor of modern humans and the great apes is estimated to have lived between 5 and 8 Myrs ago, but the earliest evidence in the human, or hominid, fossil record is Ardipithecus ramidus, from a 4.5 Myr Ethiopian site. This genus was succeeded by Australopithecus, within which four species are presently recognised. All combine a relatively primitive postcranial skeleton, a dentition with expanded chewing teeth and a small brain. The most primitive species in our own genus, Homo habilis and Homo rudolfensis, are little advanced over the australopithecines and with hindsight their inclusion in Homo may not be appropriate. The first species to share a substantial number of features with later Homo is Homo ergaster, or 'early African Homo erectus', which appears in the fossil record around 2.0 Myr. Outside Africa, fossil hominids appear as Homo erectus-like hominids, in mainland Asia and in Indonesia close to 2 Myr ago; the earliest good evidence of 'archaic Homo' in Europe is dated at between 600-700 Kyr before the present. Anatomically modern human, or Homo sapiens, fossils are seen first in the fossil record in Africa around 150 Kyr ago. Taken together with molecular evidence on the extent of DNA variation, this suggests that the transition from 'archaic' to 'modern' Homo may have taken place in Africa. PMID:8976151

  13. Human Capital, (Human) Capabilities and Higher Education

    ERIC Educational Resources Information Center

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  14. Human Heredity: Genetic Mechanisms in Humans.

    ERIC Educational Resources Information Center

    Blank, C. E.

    1988-01-01

    Discussed are some of the uncertainties in human genetic mechanisms that are often presented as dogma in Biology textbooks. Presented is a brief historical background and illustrations involving chromosome abnormality in humans and linkage studies in humans. (CW)

  15. Human schistosomiasis

    PubMed Central

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2015-01-01

    Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. PMID:24698483

  16. Human Astroviruses

    PubMed Central

    Pintó, Rosa M.; Guix, Susana

    2014-01-01

    SUMMARY Human astroviruses (HAtVs) are positive-sense single-stranded RNA viruses that were discovered in 1975. Astroviruses infecting other species, particularly mammalian and avian, were identified and classified into the genera Mamastrovirus and Avastrovirus. Through next-generation sequencing, many new astroviruses infecting different species, including humans, have been described, and the Astroviridae family shows a high diversity and zoonotic potential. Three divergent groups of HAstVs are recognized: the classic (MAstV 1), HAstV-MLB (MAstV 6), and HAstV-VA/HMO (MAstV 8 and MAstV 9) groups. Classic HAstVs contain 8 serotypes and account for 2 to 9% of all acute nonbacterial gastroenteritis in children worldwide. Infections are usually self-limiting but can also spread systemically and cause severe infections in immunocompromised patients. The other groups have also been identified in children with gastroenteritis, but extraintestinal pathologies have been suggested for them as well. Classic HAstVs may be grown in cells, allowing the study of their cell cycle, which is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future health threats. This review focuses on the basic virology, pathogenesis, host response, epidemiology, diagnostic assays, and prevention strategies for HAstVs. PMID:25278582

  17. Walker Prize Lecture, 1977. Choriocarcinoma: can we afford to cure cancer.

    PubMed Central

    Bagshawe, K. D.

    1978-01-01

    The way the management of patients with trophoblastic tumours has depended on the acquisition of new knowledge and new drugs is demonstrated. Emphasis is put on the ability to detect early disease by biochemical markers and on the ability to define on a multifactorial basis the resistance potential of the tumours. This provides a basis for stratification of treatment and the use of prophylactic chemotherapy to prevent cerebral metastases in certain patients. Although chemotherapy is often intensive and prolonged, there has so far been little evidence of long-term effects and many women have had normal pregnancies subsequently, but the limitations of present data are discussed. The difficulties of matching available resources to society's needs in the cancer field make it necessary to consider whether such treatment is unjustifiably expensive. It is shown that for these tumours early diagnosis not only proves effective in therapeutic terms but provides substantial financial savings. It is suggested that screening programmes for cancer cannot be accepted or rejected on principle. In judging them on their individual merits it is appropriate to anticipate interaction between earlier diagnosis and more effective drug treatment. PMID:626471

  18. The Diagnosis of Choriocarcinoma in Molar Pregnancies: A Revised Approach in Clinical Testing

    PubMed Central

    Duffy, Lisa; Zhang, Liangtao; Sheath, Karen; Love, Donald R.; George, Alice M.

    2015-01-01

    Background Hydatidiform moles occur in approximately 1 in 1,500 pregnancies; however, early miscarriages or spontaneous abortions may not be correctly identified as molar pregnancies due to poor differentiation of chorionic villi. Methods The current clinical testing algorithm used for the detection of hydatidiform moles uses a combination of morphological analysis and p57 immunostaining followed by ploidy testing to establish a diagnosis of either a complete or partial molar pregnancy. We review here 198 referrals for fluorescence in situ hybridization (FISH) ploidy testing, where the initial diagnosis based on morphology is compared to the final diagnosis based on a combination of morphology, FISH and p57 immunohistochemical (IHC) staining. Results Approximately 40% of cases were determined to be genetically abnormal, but only 28.8% of cases were diagnosed as molar pregnancies. The underestimation of complete molar pregnancies and those with androgenetic inheritance was also found to be likely using conventional diagnostic methods, as atypical p57 staining was observed in approximately 10% of cases. Conclusions Our findings suggest that a revised approach to testing products of conception is necessary, with cases screened according to their clinical history in order to distinguish molar pregnancy referrals from hydropic pregnancies. PMID:26566410

  19. Morphologic features of human chorionic gonadotropin- or alpha-fetoprotein-producing germ cell tumors of the central nervous system: histological heterogeneity and surgical meaning.

    PubMed

    Sugiyama, K; Arita, K; Tominaga, A; Hanaya, R; Taniguchi, E; Okamura, T; Itoh, Y; Yamasaki, F; Kurisu, K

    2001-01-01

    Our study of germ cell tumors (GCT) of the central nervous system (CNS) investigated the relationship between tumor histology and patient serum titers of human chorionic gonadotropin (HGC) and alpha-fetoprotein (AFP). Thirty-five patients were enrolled. Their serum titers of HCG (mlU/ml) and/or AFP (ng/ml) before initial treatment were available, as were tumor specimens obtained before the administration of adjuvant therapy. They were divided into three groups, depending on whether HCG alone (group H), AFP alone (group A), or both HCG and AFP (group HA) were detected. Each group was subdivided into three groups: patients in group I had H, A, and/or HA titers below 9.9; patients in group II/III had titers from 10.0 to 999; and those in group IV had titers of 1000 or more. Serial sections of tissue specimens were repeatedly stained, mainly with hematoxylin and eosin (H-E) stain, HCG immunostain, and AFP immunostain. There were seven patients in the H-I group and five in H-II/III. Of these 12 patients, 11 had germinomas (G) and one had an embryonal carcinoma (EC). Five patients were included in group A: one was classified as A-II/III and had a germinoma, and the remaining four patients were in A-IV and had yolk sac tumors (YST) or mixed GCT consisting mainly of YST or EC (MXGCT-YST, EC). The HA group consisted of 18 patients. Three were classified as HA-I and had germinomas; nine HA-II/III patients had T or MXGCT-T; and six HA-IV patients had choriocarcinoma (CC), YST, MXGCT-CC, or MXGCT-YST. Throughout the study, the situations for the elevated serum titers could be elucidated in only four cases (three in group A-IV and one in group HA-IV). These results led to the conclusion that serologic evaluation is superior to morphologic evaluation in diagnosing marker-producing GCTs. From a diagnostic perspective, the role of surgery is to verify the HCG- and AFP-immunonegative tissue in patients with G, T, and EC. PMID:11908867

  20. Differential expression of human chorionic gonadotropin (hCG) glycosylation isoforms in failing and continuing pregnancies: preliminary characterization of the hyperglycosylated hCG epitope.

    PubMed

    Kovalevskaya, G; Birken, S; Kakuma, T; Ozaki, N; Sauer, M; Lindheim, S; Cohen, M; Kelly, A; Schlatterer, J; O'Connor, J F

    2002-03-01

    Human chorionic gonadotropin (hCG) glycoforms change as pregnancy progresses. We have developed an antibody (B152) which can measure a hyperglycosylated early pregnancy isoform of hCG. This putative hyperglycosylated form of hCG arises very early in pregnancies and is rapidly replaced by an isoform that predominates for the remainder of the pregnancy. The profiles of these hCG glycoforms are measured as a ratio of values of two immunometric assays. The profiles of these ratios differ between pregnancies which persist and those which will experience early failure. In this report, daily urine hCG isoform ratios from donor eggs (no exogenous hCG pretreatment), in vitro fertilization pregnancies were profiled and analyzed from the first day following embryo transfer (ET). Significant differences were found between continuing pregnancy and pregnancy loss throughout days 5-20 post-ET. When hCG isoform ratios were analyzed from the first day of detectable hCG, pregnancy loss could be predicted in the case of a single fetus both during the 5- to 10-day time segment (P=0.018) and the 10- to 15-day time segment (P=0.045). When single and multiple fetus pregnancies were analyzed together significance was approached in the 10- to 15-day time period (P=0.058). In a second population of pregnant women who conceived naturally, in whom urine samples were collected at approximately weekly intervals to either term birth or clinical spontaneous abortion, the ratio could discriminate between miscarriages and normal term pregnancies (P=0.043). In later pregnancy, the ratio of hCG isoforms declined more rapidly in miscarriages than in term pregnancy. Antibody B152 was produced using a choriocarcinoma-derived hCG (C5), which was hyperglycosylated at both N- and O-linked sites and was 100% nicked at position beta(47-48). Western blot analyses supported the assay results showing that early pregnancy urine does not contain nicked C5-like hCG. Also, the early pregnancy hCG appeared to be the

  1. Human abilities.

    PubMed

    Sternberg, R J; Kaufman, J C

    1998-01-01

    This chapter reviews recent literature, primarily from the 1990s, on human abilities. The review opens with a consideration of the question of what intelligence is, and then considers some of the major definitions of intelligence, as well as implicit theories of intelligence around the world. Next, the chapter considers cognitive approaches to intelligence, and then biological approaches. It proceeds to psychometric or traditional approaches to intelligence, and then to broad, recent approaches. The different approaches raise somewhat different questions, and hence produce somewhat different answers. They have in common, however, the attempt to understand what kinds of mechanisms lead some people to adapt to, select, and shape environments in ways that match particularly well the demands of those environments. PMID:9496630

  2. The Digital Humanities as a Humanities Project

    ERIC Educational Resources Information Center

    Svensson, Patrik

    2012-01-01

    This article argues that the digital humanities can be seen as a humanities project in a time of significant change in the academy. The background is a number of scholarly, educational and technical challenges, the multiple epistemic traditions linked to the digital humanities, the potential reach of the field across and outside the humanities,…

  3. NATO Human View Architecture and Human Networks

    NASA Technical Reports Server (NTRS)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  4. Human oestrus

    PubMed Central

    Gangestad, Steven W; Thornhill, Randy

    2008-01-01

    For several decades, scholars of human sexuality have almost uniformly assumed that women evolutionarily lost oestrus—a phase of female sexuality occurring near ovulation and distinct from other phases of the ovarian cycle in terms of female sexual motivations and attractivity. In fact, we argue, this long-standing assumption is wrong. We review evidence that women's fertile-phase sexuality differs in a variety of ways from their sexuality during infertile phases of their cycles. In particular, when fertile in their cycles, women are particularly sexually attracted to a variety of features that likely are (or, ancestrally, were) indicators of genetic quality. As women's fertile-phase sexuality shares with other vertebrate females' fertile-phase sexuality a variety of functional and physiological features, we propose that the term oestrus appropriately applies to this phase in women. We discuss the function of women's non-fertile or extended sexuality and, based on empirical findings, suggest ways that fertile-phase sexuality in women has been shaped to partly function in the context of extra-pair mating. Men are particularly attracted to some features of fertile-phase women, but probably based on by-products of physiological changes males have been selected to detect, not because women signal their cycle-based fertility status. PMID:18252670

  5. Human Rhinoviruses

    PubMed Central

    Lamson, Daryl M.; St. George, Kirsten; Walsh, Thomas J.

    2013-01-01

    Human rhinoviruses (HRVs), first discovered in the 1950s, are responsible for more than one-half of cold-like illnesses and cost billions of dollars annually in medical visits and missed days of work. Advances in molecular methods have enhanced our understanding of the genomic structure of HRV and have led to the characterization of three genetically distinct HRV groups, designated groups A, B, and C, within the genus Enterovirus and the family Picornaviridae. HRVs are traditionally associated with upper respiratory tract infection, otitis media, and sinusitis. In recent years, the increasing implementation of PCR assays for respiratory virus detection in clinical laboratories has facilitated the recognition of HRV as a lower respiratory tract pathogen, particularly in patients with asthma, infants, elderly patients, and immunocompromised hosts. Cultured isolates of HRV remain important for studies of viral characteristics and disease pathogenesis. Indeed, whether the clinical manifestations of HRV are related directly to viral pathogenicity or secondary to the host immune response is the subject of ongoing research. There are currently no approved antiviral therapies for HRVs, and treatment remains primarily supportive. This review provides a comprehensive, up-to-date assessment of the basic virology, pathogenesis, clinical epidemiology, and laboratory features of and treatment and prevention strategies for HRVs. PMID:23297263

  6. Primary Gastric Chorioadenocarcinoma.

    PubMed

    Baraka, Bahaaeldin A; Al Kharusi, Suad S; Al Bahrani, Bassim J; Bhathagar, Gunmala

    2016-09-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

  7. Primary Gastric Chorioadenocarcinoma

    PubMed Central

    Baraka, Bahaaeldin A.; Al Kharusi, Suad S.; Al Bahrani, Bassim J.; Bhathagar, Gunmala

    2016-01-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

  8. p63 Inhibits Extravillous Trophoblast Migration and Maintains Cells in a Cytotrophoblast Stem Cell-Like State

    PubMed Central

    Li, Yingchun; Moretto-Zita, Matteo; Leon-Garcia, Sandra; Parast, Mana M.

    2015-01-01

    Proper differentiation of placental epithelial cells, called trophoblast, is required for implantation. Early during placentation, trophoblast cell columns help anchor the developing embryo in the uterine wall. Although proximally continuous with villous cytotrophoblast (CTB) distally, these cells differentiate into invasive extravillous trophoblast. We previously reported that p63, a p53 family member, is highly expressed in proliferative villous CTB and required for induction of the trophoblast lineage in human pluripotent stem cells. We now further explore its function in human trophoblast by using both primary CTB from the early placenta and established trophoblast cell lines. We show that p63 is expressed in epidermal growth factor receptor-positive CTB and that its expression decreases with differentiation into HLA-G+ extravillous trophoblast. In trophoblast cell lines, p63 is expressed in JEG3 cells but absent from HTR8 cells. Overexpression of p63 in both cell lines enhances cell proliferation and significantly reduces cell migration; conversely, down-regulation of p63 in JEG3 cells reduces cell proliferation and restores cell migration. Analysis of epithelial-to-mesenchymal transition, cell adhesion, and matrix degradation pathways shows that p63 blocks epithelial-to-mesenchymal transition, promotes a CTB-specific cell adhesion profile, and inhibits expression of matrix metalloproteinases. Taken together, these data show that p63 maintains the proliferative CTB state, at least partially through regulation of epithelial-to-mesenchymal transition, cell adhesion, and matrix degradation pathways. PMID:25307348

  9. [Human papillomaviruses].

    PubMed

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes. PMID:14610898

  10. Human Factors in Human-Systems Integration

    NASA Technical Reports Server (NTRS)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  11. Human Research Roadmap

    NASA Video Gallery

    Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and per...

  12. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  13. Human-machine interactions

    DOEpatents

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  14. Cooperation in human teaching.

    PubMed

    Kruger, Ann Cale

    2015-01-01

    Kline's evolutionary analysis of teaching provides welcome reframing for cross-species comparisons. However, theory based on competition cannot explain the transmission of human cultural elements that were collectively created. Humans evolved in a cultural niche and teaching-learning coevolved to transmit culture. To study human cultural variation in teaching, we need a more articulated theory of this distinctively human engagement. PMID:26786392

  15. Visualizing Humans by Computer.

    ERIC Educational Resources Information Center

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  16. Human Research Program Opportunities

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2014-01-01

    The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Human Research Program was designed to meet the needs of human space exploration, and understand and reduce the risk to crew health and performance in exploration missions.

  17. Humanism: A Christian Perspective.

    ERIC Educational Resources Information Center

    Kaasa, Harris; And Others

    As part of a four-college project to integrate the religious tradition with humanities teaching, humanism is discussed from a Christian perspective. Definitions of the terms humanism, religion, Christianity, and Christian humanism are provided. The latter is viewed as the issues surrounding the Christian approach to the dichotomy of good and evil…

  18. The Humanities: Interconnections.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1985-01-01

    Focusing on a wide range of interdisciplinary themes and ideas for humanities instruction, the 17 articles in this journal issue discuss the following topics: (1) literature, humanities, and the adult learner; (2) the role of the humanities in educating for a democracy; (3) humanities in the marketplace; (4) literature versus "great books" in high…

  19. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  20. Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation.

    PubMed

    Hyvönen, Mervi T; Ucal, Sebahat; Pasanen, Markku; Peräniemi, Sirpa; Weisell, Janne; Khomutov, Maxim; Khomutov, Alex R; Vepsäläinen, Jouko; Alhonen, Leena; Keinänen, Tuomo A

    2016-05-15

    Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) are associated with cancer. Triethylenetetramine (TETA) is a charge-deficient isosteric analogue of the polyamine spermidine (Spd) and a Cu(II)-chelating compound used for the treatment of Wilson's disease, and it has been implicated as a potential anticancer therapeutic drug. In the present study, we studied the effects of TETA in comparison with two other Cu(II)-chelators, D-penicillamine (PA) and tetrathiomolybdate (TTM), on polyamine metabolism in DU145 prostate carcinoma, MCF-7 breast carcinoma and JEG-3 choriocarcinoma cells. TETA induced antizyme, down-regulated ODC and inhibited [(14)C] Spd uptake. Moreover, it completely prevented α-difluoromethylornithine (DFMO)-induced increase in [(14)C] Spd uptake, and inhibited [(14)C] putrescine (Put) uptake and ODC activity in vivo Seven-day treatment of DU145 cells with TETA caused growth cessation by reducing intracellular polyamine levels and suppressing the formation of hypusinated eukaryotic translation initiation factor 5A (eIF5A). TETA or its N-acetylated metabolites also inhibited spermine (Spm), diamine and semicarbazide-sensitive amine oxidases and decreased the level of intracellular reactive oxygen species. Moreover, TETA inhibited the utilization of Put as energy source via the tricarboxylic acid (TCA) cycle, as indicated by decreased production of (14)CO2 from [(14)C] Put. These results indicate that TETA attacks multiple proven anticancer drug targets not attributed to copper chelation, which warrants further studies to reveal its potential in cancer chemoprevention and cure. PMID:27001865

  1. Boundaries of Humanities: Writing Medical Humanities

    ERIC Educational Resources Information Center

    Bolton, Gillie

    2008-01-01

    Literature and medicine is a discipline within medical humanities, which challenges medicine to reconfigure its scientific model to become interdisciplinary, and be disciplined by arts and humanities as well as science. The psychological, emotional, spiritual and physical are inextricably linked in people, inevitably entailing provisionality,…

  2. Virtual Human Project

    SciTech Connect

    Ward, RD

    2001-06-12

    This paper describes the development of a comprehensive human modeling environment, the Virtual Human, which will be used initially to model the human respiratory system for purposes of predicting pulmonary disease or injury using lung sounds. The details of the computational environment, including the development of a Virtual Human Thorax, a database for storing models, model parameters, and experimental data, and a Virtual Human web interface are outlined. Preliminary progress in developing this environment will be presented. A separate paper at the conference describes the modeling of sound generation using computational fluid dynamics and the modeling of sound propagation in the human respiratory system.

  3. Virtual Human project

    NASA Astrophysics Data System (ADS)

    Ward, Richard C.; Kruse, Kara L.; Allgood, Glenn O.; Hively, Lee M.; Fischer, K. N.; Munro, Nancy B.; Easterly, Clay E.

    2001-08-01

    This paper describes the development of a comprehensive human modeling environment, the Virtual Human, which will be used initially to model the human respiratory system for purposes of predicting pulmonary disease or injury using lung sounds. The details of the computational environment, including the development of a Virtual Human Thorax, a database for storing models, model parameters, and experimental data, and a Virtual Human web interface are outlined. Preliminary progress in developing this environment will be presented. A separate paper at the conference describes the modeling of sound generation using computational fluid dynamics and the modeling of sound propagation in the human respiratory system.

  4. Human bites (image)

    MedlinePlus

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  5. Telling the Human Story.

    ERIC Educational Resources Information Center

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  6. Human Resource Accounting System

    ERIC Educational Resources Information Center

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  7. Pathfinder: Humans in space

    NASA Technical Reports Server (NTRS)

    Anderson, John L.

    1988-01-01

    Viewgraphs are presented on the Pathfinder program. Information is given on human exploration of the solar system, technical requirements interfaces, program objectives, space suits, human performance, man-machine systems, space habitats, life support systems, and artificial gravity

  8. Human Rights Resource Catalogue.

    ERIC Educational Resources Information Center

    Zambrano, Elias, Comp.

    This document provides information about 25 programs/brochures which focus on human rights topics. Specific topics include: (1) counselor preparation; (2) multicultural awareness; (3) abuse and neglect; (4) Acquired Immune Deficiency Syndrome; (5) self-awareness; (6) human rights awareness and human rights of students; (7) cultural diversity; (8)…

  9. Production Of Human Antibodies

    NASA Technical Reports Server (NTRS)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  10. Whose Human Rights?

    ERIC Educational Resources Information Center

    Rendel, Margherita

    During the last 50 years, principles, institutions, and policies of human rights have been developed worldwide. This book brings together European and international conventions on human rights, the rights of women, and the users and uses of education, and places them in their wider context. It examines issues in how human rights work, the ways in…

  11. HUMAN USE INDEX (FUTURE)

    EPA Science Inventory

    Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the percentage of human land use in an area, including agriculture, urban and suburban development, and mining. Low values ...

  12. HUMAN USE INDEX

    EPA Science Inventory

    Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the percentage of human land use in an area, including agriculture, urban and suburban development, and mining. Low values ...

  13. Visible Human Project

    MedlinePlus

    ... Mobile Gallery Site Navigation Home The Visible Human Project ® Overview The Visible Human Project ® is an outgrowth of the NLM's 1986 Long- ... The long-term goal of the Visible Human Project ® is to produce a system of knowledge structures ...

  14. Human Rights Educational Resources.

    ERIC Educational Resources Information Center

    Flowers, Nancy

    1998-01-01

    Gives a variety of educational resources on human rights that include videos, resource notebooks, books, publications, and websites along with short descriptions of the materials. Provides the contact information for a list of human-rights organizations, such as the Center for Human Rights Education and the Franklin and Eleanor Roosevelt…

  15. Expanding Human Intelligence.

    ERIC Educational Resources Information Center

    Galyean, Beverly-Colleene

    1983-01-01

    The human brain is capable of mastering skills far beyond those it is now used for. Three questions about the further evolution of human intelligence are raised: What will be the next step in human intelligence? How is the next step manifesting itself? How can we prepare for those changes? (IS)

  16. Financing Human Capital.

    ERIC Educational Resources Information Center

    Juffras, Jason; Sawhill, Isabel V.

    This paper examines the government's role in financing human capital investments. It first examines why private investments in education, training, and other forms of human capital are likely to fall short of socially desirable levels. It then reviews past trends in public support for human resource investments. Finally, it discusses current…

  17. HUMAN EXPOSURE ACTIVITY PATTERNS

    EPA Science Inventory

    Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

  18. Has Human Evolution Stopped?

    PubMed Central

    Templeton, Alan R.

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences. PMID:23908778

  19. Some Criteria for Humanizing.

    ERIC Educational Resources Information Center

    Read, Charlotte S.

    Patterns for humanizing the information sciences include recognizing essential "humanness," taking a holistic approach to the subject field, and being aware of the epistemological nature of how people communicate and relate to others and themselves. The complete inclusion of the human factor in information theory researches can only amplify the…

  20. Esprit: A Humanities Magazine.

    ERIC Educational Resources Information Center

    Parker, Donald G.; Capella, Barry John

    In March 1984, the first issue of "Esprit," a semi-annual humanities magazine for the 56 two-year colleges in New York State, was published. The magazine seeks to confront the apparent decline of student interest in the humanities, community doubts about the relevance of the humanities, and the seeming indifference to the special truths inherent…

  1. Humanism in emergency medicine.

    PubMed

    Rosenzweig, S

    1993-09-01

    Emergency medicine has not yet appropriated "humanism" as a term of its own. Medical humanism needs to be interpreted in a way that is consistent with the practical goals of emergency medicine. In this essay, humanism in emergency medicine is defined by identifying the dehumanizing aspects of sudden illness and exploring of ways for sustaining the humanity of emergency department patients. Excerpts from Dr Oliver Sacks' autobiographical work A Leg to Stand On give voice to the human needs created by sudden illness and its treatment. PMID:8363690

  2. Human Mitochondrial Protein Database

    National Institute of Standards and Technology Data Gateway

    SRD 131 Human Mitochondrial Protein Database (Web, free access)   The Human Mitochondrial Protein Database (HMPDb) provides comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function. This database consolidates information from SwissProt, LocusLink, Protein Data Bank (PDB), GenBank, Genome Database (GDB), Online Mendelian Inheritance in Man (OMIM), Human Mitochondrial Genome Database (mtDB), MITOMAP, Neuromuscular Disease Center and Human 2-D PAGE Databases. This database is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases.

  3. Human-technology Integration

    NASA Astrophysics Data System (ADS)

    Mullen, Katharine M.

    Human-technology integration is the replacement of human parts and extension of human capabilities with engineered devices and substrates. Its result is hybrid biological-artificial systems. We discuss here four categories of products furthering human-technology integration: wearable computers, pervasive computing environments, engineered tissues and organs, and prosthetics, and introduce examples of currently realized systems in each category. We then note that realization of a completely artificial sytem via the path of human-technology integration presents the prospect of empirical confirmation of an aware artificially embodied system.

  4. Biological Races in Humans

    PubMed Central

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two most commonly used biological concepts of race, chimpanzees are indeed subdivided into races but humans are not. Adaptive traits, such as skin color, have frequently been used to define races in humans, but such adaptive traits reflect the underlying environmental factor to which they are adaptive and not overall genetic differentiation, and different adaptive traits define discordant groups. There are no objective criteria for choosing one adaptive trait over another to define race. As a consequence, adaptive traits do not define races in humans. Much of the recent scientific literature on human evolution portrays human populations as separate branches on an evolutionary tree. A tree-like structure among humans has been falsified whenever tested, so this practice is scientifically indefensible. It is also socially irresponsible as these pictorial representations of human evolution have more impact on the general public than nuanced phrases in the text of a scientific paper. Humans have much genetic diversity, but the vast majority of this diversity reflects individual uniqueness and not race. PMID:23684745

  5. Biological races in humans.

    PubMed

    Templeton, Alan R

    2013-09-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two most commonly used biological concepts of race, chimpanzees are indeed subdivided into races but humans are not. Adaptive traits, such as skin color, have frequently been used to define races in humans, but such adaptive traits reflect the underlying environmental factor to which they are adaptive and not overall genetic differentiation, and different adaptive traits define discordant groups. There are no objective criteria for choosing one adaptive trait over another to define race. As a consequence, adaptive traits do not define races in humans. Much of the recent scientific literature on human evolution portrays human populations as separate branches on an evolutionary tree. A tree-like structure among humans has been falsified whenever tested, so this practice is scientifically indefensible. It is also socially irresponsible as these pictorial representations of human evolution have more impact on the general public than nuanced phrases in the text of a scientific paper. Humans have much genetic diversity, but the vast majority of this diversity reflects individual uniqueness and not race. PMID:23684745

  6. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  7. Human research subjects as human research workers.

    PubMed

    Lynch, Holly Fernandez

    2014-01-01

    Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly. PMID:25051653

  8. Integrated Environmental Modelling: human decisions, human challenges

    USGS Publications Warehouse

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  9. Human organ markets and inherent human dignity.

    PubMed

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept. PMID:24979876

  10. Human Performance in Space

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  11. Human reliability analysis

    SciTech Connect

    Dougherty, E.M.; Fragola, J.R.

    1988-01-01

    The authors present a treatment of human reliability analysis incorporating an introduction to probabilistic risk assessment for nuclear power generating stations. They treat the subject according to the framework established for general systems theory. Draws upon reliability analysis, psychology, human factors engineering, and statistics, integrating elements of these fields within a systems framework. Provides a history of human reliability analysis, and includes examples of the application of the systems approach.

  12. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

    Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

    2012-06-01

    The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

  13. Artificial human vision camera

    NASA Astrophysics Data System (ADS)

    Goudou, J.-F.; Maggio, S.; Fagno, M.

    2014-10-01

    In this paper we present a real-time vision system modeling the human vision system. Our purpose is to inspire from human vision bio-mechanics to improve robotic capabilities for tasks such as objects detection and tracking. This work describes first the bio-mechanical discrepancies between human vision and classic cameras and the retinal processing stage that takes place in the eye, before the optic nerve. The second part describes our implementation of these principles on a 3-camera optical, mechanical and software model of the human eyes and associated bio-inspired attention model.

  14. The psychology of humanness.

    PubMed

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures. PMID:23947277

  15. Robotics for Human Exploration

    NASA Technical Reports Server (NTRS)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  16. Health and Humanity: Humanities 401 Syllabus.

    ERIC Educational Resources Information Center

    Snowden, Fraser; Taylor, Maxine

    A syllabus for the "Health and Humanities" interdisciplinary course at Northwestern State University, Louisiana, is presented. An introduction suggests that with the proliferation of technological advances in the field of health care, there is a need for reconsideration of many moral, ethical, legal, and humanistic questions. Information is…

  17. Developing Human Resources through Actualizing Human Potential

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  18. Human Simulated Diving Experiments.

    ERIC Educational Resources Information Center

    Bruce, David S.; Speck, Dexter F.

    1979-01-01

    This report details several simulated divinq experiments on the human. These are suitable for undergraduate or graduate laboratories in human or environmental physiology. The experiment demonstrates that a diving reflex is precipitated by both facial cooling and apnea. (Author/RE)

  19. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  20. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  1. Evaluating the Humanities

    ERIC Educational Resources Information Center

    Brody, Howard

    2013-01-01

    How can one measure the value of teaching the humanities? The problem of assessment and accountability is prominent today, of course, in secondary and higher education. It is perhaps even more acute for those who teach the humanities in nontraditional settings, such as medical and other professional schools. The public assumes that academes can…

  2. Environment and the Humanities.

    ERIC Educational Resources Information Center

    Allen, Rodney F., Ed.; And Others

    As a conference report, the booklet is primarily devoted to abstracts of papers presented at a Conference on Environment and Humanities held in Tallahassee, Florida, April 25-27, 1976. Dr. Huston Smith of Syracuse University, the main speaker, addressed the issue of "Humanities and Environmental Awareness." Other topics discussed included: (1)…

  3. Teaching Human Rights Law.

    ERIC Educational Resources Information Center

    Berman, Howard R.

    1985-01-01

    The international community has developed a system of human rights law relevant to many areas of legal encounter, which American law schools have been slow to incorporate into curricula. Teaching human rights law provides an opportunity for law schools to enrich the learning process and contribute creatively to the respect for rights in society.…

  4. Human Pythiosis, Brazil

    PubMed Central

    Bosco, Sandra de Moraes Gimenes; Araújo, João Pessoa; Candeias, João Manuel Grisi; Fabiano de Franco, Marcello; Marques, Mariangela Esther Alencar; Mendoza, Leonel; Pires de Camargo, Rosangela; Marques, Silvio Alencar

    2005-01-01

    Pythiosis, caused by Pythium insidiosum, occurs in humans and animals and is acquired from aquatic environments that harbor the emerging pathogen. Diagnosis is difficult because clinical and histopathologic features are not pathognomonic. We report the first human case of pythiosis from Brazil, diagnosed by using culture and rDNA sequencing. PMID:15890126

  5. Human Mind Maps

    ERIC Educational Resources Information Center

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  6. Human Powered Centrifuge

    NASA Technical Reports Server (NTRS)

    Mulenburg, Gerald M. (Inventor); Vernikos, Joan (Inventor)

    1997-01-01

    A human powered centrifuge has independently established turntable angular velocity and human power input. A control system allows excess input power to be stored as electric energy in a battery or dissipated as heat through a resistors. In a mechanical embodiment, the excess power is dissipated in a friction brake.

  7. Human Sociobiology: Wilson's Fallacy.

    ERIC Educational Resources Information Center

    Lehrman, Nathaniel S.

    1981-01-01

    Presents an introduction to and a critique of E.O. Wilson's new science of sociobiology, which focuses on explaining the social behavior of species as diverse as ants, apes, and humans. Suggests that Wilson has gone beyond his data in claiming that complex human behaviors such as altruism are caused to any extent by genetic, as opposed to…

  8. Manage "Human Capital" Strategically

    ERIC Educational Resources Information Center

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  9. Quantification of human responses

    NASA Technical Reports Server (NTRS)

    Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

    1992-01-01

    Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

  10. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

    The Human Exposure Research Branch has developed several enzyme-linked immunosorbent assay (ELISA) methods to support human exposure assessment studies. Immunoassays to detect low levels (<10 ng/mL) of chlorpyrifos in food, track-in dirt and house dust have been applied to sam...

  11. Humane Education Projects Handbook.

    ERIC Educational Resources Information Center

    Junior League of Ogden, UT.

    This handbook was developed to promote interest in humane education and to encourage the adoption of humane education projects. Although specifically designed to assist Junior Leagues in developing such projects, the content should prove valuable to animal welfare organizations, zoos, aquariums, nature centers, and other project-oriented groups…

  12. Methods in human cytogenetics

    SciTech Connect

    1993-12-31

    Chapter 4, discusses the various techniques used in the study human cytogenetics. The methods are discussed in historical order, from direct methods to tissue culture techniques, prenatal studies, meiotic studies, sex chromatin techniques, banding techniques, prophase banding and replication studies. Nomenclature of human chromosomes and quantitative methods are also mentioned. 60 refs., 3 figs.

  13. HSI in Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Baggerman, Susan D.

    2007-01-01

    This viewgraph document examines the scope of Human Systems Integration (HSI) at NASA, and the implementation of HSI in the human space flight programs. Two areas of interest are the Responsibilities and the lessons learned from the International Space Station and the strategy and approach for the Crew Exploration Vehicle.

  14. Human Granulocytic Anaplasmosis, Japan

    PubMed Central

    Gaowa; Wuritu; Kawamori, Fumihiko; Wu, Dongxing; Yoshikawa, Yuko; Chiya, Seizou; Fukunaga, Kazutoshi; Funato, Toyohiko; Shiojiri, Masaaki; Nakajima, Hideki; Hamauzu, Yoshiji; Takano, Ai; Kawabata, Hiroki; Ando, Shuji; Kishimoto, Toshio

    2013-01-01

    We retrospectively confirmed 2 cases of human Anaplasma phagocytophilum infection. Patient blood samples contained unique p44/msp2 for the pathogen, and antibodies bound to A. phagocytophilum antigens propagated in THP-1 rather than HL60 cells. Unless both cell lines are used for serodiagnosis of rickettsiosis-like infections, cases of human granulocytic anaplasmosis could go undetected. PMID:23460988

  15. Neurobehavioral testing in humans.

    PubMed

    Anger, W K; Rohlman, D S; Storzbach, D

    2001-05-01

    The evaluation of the effects of chemical exposures on humans is a worldwide concern, and most chemicals have not been evaluated for neurotoxic effect. Human neurobehavioral research or clinical evaluations of populations exposed to chemicals must be carefully planned and structured. This unit describes the steps required to create such a study, select the appropriate measures, and evaluate the results. PMID:20957644

  16. Humanism within Globalization

    ERIC Educational Resources Information Center

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  17. The Humanities' Value

    ERIC Educational Resources Information Center

    Harpham, Geoffrey Galt

    2009-01-01

    Why should society support the humanities when so many people are suffering from the effects of the economic crisis? What claim do the humanities, or scholarship generally, have on increasingly limited resources? Shouldn't such pursuits be considered luxuries at a time when people should be focusing on essentials? The alleviation of human…

  18. Human Space Flight

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Mount, Frances

    2004-01-01

    The first human space flight, in the early 1960s, was aimed primarily at determining whether humans could indeed survive and function in micro-gravity. Would eating and sleeping be possible? What mental and physical tasks could be performed? Subsequent programs increased the complexity of the tasks the crew performed. Table 1 summarizes the history of U.S. space flight, showing the projects, their dates, crew sizes, and mission durations. With over forty years of experience with human space flight, the emphasis now is on how to design space vehicles, habitats, and missions to produce the greatest returns to human knowledge. What are the roles of the humans in space flight in low earth orbit, on the moon, and in exploring Mars?

  19. Mars Human Exploration Objectives

    NASA Technical Reports Server (NTRS)

    Briggs, Geoff

    1998-01-01

    This paper reviews the objectives and other considerations of Human exploration of Mars. The objectives of human exploration of Mars are: (1) to learn how Mars is similar to, and different from, Earth; (2) to explore possible life, past and present; (3) to discover what Mars is like now from the perspective of Geoscience and geologic history; and (4) how did Mars form and how did its formation differ from Earth. Considerations of human Martian exploration involve: (1) having a capable base laboratory; (2) having long range transportation; (3) having operational autonomy of the crew, and the requirement of the crew to possess a range of new cognitive processes along with easy communications with terrestrial colleagues; and finally (4) creating the human habitat along with human factors which involve more than just survivability.

  20. Humanization of immunotoxins.

    PubMed

    Rybak, S M; Hoogenboom, H R; Meade, H M; Raus, J C; Schwartz, D; Youle, R J

    1992-04-15

    The construction and expression of a chimeric gene encoding a mouse/human antibody to the human transferrin receptor fused to the gene for angiogenin, a human homolog of pancreatic RNase, are described. F(ab')2-like antibody-enzyme fusions were prepared by linking the gene for human angiogenin to a chimeric anti-transferrin receptor heavy chain gene. The antibody-enzyme fusion gene was introduced into a transfectoma that secretes the chimeric light chain of the same antibody, and cell lines were cloned that synthesize and secrete the antibody-enzyme fusion protein of the expected size at a concentration of 1-5 ng/ml. Culture supernatants from clones secreting the fusion protein caused inhibition of growth and protein synthesis of K562 cells that express the human transferrin receptor but not toward a non-human-derived cell line that lacks this receptor. Whereas excess antibody to the same receptor did not itself inhibit protein synthesis, it was able to completely prevent the protein synthesis inhibition caused by the fusion protein. These results indicate that the cytotoxicity is due to a transferrin receptor-mediated mechanism involving the angiogenin portion of the fusion protein and demonstrate the feasibility of constructing recombinant antibody-RNase molecules capable of killing tumor cells bearing the transferrin receptor. The significance of the acquired cytotoxicity of a mouse/human chimeric antibody linked to a human protein may bear importantly in human therapeutic strategies that use mouse antibodies linked to toxins from plants or bacteria to target tumor cells. It is expected that the humanization of immunotoxins will lead to less toxicity and immunogenicity than currently available reagents. PMID:1565609

  1. Novel human astroviruses: Novel human diseases?

    PubMed

    Vu, Diem-Lan; Cordey, Samuel; Brito, Francisco; Kaiser, Laurent

    2016-09-01

    Astroviruses are small, non-enveloped, single-stranded positive RNA viruses that belong to the Astroviridae family. While classical human astroviruses (HAstV) are a well-recognized cause of acute non-bacterial diarrhea among young children worldwide, novel astroviruses, named HAstV-MLB and HAstV-VA/HMO, have been identified recently in humans by molecular assays. They are phylogenetically more related to animal astroviruses than to classical human astroviruses, thus suggesting cross-species transmission. Serological studies demonstrated a surprisingly high seroprevalence in certain populations and highlighted a high infection rate in the early years of life. Although their pathogenic role has not yet been clearly determined, novel astrovirus RNA sequences have been identified in different biological specimens of symptomatic patients, including the feces, plasma, cerebrospinal fluid, and brain biopsies. Thus, there is evidence that they could contribute not only to digestive tract infection, but also to unexpected clinical syndromes, notably encephalitis and meningitis. Severe infections affect mainly immunocompromised patients. These findings indicate that novel astroviruses should be considered in the differential diagnosis of immunocompromised patients with meningitis or encephalitis of unknown origin. PMID:27434149

  2. Archaea on human skin.

    PubMed

    Probst, Alexander J; Auerbach, Anna K; Moissl-Eichinger, Christine

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin. PMID:23776475

  3. Human Space Exploration

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Antony

    2014-01-01

    The Mars probe, launched by India a few months ago, is on its way to Mars. At this juncture, it is appropriate to talk about the opportunities presented to us for the Human Exploration of Mars. I am planning to highlight some of the challenges to take humans to Mars, descend, land, stay, ascend and return home safely. The logistics of carrying the necessary accessories to stay at Mars will be delivered in multiple stages using robotic missions. The primary ingredients for human survival is air, water, food and shelter and the necessity to recycle the primary ingredients will be articulated. Humans have to travel beyond the van Allen radiation belt under microgravity condition during this inter-planetary travel for about 6 months minimum one way. The deconditioning of human system under microgravity conditions and protection of humans from Galactic cosmic radiation during the travel should be taken into consideration. The multi-disciplinary effort to keep the humans safe and functional during this journey will be addressed.

  4. Managing human bites

    PubMed Central

    Patil, Pradnya D; Panchabhai, Tanmay S; Galwankar, Sagar C

    2009-01-01

    Human bites are frequently overlooked in making a diagnosis in the emergency room. They are particularly notorious due to the polymicrobial nature of human saliva inoculated in the wound and the risk they pose for transmission of infectious diseases. Early treatment, appropriate prophylaxis and surgical evaluation are the key to achieving desired treatment outcomes. Through this article, we have tried to summarize the diagnostic features, complications as well as the recommended treatment alternatives for human bites based on the current available evidence. PMID:20009309

  5. Human Genome Project

    SciTech Connect

    Block, S.; Cornwall, J.; Dally, W.; Dyson, F.; Fortson, N.; Joyce, G.; Kimble, H. J.; Lewis, N.; Max, C.; Prince, T.; Schwitters, R.; Weinberger, P.; Woodin, W. H.

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  6. Human Photoreactivating Enzyme

    PubMed Central

    Sutherland, J. C.; Sutherland, B. M.

    1975-01-01

    The action spectrum for photoreactivation by enzymes from human leukocytes and fibroblasts extends from 300 to approximately 600 nm with a maximum near 400 nm. The ability of the human enzymes to utilize light of wavelengths greater than 500 nm suggested that yellow or gold lights conventionally used as safelights for photoreactivation might serve as sources of photoreactivating light for these enzymes. Experiments using lights with a range of spectral outputs confirm that the standard yellow “safe” lights do produce photoreactivation by the human but not the Escherichia coli enzyme. PMID:19211015

  7. Human Computer Interaction

    NASA Astrophysics Data System (ADS)

    Bhagwani, Akhilesh; Sengar, Chitransh; Talwaniper, Jyotsna; Sharma, Shaan

    2012-08-01

    The paper basically deals with the study of HCI (Human computer interaction) or BCI(Brain-Computer-Interfaces) Technology that can be used for capturing brain signals and translating them into commands that allow humans to control (just by thinking) devices such as computers, robots, rehabilitation technology and virtual reality environments. The HCI is based as a direct communication pathway between the brain and an external device. BCIs are often aimed at assisting, augmenting, or repairing human cognitive or sensory-motor functions.The paper also deals with many advantages of BCI Technology along with some of its applications and some major drawbacks.

  8. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes. PMID:26395141

  9. The human genome project

    SciTech Connect

    Bell, G.I.

    1991-06-01

    The Human Genome Project will obtain high-resolution genetic and physical maps of each human chromosome and, somewhat later, of the complete nucleotide sequence of the deoxyribonucleic acid (DNA) in a human cell. The talk will begin with an extended introduction to explain the Project to nonbiologists and to show that map construction and sequence determination require extensive computation in order to determine the correct order of the mapped entities and to provide estimates of uncertainty. Computational analysis of the sequence data will become an increasingly important part of the project, and some computational challenges are described. 5 refs.

  10. The Concept of Being Human.

    ERIC Educational Resources Information Center

    Purcell, Royal

    This analysis of the relationship between humanism and humanitarianism outlines educational goals that should lead to a more humane world. Section 1, an outline of human life examines six substructures--human life, individuality, amenity, contact, actualization, and problems. A definition and examples of humanism in section 2 are elaborated into a…

  11. Creativity: The Human Resource.

    ERIC Educational Resources Information Center

    Lewis, Richard W.

    1979-01-01

    The author discusses an exhibition entitled "Creativity--The Human Resource." The exhibition examines the work of 15 Americans, such as designer Buckminster Fuller and artist Judy Chicago, who have contributed in special ways to the arts and sciences. (PHR)

  12. Pesticides and Human Health

    MedlinePlus

    ... Control a pest Integrated Pest Management What are pesticides? Herbicides Disinfectants Fungicides Insecticides Natural and Biological Pesticides ... Rodenticides Other types of pesticides Disponible en español Pesticides and Human Health Pesticides have a specific purpose ...

  13. Teaching about Human Geography.

    ERIC Educational Resources Information Center

    Schlene, Vickie J.

    1991-01-01

    Presents a sampling of items from the ERIC database concerning the teaching of human geography. Includes documents dealing with Africa, Asia, the United States, Canada, Antarctica, and geographic concepts. Explains how to obtain ERIC documents. (SG)

  14. Approaches to Human Communication.

    ERIC Educational Resources Information Center

    Budd, Richard W., Ed.; Ruben, Brent D., Ed.

    This anthology of essays approaches human communication from the points of view of: anthropology, art biology, economics, encounter groups, semantics, general system theory, history, information theory, international behavior, journalism, linguistics, mass media, neurophysiology, nonverbal behavior, organizational behavior, philosophy, political…

  15. HPV (Human Papillomavirus)

    MedlinePlus

    ... Health Topics Mammography Women and Diabetes HPV, HIV, Birth Control Heart Health for Women Pregnancy Menopause More Women's Health Topics Resources for You Human Papillomavirus Vaccine HPV Information in Other Languages Women ...

  16. Statement on Human Cloning

    MedlinePlus

    ... form Search American Association for the Advancement of Science Statement on Human Cloning Print Email Tweet The American Association for the Advancement of Science (AAAS) recognizes the intense debates within our society ...

  17. Human Reliability Program Overview

    SciTech Connect

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  18. Sociobiology and Humanism.

    ERIC Educational Resources Information Center

    Hoult, Thomas Ford

    1979-01-01

    Describes the fundamental conflict between the implications of sociobiology and the aspirations of humanists. Sociobiology tends to rationalize and defend special privileges for the powerful few, while humanism stresses equality of opportunity. Journal availability: see SO 507 272. (Author)

  19. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  20. Human Biomass Consumption

    NASA Video Gallery

    Humans are using an increasing amount of Earth’s annual production of plants. Research shows that, from 1995 to 2005, consumption rose from 20 to 25 percent of the planet's annual production. Wha...

  1. Human Resource Planning

    ERIC Educational Resources Information Center

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  2. The Human Hazard.

    ERIC Educational Resources Information Center

    Tickell, Crispin

    1995-01-01

    Examines the plight of environmental refugees and the adequacy of political responses to the situation. Discusses the consequences of accelerated environmental change, particularly the impact of global warming on human migration. (LZ)

  3. Human Systems Integration Introduction

    NASA Video Gallery

    This lecture provides an overview of Human Systems Integration (HSI), its implementation cost and return on investment, HSI domains, how HSI fits into the NASA organization structure, HSI roles and...

  4. Human Computers 1947

    NASA Technical Reports Server (NTRS)

    1947-01-01

    Langley's human computers at work in 1947. The female presence at Langley, who performed mathematical computations for male staff. Photograph published in Winds of Change, 75th Anniversary NASA publication (page 48), by James Schultz.

  5. Habitability and Human Factors Contributions to Human Space Flight

    NASA Technical Reports Server (NTRS)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  6. Human Assisted Assembly Processes

    SciTech Connect

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  7. Pushing Human Frontiers

    NASA Technical Reports Server (NTRS)

    Zubrin, Robert

    2005-01-01

    With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

  8. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1990-01-01

    This paper describes several case studies of human space exploration, considered by the NASA's Office of Exploration in 1988. Special attention is given to the mission scenarios, the critical technology required in these expeditions, and the extraterrestrial power requirements of significant system elements. The cases examined include a manned expedition to Phobos, the inner Martian moon; a human expedition to Mars; the Lunar Observatory; and a lunar outpost to early Mars evolution.

  9. The human oncogenic viruses

    SciTech Connect

    Luderer, A.A.; Weetall, H.H

    1986-01-01

    This book contains eight selections. The titles are: Cytogenetics of the Leukemias and Lymphomas; Cytogenetics of Solid Tumors: Renal Cell Carcinoma, Malignant Melanoma, Retinoblastoma, and Wilms' Tumor; Elucidation of a Normal Function for a Human Proto-Oncogene; Detection of HSV-2 Genes and Gene Products in Cervical Neoplasia; Papillomaviruses in Anogennital Neoplasms; Human Epstein-Barr Virus and Cancer; Hepatitis B Virus and Hepatocellular Carcinoma; and Kaposi's Sarcoma: Acquired Immunodeficiency Syndrome (AIDS) and Associated Viruses.

  10. Humans in space.

    PubMed

    White, R J; Averner, M

    2001-02-22

    Many successful space missions over the past 40 years have highlighted the advantages and necessity of humans in the exploration of space. But as space travel becomes ever more feasible in the twenty-first century, the health and safety of future space explorers will be paramount. In particular, understanding the risks posed by exposure to radiation and extended weightlessness will be crucial if humans are to travel far from Earth. PMID:11234026

  11. Mapping the human genome

    SciTech Connect

    Annas, G.C.; Elias, S.

    1992-01-01

    This article is a review of the book Mapping the Human Genome: Using Law and Ethics as Guides, edited by George C. Annas and Sherman Elias. The book is a collection of essays on the subject of using ethics and laws as guides to justify human gene mapping. It addresses specific issues such problems related to eugenics, patents, insurance as well as broad issues such as the societal definitions of normality.

  12. Meeting human needs

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  13. Human ocular anatomy.

    PubMed

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes. PMID:25704934

  14. Evolution and human sexuality.

    PubMed

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory. PMID:24151100

  15. Human immunoglobulin allotypes

    PubMed Central

    Lefranc, Marie-Paule

    2009-01-01

    More than twenty recombinant monoclonal antibodies are approved as therapeutics. Almost all of these are based on the whole IgG isotype format, but vary in the origin of the variable regions between mouse (chimeric), humanized mouse and fully human sequences; all of those with whole IgG format employ human constant region sequences. Currently, the opposing merits of the four IgG subclasses are considered with respect to the in vivo biological activities considered to be appropriate to the disease indication being treated. Human heavy chain genes also exhibit extensive structural polymorphism(s) and, being closely linked, are inherited as a haplotype. Polymorphisms (allotypes) within the IgG isotype were originally discovered and described using serological reagents derived from humans; demonstrating that allotypic variants can be immunogenic and provoke antibody responses as a result of allo-immunization. The serologically defined allotypes differ widely within and between population groups; therefore, a mAb of a given allotype will, inevitably, be delivered to a cohort of patients homozygous for the alternative allotype. This publication reviews the serologically defined human IgG allotypes and considers the potential for allotype differences to contribute to or potentiate immunogenicity. PMID:20073133

  16. The human telomere

    SciTech Connect

    Moyzis, R.K.

    1989-01-01

    An ultimate goal of human genetics is the generation of a complete physical and ''functional'' map of the human genome. Twenty-five percent of human DNA, however, consists of repetitive DNA sequences. These repetitive DNA sequences are thought to arise by many mechanisms, from direct sequence amplification by the unequal recombination of homologous DNA regions to the reverse flow of genetic information. A general outline of the chromosomal organization of these repetitive sequences will be discussed. Our working hypothesis is that certain classes of human repetitive DNA sequences ''encode'' the information necessary for defining long-range genomic structure. Evidence will be presented that the first goal of this research, the identification and cloning of the human telomere, has been achieved. A human repetitive DNA library was constructed from randomly sheared, reassociated, and oligo(G/center dot/C)-tailed DNA, a method that minimizes the potential loss of sequences devoid of a given restriction enzyme site. Sequences too large to clone efficiently in cosmid or /lambda/ vectors, such as centromeric repeats, or telomeric sequences with an end incompatible for cloning, should be present in this library. In order to isolate highly conserved repetitive DNA sequences, this library was screened with radiolabeled hamster Cot50 repetitive DNA. Two clones, containing tandem arrays of the sequence (TTAGGG), were isolated by this method. 30 refs., 1 fig., 2 tabs.

  17. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  18. Human bites - self-care

    MedlinePlus

    Bites - human - self-care ... Human bites can occur in two ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  19. Human behavior and human performance: Psychomotor demands

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The results of several experiments are presented in abstract form. These studies are critical for the interpretation and acceptance of flight based science to be conducted by the Behavior and Performance project. Some representative titles are as follow: External audio for IBM/PC compatible computers; A comparative assessment of psychomotor performance (target prediction by humans and macaques); Response path (a dependent measure for computer maze solving and other tasks); Behavioral asymmetries of psychomotor performance in Rhesus monkey (a dissociation between hand preference and skill); Testing primates with joystick based automated apparatus; and Environmental enrichment and performance assessment for ground or flight based research with primates;

  20. Developing Human Performance Measures

    SciTech Connect

    Jeffrey Joe; Bruce Hallbert; Larry Blackwood; Donald Dudehoeffer; Kent Hansen

    2006-05-01

    Through the reactor oversight process (ROP), the U.S. Nuclear Regulatory Commission (NRC) monitors the performance of utilities licensed to operate nuclear power plants. The process is designed to assure public health and safety by providing reasonable assurance that licensees are meeting the cornerstones of safety and designated crosscutting elements. The reactor inspection program, together with performance indicators (PIs), and enforcement activities form the basis for the NRC’s risk-informed, performance based regulatory framework. While human performance is a key component in the safe operation of nuclear power plants and is a designated cross-cutting element of the ROP, there is currently no direct inspection or performance indicator for assessing human performance. Rather, when human performance is identified as a substantive cross cutting element in any 1 of 3 categories (resources, organizational or personnel), it is then evaluated for common themes to determine if follow-up actions are warranted. However, variability in human performance occurs from day to day, across activities that vary in complexity, and workgroups, contributing to the uncertainty in the outcomes of performance. While some variability in human performance may be random, much of the variability may be attributed to factors that are not currently assessed. There is a need to identify and assess aspects of human performance that relate to plant safety and to develop measures that can be used to successfully assure licensee performance and indicate when additional investigation may be required. This paper presents research that establishes a technical basis for developing human performance measures. In particular, we discuss: 1) how historical data already gives some indication of connection between human performance and overall plant performance, 2) how industry led efforts to measure and model human performance and organizational factors could serve as a data source and basis for a

  1. Meeting human needs

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1992-01-01

    Manned space flight can be viewed as an interaction of three general elements: the human crewmember, spacecraft systems, and the environment. While the human crewmember is a crucial element in the system, certain physiological, psychological, environ- mental and spacecraft systems factors can compromise human performance in space. These factors include atmospheric pressure, physiology, uncertainties associated with space radiation, the potential for exposure to toxic materials in the closed environment, and spacecraft habitability. Health protection in space, for current and future missions, relies on a philosophy of risk reduction, which in the space program is achieved in four ways-through health maintenance, health care, design criteria, an selection and training. Emphasis is place upon prevention, through selection criteria and careful screening. Spacecraft health care systems must be absolutely reliable, and they will be automated and computerized to the maximum extent possible, but still designed with the human crewmember's capabilities in mind. The autonomy and technological sophistication of future missions will require a greater emphasis on high-level interaction between the human operator and automated systems, with effective allocation of tasks between humans and machines. Performance in space will include complex tasks during extravehicular activity (EVA) and on planetary surfaces, and knowledge of crewmembers' capability and limitations during such operations will be critical to mission success. Psychological support will become increasingly important on space missions, as crews spend long periods in remote and potentially hazardous environments. The success of future missions will depend on both individual psychological health and group cohesion and productivity, particularly as crew profiles become more heterogeneous. Thus, further human factors are needed in the area of small-group dynamics and performance.

  2. Spaceflight Human System Standards

    NASA Technical Reports Server (NTRS)

    Holubec, Keith; Tillman, Barry; Connolly, Jan

    2009-01-01

    NASA created a new approach for human system integration and human performance standards. NASA created two documents a standard and a reference handbook. The standard is titled NASA Space Flight Human-System Standard (SFHSS) and consists of two-volumes: Volume 1- Crew Health This volume covers standards needed to support astronaut health (medical care, nutrition, sleep, exercise, etc.) Volume 2 Human Factors, Habitability and Environmental Health This volume covers the standards for system design that will maintain astronaut performance (ie., environmental factors, design of facilities, layout of workstations, and lighting requirements). It includes classic human factors requirements. The new standards document is written in terms so that it is applicable to a broad range of present and future NASA systems. The document states that all new programs prepare system-specific requirements that will meet the general standards. For example, the new standard does not specify a design should accommodate specific percentiles of a defined population. Rather, NASA-STD-3001, Volume 2 states that all programs shall prepare program-specific requirements that define the user population and their size ranges. The design shall then accommodate the full size range of those users. The companion reference handbook, Human Integration Design Handbook (HIDH), was developed to capture the design consideration information from NASA-STD-3000, and adds spaceflight lessons learned, gaps in knowledge, example solutions, and suggests research to further mature specific disciplines. The HIDH serves two major purposes: HIDH is the reference document for writing human factors requirements for specific systems. HIDH contains design guidance information that helps insure that designers create systems which safely and effectively accommodate the capabilities and limitations of space flight crews.

  3. Human Milk Fortification.

    PubMed

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born <32 weeks' gestation prior to discharge home. Recent recommended dietary intakes (RDI) have been revised. Up to 4.2 g of protein and 135 kcal/kg per day is recommended for infants born very preterm. Additional supplements are needed to current commercial fortifiers to achieve these RDI and reduce the incidence of ex-uterine growth failure. A human milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population. PMID:26111568

  4. Why Geo-Humanities

    NASA Astrophysics Data System (ADS)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  5. Archaic human genomics.

    PubMed

    Disotell, Todd R

    2012-01-01

    For much of the 20th century, the predominant view of human evolutionary history was derived from the fossil record. Homo erectus was seen arising in Africa from an earlier member of the genus and then spreading throughout the Old World and into the Oceania. A regional continuity model of anagenetic change from H. erectus via various intermediate archaic species into the modern humans in each of the regions inhabited by H. erectus was labeled the multiregional model of human evolution (MRE). A contrasting model positing a single origin, in Africa, of anatomically modern H. sapiens with some populations later migrating out of Africa and replacing the local archaic populations throughout the world with complete replacement became known as the recent African origin (RAO) model. Proponents of both models used different interpretations of the fossil record to bolster their views for decades. In the 1980s, molecular genetic techniques began providing evidence from modern human variation that allowed not only the different models of modern human origins to be tested but also the exploration demographic history and the types of selection that different regions of the genome and even specific traits had undergone. The majority of researchers interpreted these data as strongly supporting the RAO model, especially analyses of mitochondrial DNA (mtDNA). Extrapolating backward from modern patterns of variation and using various calibration points and substitution rates, a consensus arose that saw modern humans evolving from an African population around 200,000 years ago. Much later, around 50,000 years ago, a subset of this population migrated out of Africa replacing Neanderthals in Europe and western Asia as well as archaics in eastern Asia and Oceania. mtDNA sequences from more than two-dozen Neanderthals and early modern humans re-enforced this consensus. In 2010, however, the complete draft genomes of Neanderthals and of heretofore unknown hominins from Siberia, called

  6. Infants' Responses to Real Humans and Representations of Humans

    ERIC Educational Resources Information Center

    Heron, Michelle; Slaughter, Virginia

    2010-01-01

    Infants' responses to typical and scrambled human body shapes were assessed in relation to the realism of the human body stimuli presented. In four separate experiments, infants were familiarized to typical human bodies and then shown a series of scrambled human bodies on the test. Looking behaviour was assessed in response to a range of different…

  7. Human occupancy detection

    NASA Astrophysics Data System (ADS)

    Brown, David A.

    1994-10-01

    In the area of security and surveillance technologies, the problem of the arrival in Canada of illegal and undesirable ship and truck cargo loads is steadily increasing. As the volumes of cargo arrivals increase so do the Immigration and Customs problems related to the determination of the validity of those cargo contents. Of special concern to Immigration Control Authorities around the world is the emerging and increasing trend of illegal smuggling of human beings hidden inside of shipping containers. Beginning in 1992, Immigration Control Authorities in Canada observed an escalation of alien people smuggling through the use of cargo shipping containers arriving in the Port of Montreal. This paper will present to the audience the recently completed Immigration Canada Human Occupancy Detection project by explaining the design, development and testing of human occupancy detectors. The devices are designed to electronically detect the presence of persons hiding inside of shipping containers, without the requirement of opening the container doors. The human occupancy detection concepts are based upon the presence of carbon dioxide or other human waste characteristics commonly found inside of shipping containers.

  8. Human Spinal Motor Control.

    PubMed

    Nielsen, Jens Bo

    2016-07-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. Humans have direct cortical connections to spinal motoneurons, which bypass spinal interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. PMID:27023730

  9. Human and murine erythropoiesis

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Mohandas, Narla; Gallagher, Patrick G.

    2015-01-01

    Purpose of review Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses. Recent findings The availability of high-throughput genomic methodologies has allowed attainment of detailed gene expression data from cells at varying developmental and differentiation stages of erythropoiesis. Transcriptome analyses of human and murine reveal both stage and species-specific similarities and differences across terminal erythroid differentiation. Erythroid-specific long noncoding RNAs exhibit poor sequence conservation between human and mouse. Genome-wide analyses of alternative splicing reveal that complex, dynamic, stage-specific programs of alternative splicing program are utilized during terminal erythroid differentiation. Transcriptome data provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis. Understanding these processes will provide innovative strategies to detect, diagnose, prevent, and treat hematologic disease. Summary Understanding the shared and different mechanisms controlling human and murine erythropoiesis will allow investigators to leverage the best model system to provide insights in normal and perturbed erythropoiesis. PMID:25719574

  10. The Human Serum Metabolome

    PubMed Central

    Psychogios, Nikolaos; Hau, David D.; Peng, Jun; Guo, An Chi; Mandal, Rupasri; Bouatra, Souhaila; Sinelnikov, Igor; Krishnamurthy, Ramanarayan; Eisner, Roman; Gautam, Bijaya; Young, Nelson; Xia, Jianguo; Knox, Craig; Dong, Edison; Huang, Paul; Hollander, Zsuzsanna; Pedersen, Theresa L.; Smith, Steven R.; Bamforth, Fiona; Greiner, Russ; McManus, Bruce; Newman, John W.; Goodfriend, Theodore; Wishart, David S.

    2011-01-01

    Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology) in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca. PMID:21359215

  11. Human herpesvirus 6.

    PubMed Central

    Braun, D K; Dominguez, G; Pellett, P E

    1997-01-01

    Human herpesvirus 6 variant A (HHV-6A) and human herpesvirus 6 variant B (HHV-6B) are two closely related yet distinct viruses. These visuses belong to the Roseolovirus genus of the betaherpesvirus subfamily; they are most closely related to human herpesvirus 7 and then to human cytomegalovirus. Over 95% of people older than 2 years of age are seropositive for either or both HHV-6 variants, and current serologic methods are incapable of discriminating infection with one variant from infection with the other. HHV-6A has not been etiologically linked to any human disease, but such an association will probably be found soon. HHV-6B is the etiologic agent of the common childhood illness exanthem subitum (roseola infantum or sixth disease) and related febrile illnesses. These viruses are frequently active and associated with illness in immunocompromised patients and may play a role in the etiology of Hodgkin's disease and other malignancies. HHV-6 is a commensal inhabitant of brains; various neurologic manifestations, including convulsions and encephalitis, can occur during primary HHV-6 infection or in immunocompromised patients. HHV-6 and distribution in the central nervous system are altered in patients with multiple sclerosis; the significance of this is under investigation. PMID:9227865

  12. [Human genetics and ethics].

    PubMed

    Zergollern, L

    1990-01-01

    Many new problems and dilemmas have occurred in the practice of medical geneticists with the development of human genetics and its subdisciplines--molecular genetics, ethic genetics and juridical genetics. Devoid of the possibility to get adequate education, genetic informer or better to say, counsellor, although a scientist and a professional who has already formed his ethic attitudes, often finds himself in a dilemma when he has to decide whether a procedure made possible by progress of science is ethical or not. Thus, due to different attitudes, same decision is ethical for some, while for the others it is not. Ethic committees are groups of moral and good people trying to find an objective approach to certain genetic and ethic problems. There are more and more ethically unanswered questions in modern human genetics, and particularly in medical genetics. Medical geneticist-ethicist still encounters numerous problems in his work. These are, for example, experiments with human gametes and embryos, possibilities of hybridization of human gametes with animal gametes, in vitro fertilization, detection of heterozygotes and homozygotes for monogene diseases. early detection of chromosomopathies, substitute mothers, homo and hetero insemination, transplantation of fetal and cadeveric organs, uncontrolled consumption of alcohol and drugs, environmental pollution, etc. It is almost impossible to create a single attitude which shall be shared by all those engaged in human health protection. Therefore, it is best to have a neutral eugenetic attitude which allows free ethical choice of each individual, in any case, for the well-being of man. PMID:2366624

  13. Healthy human gut phageome.

    PubMed

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

  14. Cytological features of choricarcinoma in a Pap smear: A case report and literature review.

    PubMed

    Chen, Xiaowei; Wright, Jason D; Abellar, Rosanna G; Koehne de Gonzalez, Anne; Collins, Nikosa; Wright, Thomas C; Hamele-Bena, Diane

    2016-04-01

    Choriocarcinoma is an aggressive malignant trophoblastic tumor that mostly occurs during reproductive years. Cytological features of choriocarcinoma in gynecologic Pap smears have not been described. Herein, we report a case of choriocarcinoma in a Pap smear of a patient who had a history of choriocarcinoma with metastatic disease. PMID:26712464

  15. Discounting human lives

    SciTech Connect

    Cropper, M.L. ); Portney, P.R.

    1992-09-01

    The future costs of regulatory programs to protect human health are routinely discounted, but the lives they save in the future are not. To shed light on the public's attitude toward the discounting of human lives, researchers at Resources for the Future asked 2,600 individuals to choose between one hypothetical program that would save lives immediately and another that would save lives in 5, 10, 25, 50, or 100 years. From the responses, they inferred the number of lives that must be saved in the future to make people as content as saving one life today, compared this implicit discount rate to the respondents' discount rate for money, and identified several factors that affect discount rates for human lives.

  16. Human factors in aviation

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L. (Editor); Nagel, David C. (Editor)

    1988-01-01

    The fundamental principles of human-factors (HF) analysis for aviation applications are examined in a collection of reviews by leading experts, with an emphasis on recent developments. The aim is to provide information and guidance to the aviation community outside the HF field itself. Topics addressed include the systems approach to HF, system safety considerations, the human senses in flight, information processing, aviation workloads, group interaction and crew performance, flight training and simulation, human error in aviation operations, and aircrew fatigue and circadian rhythms. Also discussed are pilot control; aviation displays; cockpit automation; HF aspects of software interfaces; the design and integration of cockpit-crew systems; and HF issues for airline pilots, general aviation, helicopters, and ATC.

  17. Human nutrition: evolutionary perspectives.

    PubMed

    Barnicot, N A

    2005-01-01

    In recent decades, much new evidence relating to the ape forerunners of modern humans has come to hand and diet appears to be an important factor. At some stage, there must have been a transition from a largely vegetarian ape diet to a modern human hunting economy providing significant amounts of meat. On an even longer evolutionary time scale the change was more complex. The mechanisms of evolutionary change are now better understood than they were in Darwin's time, thanks largely to great advances in genetics, both experimental and theoretical. It is virtually certain that diet, as a major component of the human environment, must have exerted evolutionary effects, but researchers still have little good evidence. PMID:17393680

  18. The Human Toxome Project

    PubMed Central

    Bouhifd, Mounir; Andersen, Melvin E.; Baghdikian, Christina; Boekelheide, Kim; Crofton, Kevin M.; Fornace, Albert J.; Kleensang, Andre; Li, Henghong; Livi, Carolina; Maertens, Alexandra; McMullen, Patrick D.; Rosenberg, Michael; Thomas, Russell; Vantangoli, Marguerite; Yager, James D.; Zhao, Liang; Hartung, Thomas

    2016-01-01

    Summary The Human Toxome Project, funded as an NIH Transformative Research grant 2011–2016, is focused on developing the concepts and the means for deducing, validating and sharing molecular pathways of toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectrometry-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies and bioinformatics are being addressed. In parallel, concepts for annotation, validation and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory test strategies. PMID:25742299

  19. Is humanity suicidal?

    PubMed

    Wilson, E O

    1993-01-01

    The world's fauna and flora has entered a crisis unparalleled since the end of the Mesozoic Era, with the extinction rate of species now elevated to more than a thousand times that existing before the coming of humanity. Scientists and policy makers are ill-prepared to moderate this hemorrhaging, because so little is known of the biology of the Earth's millions of species and because so little effort has been directed toward conservation thus far. With the vanished species will go great potential wealth in scientific knowledge, new products, ecosystems services, and part of the natural world in which the human species originated. The need for new research and improved management is thus urgent. If it is not met, humanity will likely survive, but in a world biologically impoverished for all time. PMID:8155855

  20. Classifying human manipulation behavior.

    PubMed

    Bullock, Ian M; Dollar, Aaron M

    2011-01-01

    This paper presents a taxonomy for detailed classification of human and anthropomorphic manipulation behavior. This hand-centric, motion-centric taxonomy differentiates tasks based on criteria such as object contact, prehension, and the nature of object motion relative to a hand frame. A sub-classification of the most dexterous categories, within-hand manipulation, is also presented, based on the principal axis of object rotation or translation in the hand frame. Principles for categorizing complex, multi-faceted tasks are also presented, along with illustrative examples. We hope that the proposed taxonomy will both establish a standard language around human and anthropomorphic manipulation as well as enable improved understanding of the differences in hand use for a wide variety of behavior. Although designed for human and anthropomorphic hands, the taxonomy might easily be extended to a wide range of robot manipulators and end-effectors. PMID:22275611

  1. Autophagy and human diseases

    PubMed Central

    Jiang, Peidu; Mizushima, Noboru

    2014-01-01

    Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized. PMID:24323045

  2. Helicopter human factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  3. The human toxome project.

    PubMed

    Bouhifd, Mounir; Andersen, Melvin E; Baghdikian, Christina; Boekelheide, Kim; Crofton, Kevin M; Fornace, Albert J; Kleensang, Andre; Li, Henghong; Livi, Carolina; Maertens, Alexandra; McMullen, Patrick D; Rosenberg, Michael; Thomas, Russell; Vantangoli, Marguerite; Yager, James D; Zhao, Liang; Hartung, Thomas

    2015-01-01

    The Human Toxome Project, funded as an NIH Transformative Research grant 2011-2016, is focused on developing the concepts and the means for deducing, validating and sharing molecular pathways of toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectroscopy-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies and bioinformatics are being addressed. In parallel, concepts for annotation, validation and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory test strategies. PMID:25742299

  4. Whither medical humanities?

    PubMed

    Singh, Navjeevan

    2012-01-01

    Understanding the medical humanities (MH) and their role in medical education is in its infancy in India. Students are initiated into professional (medical) education too early in life, usually at the expense of a basic grounding in the humanities, resulting in warped intellectual growth. The author, arguing against the wholesale import of foreign systems, advocates free inquiry by medical educators to evolve a humanities programme for medical students derived from our own cultural context. This essay describes the early experiences of efforts to make a beginning at the University College of Medical Sciences, Delhi. The author reviews the various strategies used and the challenges of introducing the subject to the current generation of medical students. PMID:22864074

  5. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An investigation of the spectrum of space teleoperation activities likely in the 1985 to 1995 decade focused on the resolution of critical human engineering issues and characterization of the technology effect on performance of remote human operators. The study began with the identification and documentation of a set of representative reference teleoperator tasks. For each task, technology, development, and design options, issues, and alternatives that bear on human operator performance were defined and categorized. A literature survey identified existing studies of man/machine issues. For each teleoperations category, an assessment was made of the state of knowledge on a scale from adequate to void. The tests, experiments, and analyses necessary to provide the missing elements of knowledge were then defined. A limited set of tests were actually performed, including operator selection, baseline task definition, control mode study, lighting study, camera study, and preliminary time delay study.

  6. Scientists and Human Rights

    NASA Astrophysics Data System (ADS)

    Makdisi, Yousef

    2012-02-01

    The American Physical Society has a long history of involvement in defense of human rights. The Committee on International Freedom of Scientists was formed in the mid seventies as a subcommittee within the Panel On Public Affairs ``to deal with matters of an international nature that endangers the abilities of scientists to function as scientists'' and by 1980 it was established as an independent committee. In this presentation I will describe some aspects of the early history and the impetus that led to such an advocacy, the methods employed then and how they evolved to the present CIFS responsibility ``for monitoring concerns regarding human rights for scientists throughout the world''. I will also describe the current approach and some sample cases the committee has pursued recently, the interaction with other human rights organizations, and touch upon some venues through which the community can engage to help in this noble cause.

  7. Preparing for Human Exploration

    NASA Technical Reports Server (NTRS)

    Drake, Bret G.; Joosten, B. Kent

    1998-01-01

    NASA's Human Exploration and Development of Space (HEDS) Enterprise is defining architectures and requirements for human exploration that radically reduce the costs of such missions through the use of advanced technologies, commercial partnerships and innovative systems strategies. In addition, the HEDS Enterprise is collaborating with the Space Science Enterprise to acquire needed early knowledge about Mars and to demonstrate critical technologies via robotic missions. This paper provides an overview of the technological challenges facing NASA as it prepares for human exploration. Emphasis is placed on identifying the key technologies including those which will provide the most return in terms of reducing total mission cost and/or reducing potential risk to the mission crew. Top-level requirements are provided for those critical enabling technology options currently under consideration.

  8. Abortion and human rights.

    PubMed

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus. PMID:20303830

  9. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  10. The Exploration of Mars by Humans: Why Mars? Why Humans?

    NASA Technical Reports Server (NTRS)

    Levine, Joel S.

    2011-01-01

    As we commemorate the 50th anniversary of Yuri Gagarin's historic flight in 1961, the first flight of a human in space, plans are underway for another historic human mission. Plans are being developed for a human mission to Mars. Once we reach Mars, the human species will become the first two-planet species. Both the Bush Administration (in 2004) and the Obama Administration (in 2010) proposed a human mission to Mars as a national goal of the United States.

  11. Human Modeling for Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  12. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  13. Cardiovascular Deconditioning in Humans: Human Studies Core

    NASA Technical Reports Server (NTRS)

    Williams, Gordon

    1999-01-01

    Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

  14. Human variation databases

    PubMed Central

    Küntzer, Jan; Eggle, Daniela; Klostermann, Stefan; Burtscher, Helmut

    2010-01-01

    More than 100 000 human genetic variations have been described in various genes that are associated with a wide variety of diseases. Such data provides invaluable information for both clinical medicine and basic science. A number of locus-specific databases have been developed to exploit this huge amount of data. However, the scope, format and content of these databases differ strongly and as no standard for variation databases has yet been adopted, the way data is presented varies enormously. This review aims to give an overview of current resources for human variation data in public and commercial resources. PMID:20639550

  15. Human MSH2 protein

    DOEpatents

    Chapelle, A. de la; Vogelstein, B.; Kinzler, K.W.

    1997-01-07

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error{sup +} (RER{sup +}) tumor cells. 19 figs.

  16. Human MSH2 protein

    DOEpatents

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    1997-01-01

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  17. [Human reservoirs of Pneumocystis].

    PubMed

    Wissmann, Gustavo; Morilla, Ruben; Friaza, Vicente; Calderón, Enrique; Varela, Jose M

    2010-01-01

    Pneumocystis jirovecii, the fungal agent that causes Pneumocystis pneumonia (PCP), is known to exclusively infect humans. Molecular studies have enabled detection of this fungus in individuals who have been colonized by P. jirovecii. Such colonization, found in several populations, seems to act as a human reservoir for the fungus. Various studies have reported mutations associated with sulfa resistance in P. jirovecii strains isolated from colonized patients, who can transmit the mutant genotype to PCP-susceptible individuals. The growing interest in P. jirovecii colonization may prompt the design of new prevention and management strategies for PCP. PMID:19403207

  18. We Are Human Beings.

    PubMed

    McGee, Andrew

    2016-04-01

    In this paper, I examine Jeff McMahan's arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  19. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  20. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  1. Memristance in human skin

    NASA Astrophysics Data System (ADS)

    Martinsen, Ø. G.; Grimnes, S.; Lütken, C. A.; Johnsen, G. K.

    2010-04-01

    The memristor is basically a resistor with memory, so that the resistance is dependent on the net amount of charge having passed through the device. It is the regarded the fourth fundamental component, in addition to the resistor, capacitor and inductor, that can be deduced from the four basic circuit variables; current, voltage, charge and magnetic flux. We show that memristors can be used for modelling electrical properties of human skin. In particular is electro-osmosis in human sweat ducts of memristive nature.

  2. Making IBM's Computer, Watson, Human

    ERIC Educational Resources Information Center

    Rachlin, Howard

    2012-01-01

    This essay uses the recent victory of an IBM computer (Watson) in the TV game, "Jeopardy," to speculate on the abilities Watson would need, in addition to those it has, to be human. The essay's basic premise is that to be human is to behave as humans behave and to function in society as humans function. Alternatives to this premise are considered…

  3. Human Challenges in Exploration Missions

    NASA Technical Reports Server (NTRS)

    Lloyd, Charles W.

    2007-01-01

    This viewgraph presents an overview using pictures some of the history of human exploration of the new frontiers of Earth and then examines some of the challenges to human exploration of space. Particular attention is given to the environmental factors and to the social and human factors that effect humans in space environments.

  4. Designers of Human Settlements

    ERIC Educational Resources Information Center

    Cliff, Ursula

    1976-01-01

    Reviewed herein are the ideas of nine men who have addressed themselves to the problems of human settlements in this century. The ideas reviewed include those of Arnold Toynbee, Lewis Mumford, Hassan Fathy, Buckminster Fuller, Constantinos Doxiadis, Charles Correa, Paul Mwaluko, Robert McNamara and John F. C. Turner. (BT)

  5. The Human Toxome Project

    EPA Science Inventory

    The Human Toxome project, funded as an NIH Transformative Research grant 2011--‐ 2016, is focused on developing the concepts and the means for deducing, validating, and sharing molecular Pathways of Toxicity (PoT). Using the test case of estrogenic endocrine disruption, the respo...

  6. Human neurotrichinellosis, United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parasites of the genus Trichinella are globally-distributed, tissue-dwelling nematodes that predominantly infect mammals, though certain species are known to infect birds and reptiles as well. Human trichinellosis occurs by the ingestion of raw or improperly cooked meat harboring the infective muscl...

  7. Biotechnologies and Human Dignity

    ERIC Educational Resources Information Center

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  8. Learning to Be Human

    ERIC Educational Resources Information Center

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  9. Human Babesiosis, Bolivia, 2013

    PubMed Central

    Gabrielli, Simona; Totino, Valentina; Macchioni, Fabio; Zuñiga, Freddy; Rojas, Patricia; Lara, Yuni; Roselli, Mimmo; Cancrini, Gabriella

    2016-01-01

    To investigate human babesiosis in the Bolivian Chaco, in 2013 we tested blood samples from 271 healthy persons living in 2 rural communities in this region. Microscopy and PCR indicated that 3.3% of persons were positive for Babesia microti parasites (US lineage); seroprevalence was 45.7%. Appropriate screening should mitigate the risk for transfusion-associated babesiosis. PMID:27434696

  10. Occupying the Digital Humanities

    ERIC Educational Resources Information Center

    Rice, Jeff

    2013-01-01

    This essay questions the digital humanities' dependence on interpretation and critique as strategies for reading and responding to texts. Instead, the essay proposes suggestion as a digital rhetorical practice, one that does not replace hermeneutics, but instead offers alternative ways to respond to texts. The essay uses the Occupy movement as an…

  11. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    DNA vaccine for T1D promising in the clinic HPV vaccines halved infections in US teenage girls Modified DC immunotherapy against melanoma New study looks at clinical severity of human H7N9 infections Prevnar vaccines are valuable for healthcare systems GAPVAC: New consortium in the fight of brain cancer Cytomegalovirus vaccine to enter phase 3 Malaria vaccination using chemically attenuated parasites

  12. Human Development Student Modules.

    ERIC Educational Resources Information Center

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This set of 61 student learning modules deals with various topics pertaining to human development. The modules, which are designed for use in performance-based vocational education programs, each contain the following components: an introduction for the student, a performance objective, a variety of learning activities, content information, a…

  13. The Human Potential Movement.

    ERIC Educational Resources Information Center

    Tamashiro, Roy T.

    The advent of the human potential movement has generated the expectation that educators unleash the intellectual, emotional, physical, and spiritual talents of students. This movement is characterized by its focus on (1) the person as a total being, (2) the needs and concerns of students, (3) phenomenology, (4) personal values and goals, and (5)…

  14. Toward a Technical Humanism

    ERIC Educational Resources Information Center

    Malassis, Louis

    1977-01-01

    Examines the relationship between education and development in developing nations. Advocates the fostering of a technical humanism--the development of knowledge in all its forms as a basis for action. In this system, technical education is as highly valued as general education. The system, and its applications to rural education is discussed. (CP)

  15. Television and Human Behavior.

    ERIC Educational Resources Information Center

    Comstock, George; And Others

    To compile a comprehensive review of English language scientific literature regarding the effects of television on human behavior, the authors of this book evaluated more than 2,500 books, articles, reports, and other documents. Rather than taking a traditional approach, the authors followed a new model for the retrieval and synthesis of…

  16. Trends in Humanities Programming.

    ERIC Educational Resources Information Center

    Vavrek, Bernard, Ed.; Whitney, Loralyn, Ed.

    Proceedings from this workshop sponsored by the Center for the Study of Rural Librarianship are intended to disseminate information to assist rural librarians engaged in planning and conducting public programs that explore issues related to the humanities. This report of the proceedings includes the texts of three presented papers, reactions from…

  17. Humanizing the Workplace.

    ERIC Educational Resources Information Center

    Fairfield, Roy P., Ed.

    A series of essays discussing ideas about humanizing work are presented in the document. Three major sections divide the essays, and each includes a preface with comments suggesting the central focus and questions with which the authors are concerned. The first section deals with the history, philosophy, and issues related to work and contains…

  18. Television's New Humane Collectivity.

    ERIC Educational Resources Information Center

    Schrag, Robert L.; And Others

    1981-01-01

    Analyzes "Taxi,""Barney Miller,""Lou Grant," and "M*A*S*H" in terms of three fantasy themes: the realization of significant others, the alliance in action, and membership into personhood. From these themes emerges a rhetorical vision of the new humane collectivity. (PD)

  19. Strategic Human Resource Development.

    ERIC Educational Resources Information Center

    Garavan, Thomas N.

    1991-01-01

    Reviews literature on strategic human resource development (HRD) focusing on the characteristics of such activities, conditions necessary for the promotion of HRD, and the benefits to an organization pursuing such activities. Empirical evidence is presented on HRD policy formation and planning processes in Irish high technology companies. (JOW)

  20. Grass and human nutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Food products from animals that graze grasslands and consume diets high in forages are often better for human health than livestock fed diets with forages and concentrates. Meat from livestock that graze pastures in the United States frequently has less fat and higher concentrations of omega-3 fatty...

  1. Humanism in Education

    ERIC Educational Resources Information Center

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  2. Futures of Human Communication.

    ERIC Educational Resources Information Center

    Harms, L. S.

    There are several research areas basic to the long-range future of human communications. Telecommunication and transportation offer the possiblity of two worldwide communications networks whose interrelationships need to be explored in terms of the needs of the individual, the community, and the world at large. Expanding possibilities of…

  3. Human Papilloma Virus Infections

    PubMed Central

    Wright, V. Cecil

    1989-01-01

    Genital warts are believed to be caused by human papilloma viruses and to be sexually transmitted. The viruses are classified by DNA types, which appear to cause different types of disease. The choice of treatment, and usually its success rate, vary according to the type of disease and its location. PMID:21248973

  4. Marketing Human Resource Development.

    ERIC Educational Resources Information Center

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  5. Strengthening Career Human Agency

    ERIC Educational Resources Information Center

    Chen, Charles P.

    2006-01-01

    Rooted in A. Bandura's (1982, 2001b) social cognitive theory, the notion of human agency has received considerable attention in vocational and career psychology for the last 2 decades, especially with the recent emergence of social constructivist thinking in the field. This article continues in the same direction. In reviewing the notion of human…

  6. Human performance measuring device

    NASA Technical Reports Server (NTRS)

    Michael, J.; Scow, J.

    1970-01-01

    Complex coordinator, consisting of operator control console, recorder, subject display panel, and limb controls, measures human performance by testing perceptual and motor skills. Device measures psychophysiological functions in drug and environmental studies, and is applicable to early detection of psychophysiological body changes.

  7. Independent Human Studies.

    ERIC Educational Resources Information Center

    Kaplan, Suzanne; Wilson, Gordon

    1978-01-01

    The Independent Human Studies program at Schoolcraft College offers an alternative method of earning academic credits. Students delineate an area of study, pose research questions, gather resources, synthesize the information, state the thesis, choose the method of presentation, set schedules, and take responsibility for meeting deadlines. (MB)

  8. Human Learning and Memory

    ERIC Educational Resources Information Center

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  9. Human Memory: The Basics

    ERIC Educational Resources Information Center

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  10. The healthy human microbiome.

    PubMed

    Lloyd-Price, Jason; Abu-Ali, Galeb; Huttenhower, Curtis

    2016-01-01

    Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome-the total DNA content of microbes inhabiting our bodies-is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the "healthy microbiome" has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a 'healthy microbiome' that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future. PMID:27122046

  11. Neurobiology and the Humanities

    PubMed Central

    Zeki, Semir

    2014-01-01

    Can the arts and humanities contribute significantly to the study of the brain? Similar brain processes are involved in humanistic and scientific inference, and in this essay, I argue that conclusions reached by one are relevant to the other. PMID:25277451

  12. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  13. Who Hung the Humanities?

    ERIC Educational Resources Information Center

    Lambert, David

    2013-01-01

    This paper is partly based on a lecture given at the AGTA conference in Perth in January 2013. It argues for a progressive subject based curriculum in which geography plays an essential part. This is based on an analysis of why and how subjects like geography, as part of the humanities, have been undermined and diminished in recent times. In a way…

  14. Humanizing the Secondary School.

    ERIC Educational Resources Information Center

    Hamilton, Norman K., Ed.; Saylor, J. Galen, Ed.

    These papers, presented during ASCD-sponsored conference, confront educators with issues in and alternatives for making secondary schools a more humanizing experience for students. The contributors and their articles are: Norman K. Hamilton, "Alternatives in Secondary Education"; Thornton B. Monez and Norman L. Bussiere, "The High School in Human…

  15. Human Babesiosis, Bolivia, 2013.

    PubMed

    Gabrielli, Simona; Totino, Valentina; Macchioni, Fabio; Zuñiga, Freddy; Rojas, Patricia; Lara, Yuni; Roselli, Mimmo; Bartoloni, Alessandro; Cancrini, Gabriella

    2016-08-01

    To investigate human babesiosis in the Bolivian Chaco, in 2013 we tested blood samples from 271 healthy persons living in 2 rural communities in this region. Microscopy and PCR indicated that 3.3% of persons were positive for Babesia microti parasites (US lineage); seroprevalence was 45.7%. Appropriate screening should mitigate the risk for transfusion-associated babesiosis. PMID:27434696

  16. Human growth hormone.

    PubMed

    Strobl, J S; Thomas, M J

    1994-03-01

    The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID:8190748

  17. Fighting for Human Rights

    ERIC Educational Resources Information Center

    Ong, Bao

    2011-01-01

    Speak Truth To Power consists of 17 teacher-developed lessons based on the stories of rights advocates from all over the world. The lessons were created for sixth-through 12th-grade students, and have come to New York schools thanks to the Robert F. Kennedy Center for Justice and Human Rights and the New York State United Teachers union. Speak…

  18. Developing Human Resources.

    ERIC Educational Resources Information Center

    Nadler, Leonard

    This book attempts to capture the essence of a rapidly emerging field, that of Human Resource Development (HRD). HRD includes improving performance on the present job (training), preparing individuals for future but identifiable jobs within the organization (education), and helping individuals grow to meet future organizational growth…

  19. Fighting for the Humanities

    ERIC Educational Resources Information Center

    Nelson, Cary

    2012-01-01

    The question, "Who will bankroll poetry?", succinctly embodies what is now a widespread recognition that the humanities may have more to lose in the current budget wars than either the sciences or a number of technical fields. The only budget war that can unite individuals, rather than divide them, is one arguing that too much is being spent on…

  20. Communicating with Virtual Humans.

    ERIC Educational Resources Information Center

    Thalmann, Nadia Magnenat

    The face is a small part of a human, but it plays an essential role in communication. An open hybrid system for facial animation is presented. It encapsulates a considerable amount of information regarding facial models, movements, expressions, emotions, and speech. The complex description of facial animation can be handled better by assigning…

  1. Animal and Human Communication.

    ERIC Educational Resources Information Center

    Rummel, Lynda

    Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks man at…

  2. The Humanities, Unraveled

    ERIC Educational Resources Information Center

    Berube, Michael

    2013-01-01

    Graduate education in the humanities is in crisis. Every aspect, from the most specific details of the curriculum to the broadest questions about its purpose, is in crisis. It is a seamless garment of crisis: If one pulls on any one thread, the entire thing unravels. It is therefore exceptionally difficult to discuss any one aspect of graduate…

  3. Antihumanism in the Humanities.

    ERIC Educational Resources Information Center

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  4. Ubiquitous human computing.

    PubMed

    Zittrain, Jonathan

    2008-10-28

    Ubiquitous computing means network connectivity everywhere, linking devices and systems as small as a drawing pin and as large as a worldwide product distribution chain. What could happen when people are so readily networked? This paper explores issues arising from two possible emerging models of ubiquitous human computing: fungible networked brainpower and collective personal vital sign monitoring. PMID:18672463

  5. Humans as Lie Detectors.

    ERIC Educational Resources Information Center

    DePaulo, Bella; And Others

    1980-01-01

    Discusses several studies of whether and how well humans can detect lies. Examines the accuracy of such persons as well as the process of how they actually detect lies, how they think they detect lies, and whether the actual and perceived processes of lie detection correspond to one another. (JMF)

  6. Reconsidering Human Performance Technology

    ERIC Educational Resources Information Center

    Jang, Hwan Young

    2008-01-01

    This article discusses three perceived challenges in the field of human performance technology: a missing link from training to performance, limitations in gap analysis and cause analysis, and a lack of attention to business and organization performance. It then provides possible alternatives for each issue, such as instructional system…

  7. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  8. Radar: Human Safety Net

    ERIC Educational Resources Information Center

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  9. "Healthy" Human Development Indices

    ERIC Educational Resources Information Center

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  10. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  11. Tackling Human Rights

    ERIC Educational Resources Information Center

    McLester, Susan

    2005-01-01

    In 2003, four high school students from the Tashkent International School in the capital city confronted the issue of their nation's human rights problems head on by researching the topic and publishing their findings on the Web. The site, "Uzbekistan: Opaque Reality," was created as an entry for the non-profit Global SchoolNet's Doors to…

  12. The human genome project.

    PubMed Central

    Olson, M V

    1993-01-01

    The Human Genome Project in the United States is now well underway. Its programmatic direction was largely set by a National Research Council report issued in 1988. The broad framework supplied by this report has survived almost unchanged despite an upheaval in the technology of genome analysis. This upheaval has primarily affected physical and genetic mapping, the two dominant activities in the present phase of the project. Advances in mapping techniques have allowed good progress toward the specific goals of the project and are also providing strong corollary benefits throughout biomedical research. Actual DNA sequencing of the genomes of the human and model organisms is still at an early stage. There has been little progress in the intrinsic efficiency of DNA-sequence determination. However, refinements in experimental protocols, instrumentation, and project management have made it practical to acquire sequence data on an enlarged scale. It is also increasingly apparent that DNA-sequence data provide a potent means of relating knowledge gained from the study of model organisms to human biology. There is as yet little indication that the infusion of technology from outside biology into the Human Genome Project has been effectively stimulated. Opportunities in this area remain large, posing substantial technical and policy challenges. PMID:8506271

  13. Human thimet oligopeptidase.

    PubMed Central

    Dando, P M; Brown, M A; Barrett, A J

    1993-01-01

    We have purified human thimet oligopeptidase to homogeneity from erythrocytes, and compared it with the enzyme from rat testis and chicken liver. An antiserum raised against rat thimet oligopeptidase also recognized the human and chicken enzymes, suggesting that the structure of the enzyme has been strongly conserved in evolution. Consistent with this, the properties of the human enzyme were very similar to those for the other species. Thus human thimet oligopeptidase also is a thiol-dependent metallo-oligopeptidase with M(r) about 75,000. Specificity for cleavage of a number of peptides was indistinguishable from that of the rat enzyme, but Ki values for the four potent reversible inhibitors tested were lower. In discussing the results, we consider the determinants of the complex substrate specificity of thimet oligopeptidase. We question whether substrates containing more than 17 amino acid residues are cleaved, as has been suggested. We also point out that the favourable location of a proline residue and a free C-terminus in the substrate may be as important as the hydrophobic residues in the P2, P1 and P3' positions that have been emphasized in the past. Images Figure 1 PMID:8373360

  14. Humanizing the Earth

    ERIC Educational Resources Information Center

    Dubos, Rene J.

    1973-01-01

    By using scientific knowledge and ecological wisdom, new ecosystems can be created which will be more stable, profitable, and favorable to the continued growth of civilization. Nature by itself has not taken care of many problems of ecological interest in past and human intervention is necessary. (PS)

  15. Human Biology: Experimental.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

    Education is a process of adapting to change, and the rate of change is especially rapid in science today. This curriculum in human biology is an alternative to the New York State courses in general and Regents biology, and it has been designed to focus on change from the standpoint of the urban student. It is designed to provide students with…

  16. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  17. Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  18. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    ERIC Educational Resources Information Center

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  19. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  20. The science of unitary human beings and interpretive human science.

    PubMed

    Reeder, F

    1993-01-01

    Natural science and human science are identified as the bases of most nursing theories and research programs. Natural science has been disclaimed by Martha Rogers as the philosophy of science that undergirds her work. The question remains, is the science of unitary human beings an interpretive human science? The author explores the works of Rogers through a dialectic with two human scientists' works. Wilhelm Dilthey's works represent the founding or traditional view, and Jurgen Habermas' works represent a contemporary, reconstructionist view. The ways Rogerian thought contributes to human studies but is distinct from traditional and reconstructionist human sciences are illuminated. PMID:8455869

  1. Zygomycetes in Human Disease

    PubMed Central

    Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J.

    2000-01-01

    The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk

  2. A focus on human flourishing.

    PubMed

    Bunkers, Sandra Schmidt

    2010-10-01

    In this column the author focuses on the concepts of human vulnerability and human flourishing. A parable is presented highlighting the importance of now, the present, in human flourishing. A bioethical, anthropological perspective and a nursing humanbecoming perspective on human flourishing are offered. Nursing education is challenged to emphasize the nursing theories of the discipline to teach the concept of human flourishing. Parse's concept of true presence, the four postulates of humanbecoming, and the humanbecoming community change concepts illuminate a nursing theoretical understanding of human flourishing. PMID:20870999

  3. Human eosinophil transmigration.

    PubMed

    Bazan-Socha, Stanislawa; Zuk, Joanna; Jakiela, Bogdan; Musial, Jacek

    2014-01-01

    In this chapter we describe an optimized eosinophil transmigration assay. Transmigration of purified human peripheral blood eosinophils can be studied using special insert with membrane coated with extracellular matrix components or membrane covered with cells growing as a confluent monolayer, such as vascular endothelial cells of any origin or airway epithelial cells. In our opinion, eosinophil transmigration assay performed through monolayer of human microvascular endothelial cells of lung origin is a suitable tool to estimate the full migratory potential of eosinophils in studies on the pathology of asthma or other respiratory diseases, where eosinophils play important effector functions. This experimental system is easy to perform, simple for optimization, and comparable to in vivo processes occurring during eosinophil migration to the inflammatory sites in lungs. PMID:24986615

  4. [Human dignity revisited].

    PubMed

    Pereira-Menaut, Antonio Carlos; Pereira Sáez, Carolina

    2014-01-01

    Since World War II, human dignity has made its way into many constitutions, bills of rights and international treaties. As its roots can be traced easily back to the Judeo-Christian tradition, and, later on, to the influential Kantian vision, dignity cannot be deemed an entirely new concept. For the same token, it cannot be said that dignity has been entirely alien to the legal realm till 1945. On the other hand, the latest philosophical and anthropological trends, as well as the politicisation of the human being, along with some recent advances in biotechnologies, help to explain its growing presence in the legal world. However, these authors suggest that writing down dignity in legal texts does not fully settle its meaning, not even if such texts are constitutions, and the fact remains that its presence in the judicial reasoning does not always imply being the ratio decidendi, as the study of some relevant judicial decisions shows. PMID:25329413

  5. Autophagosomes and human diseases.

    PubMed

    Beau, Isabelle; Mehrpour, Maryam; Codogno, Patrice

    2011-04-01

    The autophagosome is a double-membrane bound compartment that initiates macroautophagy, a degradative pathway for cytoplasmic material terminating in the lysosomal compartment. The discovery of ATG genes involved in the formation of autophagosomes has greatly increased our understanding of the molecular basis of macroautophagy, and its role in cell function. Macroautophagy plays a pivotal role in cell fitness by removing obsolete organelles and protein aggregates. Its stimulation is an adaptive response to stressful situations, such as nutrient deprivation, intended to maintain a level of ATP compatible with cell survival. Macroautophagy is central for organ homeostasis, embryonic development, and longevity. Malfunctioning autophagy is observed in many human diseases including cancer, neurodegenerative diseases, cardiac and muscular diseases, infectious and inflammatory diseases, diabetes, and obesity. Discovering potential drug therapies that can be used to modulate macroautophagy is a major challenge, and likely to enhance the therapeutic arsenal against many human diseases. PMID:21256243

  6. Human factors workplace considerations

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    Computer workstations assume many different forms and play different functions today. In order for them to assume the effective interface role which they should play they must be properly designed to take into account the ubiguitous human factor. In addition, the entire workplace in which they are used should be properly configured so as to enhance the operational features of the individual workstation where possible. A number of general human factors workplace considerations are presented. This ongoing series of notes covers such topics as achieving comfort and good screen visibility, hardware issues (e.g., mouse maintenance), screen symbology features (e.g., labels, cursors, prompts), and various miscellaneous subjects. These notes are presented here in order to: (1) illustrate how one's workstation can be used to support telescience activities of many other people working within an organization, and (2) provide a single complete set of considerations for future reference.

  7. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  8. Recombinant Human Erythropoietin

    PubMed Central

    Bartels, Claudia; Späte, Kira; Krampe, Henning

    2008-01-01

    Treatment of multiple sclerosis (MS) is still unsatisfactory and essentially non-existing for the progressive course of the disease. Recombinant human erythropoietin (EPO) may be a promising neuroprotective/neuroregenerative treatment of MS. In the nervous system, EPO acts anti-apoptotic, antioxidative, anti-inflammatory, neurotrophic and plasticity-modulating. Beneficial effects have been shown in animal models of various neurological and psychiatric diseases, including different models of experimental autoimmune encephalomyelitis. EPO is also effective in human brain disease, as shown in double-blind placebo-controlled clinical studies on ischemic stroke and chronic schizophrenia. An exploratory study on chronic progressive MS yielded lasting improvement in motor and cognitive performance upon high-dose long-term EPO treatment. PMID:21180577

  9. Posthumanism: beyond humanism?

    PubMed

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots. PMID:25684386

  10. Ancient human microbiomes

    PubMed Central

    Warinner, Christina; Speller, Camilla; Collins, Matthew J.; Lewis, Cecil M.

    2015-01-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and therefore, we lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today. PMID:25559298

  11. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  12. Studying the Human Microbiota.

    PubMed

    Walker, Alan W

    2016-01-01

    There are a range of methodologies available to study the human microbiota, ranging from traditional approaches such as culturing through to state-of-the-art developments in next generation DNA sequencing technologies. The advent of molecular techniques in particular has opened up tremendous new avenues for research, and has galvanised interest in the study of our microbial inhabitants. Given the dazzling array of available options, however, it is important to understand the inherent advantages and limitations of each technique so that the best approach can be employed to address the particular research objective. In this chapter we cover some of the most widely used current techniques in human microbiota research and highlight the particular strengths and caveats associated with each approach. PMID:27161348

  13. [PALEOPATHOLOGY OF HUMAN REMAINS].

    PubMed

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population. PMID:27348992

  14. Secure Distributed Human Computation

    NASA Astrophysics Data System (ADS)

    Gentry, Craig; Ramzan, Zulfikar; Stubblebine, Stuart

    In Peha’s Financial Cryptography 2004 invited talk, he described the Cyphermint PayCash system (see www.cyphermint.com), which allows people without bank accounts or credit cards (a sizeable segment of the U.S. population) to automatically and instantly cash checks, pay bills, or make Internet transactions through publicly-accessible kiosks. Since PayCash offers automated financial transactions and since the system uses (unprotected) kiosks, security is critical. The kiosk must decide whether a person cashing a check is really the person to whom the check was made out, so it takes a digital picture of the person cashing the check and transmits this picture electronically to a central office, where a human worker compares the kiosk’s picture to one that was taken when the person registered with Cyphermint. If both pictures are of the same person, then the human worker authorizes the transaction.

  15. Human freedom and enhancement.

    PubMed

    Heilinger, Jan-Christoph; Crone, Katja

    2014-02-01

    Ideas about freedom and related concepts like autonomy and self-determination play a prominent role in the moral debate about human enhancement interventions. However, there is not a single understanding of freedom available, and arguments referring to freedom are simultaneously used to argue both for and against enhancement interventions. This gives rise to misunderstandings and polemical arguments. The paper attempts to disentangle the different distinguishable concepts, classifies them and shows how they relate to one another in order to allow for a more structured and clearer debate. It concludes in identifying the individual underpinnings and the social conditions of choice and decision-making as particularly salient dimensions of freedom in the ethical debate about human enhancement. PMID:23519909

  16. Human herpesvirus 8.

    PubMed

    Martinelli, Paul T; Tyring, Stephen K

    2002-04-01

    Human herpesvirus 8 (HHV 8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a g2 herpesvirus and the most recently identified human tumor virus. HHV 8 has been consistently implicated in the pathogenesis of all clinical variants of Kaposi's sarcoma, as well as in the plasma cell variant of multicentric Castleman's disease and primary effusion lymphomas. Pathogenicity of the virus is increased in the host who is immunosuppressed, either iatrogenically or through H1V-1 infection. The HHV 8 genome contains several homologues of cellular genes that regulate cell growth and differentiation, and the exact mechanisms of the virus' oncogenicity using molecular piracy are still being investigated and elucidated. In this article, the authors review the epidemiology, transmission, clinical manifestations, and molecular genetics of HHV 8 infection and provide a summary of the current treatment modalities available to the clinician. PMID:12120444

  17. Human-centric sensing.

    PubMed

    Srivastava, Mani; Abdelzaher, Tarek; Szymanski, Boleslaw

    2012-01-13

    The first decade of the century witnessed a proliferation of devices with sensing and communication capabilities in the possession of the average individual. Examples range from camera phones and wireless global positioning system units to sensor-equipped, networked fitness devices and entertainment platforms (such as Wii). Social networking platforms emerged, such as Twitter, that allow sharing information in real time. The unprecedented deployment scale of such sensors and connectivity options ushers in an era of novel data-driven applications that rely on inputs collected by networks of humans or measured by sensors acting on their behalf. These applications will impact domains as diverse as health, transportation, energy, disaster recovery, intelligence and warfare. This paper surveys the important opportunities in human-centric sensing, identifies challenges brought about by such opportunities and describes emerging solutions to these challenges. PMID:22124088

  18. Human behavior in emergencies

    SciTech Connect

    Sorensen, J.H.

    1990-01-01

    Studies were carried out at ORNL to attempt to predict the human response to emergency situations, such as earthquakes and chemical or nuclear disasters. The study includes a literature review, survey of people who have been evacuated, development of a simulation model, survey of US communities, research to support evacuation planning, analysis of variability among organizations, and assessment of flood warning system in Wyoming. Suggestions are given for improving emergency preparedness.

  19. Multichannel Human Body Communication

    NASA Astrophysics Data System (ADS)

    Przystup, Piotr; Bujnowski, Adam; Wtorek, Jerzy

    2016-01-01

    Human Body Communication is an attractive alternative for traditional wireless communication (Bluetooth, ZigBee) in case of Body Sensor Networks. Low power, high data rates and data security makes it ideal solution for medical applications. In this paper, signal attenuation for different frequencies, using FR4 electrodes, has been investigated. Performance of single and multichannel transmission with frequency modulation of analog signal has been tested. Experiment results show that HBC is a feasible solution for transmitting data between BSN nodes.

  20. [The process of humanization].

    PubMed

    Durali, T

    1999-01-01

    As Stefan Zweig expressed the situation of mankind succinctly: There are key moments in history (Sternstunden der Menschheit). Because of their paramount importance their events are minimal. Moreover, among them there are those which are greater in calibre than the ones quoted in Stefan Zweig's Sternstunden der Menschheit. These are the turning points of history. At first glance we can enumerate four major events: first and foremost, the enormous shift of certain communities from food-gathering to agriculture around 8000 BC mainly in Southwest Asia (Mesopotamia). Second, the introduction of the writing system at circa 3500 BC by the Sumerians again in Southwest Asia. Last but not least that tremendous innovation, maybe the greatest in history, once more in western Asia, the emergence of monotheistic religions based on revelation, and the origination of philosophy-science within the realm of the Antique Aegean civilization. Man's basic reality is biotic. He shares this very particularity with all other living beings of this world. Livingness, so far as we know, is a peculiarity of our planet, the Earth. The unfolding of livingness and ultimately the emergence of man as a living being is apparently covered by evolution. Hominization is the biotic, whereas humanization represents the cultural (or spiritual) aspect of becoming the human being. Hominization and humanization complement one another to bring about the human wholeness. Hominization, or put it in another way, the evolutionary aspect is, indeed, not the beginning of the story. There still remains a lower layer, in the ontological sense of the team, to be tackled; and that is the physical one. Just as with every living thing, man's most fundamental building blocks are of a physico-chemical-i.e. subatomic, atomic and molecular-nature. PMID:14598826

  1. Human vestibular evoked responses.

    PubMed

    Muñoz-Gamboa, C; Jiménez-Cruz, J

    1994-01-01

    The results of an experimental series dedicated to the acquisition of human vestibular evoked responses are presented. In these series, manual stimulation is applied to a normal group of subjects with rotational acceleration impulses. Every stimulus is large in magnitude and very short in duration, producing small head movements of only a few degrees through a specially designed head immobilization helmet. Results correspond to middle latency vestibular evoked responses. PMID:7968862

  2. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

    The Office of Exploration has established a process whereby all NASA field centers and other NASA Headquarters offices participate in the formulation and analysis of a wide range of mission strategies. These strategies were manifested into specific scenarios or candidate case studies. The case studies provided a systematic approach into analyzing each mission element. First, each case study must address several major themes and rationale including: national pride and international prestige, advancement of scientific knowledge, a catalyst for technology, economic benefits, space enterprise, international cooperation, and education and excellence. Second, the set of candidate case studies are formulated to encompass the technology requirement limits in the life sciences, launch capabilities, space transfer, automation, and robotics in space operations, power, and propulsion. The first set of reference case studies identify three major strategies: human expeditions, science outposts, and evolutionary expansion. During the past year, four case studies were examined to explore these strategies. The expeditionary missions include the Human Expedition to Phobos and Human Expedition to Mars case studies. The Lunar Observatory and Lunar Outpost to Early Mars Evolution case studies examined the later two strategies. This set of case studies established the framework to perform detailed mission analysis and system engineering to define a host of concepts and requirements for various space systems and advanced technologies. The details of each mission are described and, specifically, the results affecting the advanced technologies required to accomplish each mission scenario are presented.

  3. Dioxins and human toxicity.

    PubMed

    Marinković, Natalija; Pašalić, Daria; Ferenčak, Goran; Gršković, Branka; Stavljenić Rukavina, Ana

    2010-12-01

    The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1.Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants.A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man. PMID:21183436

  4. The human flavoproteome

    PubMed Central

    Lienhart, Wolf-Dieter; Gudipati, Venugopal; Macheroux, Peter

    2013-01-01

    Vitamin B2 (riboflavin) is an essential dietary compound used for the enzymatic biosynthesis of FMN and FAD. The human genome contains 90 genes encoding for flavin-dependent proteins, six for riboflavin uptake and transformation into the active coenzymes FMN and FAD as well as two for the reduction to the dihydroflavin form. Flavoproteins utilize either FMN (16%) or FAD (84%) while five human flavoenzymes have a requirement for both FMN and FAD. The majority of flavin-dependent enzymes catalyze oxidation–reduction processes in primary metabolic pathways such as the citric acid cycle, β-oxidation and degradation of amino acids. Ten flavoproteins occur as isozymes and assume special functions in the human organism. Two thirds of flavin-dependent proteins are associated with disorders caused by allelic variants affecting protein function. Flavin-dependent proteins also play an important role in the biosynthesis of other essential cofactors and hormones such as coenzyme A, coenzyme Q, heme, pyridoxal 5′-phosphate, steroids and thyroxine. Moreover, they are important for the regulation of folate metabolites by using tetrahydrofolate as cosubstrate in choline degradation, reduction of N-5.10-methylenetetrahydrofolate to N-5-methyltetrahydrofolate and maintenance of the catalytically competent form of methionine synthase. These flavoenzymes are discussed in detail to highlight their role in health and disease. PMID:23500531

  5. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  6. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  7. History of Human Parasitology

    PubMed Central

    Cox, F. E. G.

    2002-01-01

    Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come in contact with during our relatively short history on Earth. Our knowledge of parasitic infections extends into antiquity, and descriptions of parasites and parasitic infections are found in the earliest writings and have been confirmed by the finding of parasites in archaeological material. The systematic study of parasites began with the rejection of the theory of spontaneous generation and the promulgation of the germ theory. Thereafter, the history of human parasitology proceeded along two lines, the discovery of a parasite and its subsequent association with disease and the recognition of a disease and the subsequent discovery that it was caused by a parasite. This review is concerned with the major helminth and protozoan infections of humans: ascariasis, trichinosis, strongyloidiasis, dracunculiasis, lymphatic filariasis, loasis, onchocerciasis, schistosomiasis, cestodiasis, paragonimiasis, clonorchiasis, opisthorchiasis, amoebiasis, giardiasis, African trypanosomiasis, South American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, cryptosporidiosis, cyclosporiasis, and microsporidiosis. PMID:12364371

  8. Oxytocin promotes human ethnocentrism.

    PubMed

    De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J

    2011-01-25

    Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence. PMID:21220339

  9. Computing human image annotation.

    PubMed

    Channin, David S; Mongkolwat, Pattanasak; Kleper, Vladimir; Rubin, Daniel L

    2009-01-01

    An image annotation is the explanatory or descriptive information about the pixel data of an image that is generated by a human (or machine) observer. An image markup is the graphical symbols placed over the image to depict an annotation. In the majority of current, clinical and research imaging practice, markup is captured in proprietary formats and annotations are referenced only in free text radiology reports. This makes these annotations difficult to query, retrieve and compute upon, hampering their integration into other data mining and analysis efforts. This paper describes the National Cancer Institute's Cancer Biomedical Informatics Grid's (caBIG) Annotation and Image Markup (AIM) project, focusing on how to use AIM to query for annotations. The AIM project delivers an information model for image annotation and markup. The model uses controlled terminologies for important concepts. All of the classes and attributes of the model have been harmonized with the other models and common data elements in use at the National Cancer Institute. The project also delivers XML schemata necessary to instantiate AIMs in XML as well as a software application for translating AIM XML into DICOM S/R and HL7 CDA. Large collections of AIM annotations can be built and then queried as Grid or Web services. Using the tools of the AIM project, image annotations and their markup can be captured and stored in human and machine readable formats. This enables the inclusion of human image observation and inference as part of larger data mining and analysis activities. PMID:19964202

  10. Volcanoes and human history

    NASA Astrophysics Data System (ADS)

    Cashman, K. V.; Giordano, G.

    2008-10-01

    The study of volcanic hazards leads inevitably to questions of how past cultures have lived in volcanically active regions of the world. Here we summarize linkages between volcanological, archaeological and anthropological studies of historic and prehistoric volcanic eruptions, with the goal of evaluating the impact of past eruptions on human populations to better prepare for future events. We use examples from papers collected in this volume to illustrate ways in which volcanological studies aid archaeological investigations by providing basic stratigraphic markers and information about the nature and timing of specific volcanic events. We then turn to archaeological perspectives, which provide physical evidence of the direct impacts of volcanic eruptions, such as site abandonment and human migration, as well as indirect impacts on local cultures as reflected in human artifacts. Finally we review anthropological studies of societal responses to past and recent volcanic eruptions. We pay particular attention to both the psychological impact of catastrophic events and records of these impacts encoded within oral traditions. Taken together these studies record drastic short-term eruption impacts but adaptation to volcanic activity over the longer term, largely through strategies of adaptive land use.

  11. Unusual infections in humans.

    PubMed Central

    Neafie, R C; Marty, A M

    1993-01-01

    Nine cases of unusual infections in humans are presented. In each case, we present the clinical history, histopathologic changes (if indicated), morphologic features of the causative organism, diagnosis, discussion, differential diagnosis, therapy, and current literature. All of the cases are illustrated with pertinent photographs. The nine cases are as follows: (i) acanthocephaliasis, the first acquired human infection by Moniliformis moniliformis in the United States; (ii) dipylidiasis, an uncommon infection caused by the dog tapeworm, Dipylidium caninum; (iii) granulomatous amebic encephalitis, caused by the recently identified leptomyxid group of amebae; (iv) schistosomiasis, a dual infection of the urinary bladder with the rare presentation of both adult worms and eggs of Schistosoma haematobium and Schistosoma mansoni in tissue sections; (v) syphilitic gastritis, an uncommon presentation of Treponema pallidum infection, in a patient with an additional incidental infection by Helicobacter pylori; (vi) microsporidiosis, the only infection caused by a Pleistophora sp. in humans; (vii) sporotrichosis, a rare disseminated infection caused by Sporothrix schenckii with numerous yeast cells in the scrotum; (viii) angiostrongyliasis, the first and only infection caused by Angiostrongylus costaricensis acquired in either Puerto Rico or the United States; and (ix) botryomycosis of the skin and subcutaneous tissue, caused by gram-positive cocci with an unusually large number of granules. Images PMID:8457979

  12. Science and Human Experience

    NASA Astrophysics Data System (ADS)

    Cooper, Leon N.

    2014-12-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  13. Science and Human Experience

    NASA Astrophysics Data System (ADS)

    Cooper, Leon N.

    2015-01-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  14. Gas hydrate and humans

    USGS Publications Warehouse

    Kvenvolden, K.A.

    2000-01-01

    The potential effects of naturally occurring gas hydrate on humans are not understood with certainty, but enough information has been acquired over the past 30 years to make preliminary assessments possible. Three major issues are gas hydrate as (1) a potential energy resource, (2) a factor in global climate change, and (3) a submarine geohazard. The methane content is estimated to be between 1015 to 1017 m3 at STP and the worldwide distribution in outer continental margins of oceans and in polar regions are significant features of gas hydrate. However, its immediate development as an energy resource is not likely because there are various geological constraints and difficult technological problems that must be solved before economic recovery of methane from hydrate can be achieved. The role of gas hydrate in global climate change is uncertain. For hydrate methane to be an effective greenhouse gas, it must reach the atmosphere. Yet there are many obstacles to the transfer of methane from hydrate to the atmosphere. Rates of gas hydrate dissociation and the integrated rates of release and destruction of the methane in the geo/hydro/atmosphere are not adequately understood. Gas hydrate as a submarine geohazard, however, is of immediate and increasing importance to humans as our industrial society moves to exploit seabed resources at ever-greater depths in the waters of our coastal oceans. Human activities and installations in regions of gas-hydrate occurrence must take into account the presence of gas hydrate and deal with the consequences of its presence.

  15. Human milk banking.

    PubMed

    O'Hare, Esther Marie; Wood, Angela; Fiske, Elizabeth

    2013-01-01

    Forms of human milk banking and donation have been present for more than a century worldwide, but, since 1985, the Human Milk Banking Association of North America (HM BANA) has established guidelines to make the use of donor's breast milk safe and the second best form of feeding to maternal breast milk for a neonatal intensive care unit (NICU) infant. The Indiana Mother's Human Milk Bank provides an extensive and meticulous process of selecting breast milk donors. The process begins with a phone interview with a potential donor and includes the review of the donor's medical records, blood laboratory screening, medication and dietary intake, as well as consent from the donor's pediatrician. The milk bank follows steps of collecting, storing, and receiving the breast milk in accordance with the guidelines of the HM BANA. Pasteurization is the method used to ensure the proper heating and cooling of breast milk. Despite the rigorous pasteurization method, the donor's breast milk will not lose most of the important beneficial components needed for sick or ill NICU infants. Every batch of pasteurized breast milk will be cultured for any possible contamination and shipped to NICUs after it has been cleared by laboratory testing. PMID:23666187

  16. Human cryptosporidiosis in Europe.

    PubMed

    Cacciò, S M; Chalmers, R M

    2016-06-01

    Cryptosporidium has emerged as a significant cause of diarrhoeal disease worldwide, with severe health consequences for very young, malnourished children living in endemic areas and for individuals with highly impaired T-cell functions. In Europe, as elsewhere, the burden of disease has been difficult to measure as a result of the lack of appropriate, standardized surveillance and monitoring systems. The recent occurrence of large water- and foodborne outbreaks in several EU countries, as well as the results of many surveys of human and animal cryptosporidiosis, indicate that this parasite is widespread. Specific subtypes of the zoonotic Cryptosporidium parvum and the anthroponotic C. hominis are responsible for the majority of human cases in Europe. No treatment is currently available to clear the infection, but recent progress in genetic engineering of the parasite, coupled with advances in genomics, have opened important avenues for future research. Here we explore the possible reasons for underascertainment of cryptosporidiosis and the importance of accurate diagnosis in clinical management, the epidemiology of human cryptosporidiosis and key messages from recent outbreaks to highlight important interventions and emerging public health issues. PMID:27172805

  17. Mapping the human genome

    SciTech Connect

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  18. Human Provenancing: It's Elemental…

    NASA Astrophysics Data System (ADS)

    Meier-Augenstein, Wolfram; Kemp

    2009-04-01

    Forensic science already uses a variety of methods often in combination to determine a deceased person's identity if neither personal effects nor next of kin (or close friends) can positively identify the victim. While disciplines such as forensic anthropology are able to work from a blank canvass as it were and can provide information on age, gender and ethnical grouping, techniques such as DNA profiling do rely on finding a match either in a database or a comparative sample presumed to be an ante-mortem sample of the victim or from a putative relation. Chances for either to succeed would be greatly enhanced if information gained from a forensic anthropological examination and, circumstances permitting a facial reconstruction could be linked to another technique that can work from a blank canvass or at least does not require comparison to a subject specific database. With the help of isotope ratio mass spectrometry even the very atoms from which a body is made can be used to say something about a person that will help to focus human identification using traditional techniques such as DNA, fingerprints and odontology. Stable isotope fingerprinting works on the basis that almost all chemical elements and in particular the so-called light elements such as carbon (C) that comprise most of the human body occur naturally in different forms, namely isotopes. 2H isotope abundance values recorded by the human body through food and drink ultimately reflect averaged isotopic composition of precipitation or ground water. Stable isotope analysis of 2H isotopic composition in different human tissue such as hair, nails, bone and teeth enables us to construct a time resolved isotopic profile or ‘fingerprint' that may not necessarily permit direct identification of a murder victim or mass disaster victim but in conjunction with forensic anthropological information will provide sufficient intelligence to construct a profile for intelligence lead identification stating where a

  19. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

    Report presents survey of state of art in human factors in automation of aircraft operation. Presents examination of aircraft automation and effects on flight crews in relation to human error and aircraft accidents.

  20. Administrative Aspects of Human Experimentation.

    ERIC Educational Resources Information Center

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  1. Humane Education: A Curriculum Approach.

    ERIC Educational Resources Information Center

    Pearce, Robert W.

    1980-01-01

    Describes a curriculum-based approach to humane education and addresses the role of humane education in the school curriculum as well as the relationship's of education to other facets of animal welfare work. (Author/DS)

  2. Oceans and Human Health Center

    MedlinePlus

    ocean and human health science can help prevent disease outbreaks and improve public health through a deeper understanding of the causes ... our Center and the field of oceans and human health science. More Research Learn about the research ...

  3. About Human Parainfluenza Viruses (HPIVs)

    MedlinePlus

    ... Overview Laboratory Diagnosis HPIV Seasons Resources & References About Human Parainfluenza Viruses (HPIVs) Recommend on Facebook Tweet Share ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov Top

  4. Endogenous Retroviruses and Human Evolution

    PubMed Central

    Lebedev, Yuri; Sverdlov, Eugene

    2002-01-01

    Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor-binding sites. Thus, they can influence the expression of nearby human genes. All known human-specific LTRs belong to the HERV-K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions. PMID:18629260

  5. American Society of Human Genetics

    MedlinePlus

    ... Research Awards August 9, 2016 Media Advisory: American Society of Human Genetics 2016 Annual Meeting July 26, ... McKusick Leadership Award June 30, 2016 The American Society of Human Genetics, Incorporated 9650 Rockville Pike • Bethesda, ...

  6. Human Research Program (HRP) Overview

    NASA Video Gallery

    The Human Research Program (HRP) is a major part of the Space Life and Physical Sciences Research and Applications Division within the Human Exploration and Operations Mission Directorate (HEOMD). ...

  7. DEMONSTRATION OF HUMAN EXPOSURE TOOLS

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) of the National Exposure Research Laboratory (NERL) conducts research on exposure measurements, human activity patterns, exposure and dose models, and cumulative exposures critical for the Agency to make scientificall...

  8. Fire Control and Human Evolution.

    ERIC Educational Resources Information Center

    Russell, Claire

    1978-01-01

    Briefly outlines some aspects of the discovery of fire control by primitive people, such as the preadaptation for speech, the evolution of the human brain, and natural selection for human nakedness or loss of hair. (CS)

  9. Genes, Environment, and Human Behavior.

    ERIC Educational Resources Information Center

    Bloom, Mark V.; Cutter, Mary Ann; Davidson, Ronald; Dougherty, Michael J.; Drexler, Edward; Gelernter, Joel; McCullough, Laurence B.; McInerney, Joseph D.; Murray, Jeffrey C.; Vogler, George P.; Zola, John

    This curriculum module explores genes, environment, and human behavior. This book provides materials to teach about the nature and methods of studying human behavior, raise some of the ethical and public policy dilemmas emerging from the Human Genome Project, and provide professional development for teachers. An extensive Teacher Background…

  10. The Humanities at Triton College.

    ERIC Educational Resources Information Center

    Jacot, Robert E.; Prendergast, Nancy E.

    Designed to assist college personnel in assessing program needs, this report provides an overview of the humanities programs at Triton College. Part I focuses on curricular humanities programs, including discussions of the role and objectives of the School of Arts and Sciences; humanities courses offered in the school; special humanities…

  11. Leadership in a Humane Organization

    ERIC Educational Resources Information Center

    Dimitrov, Danielle

    2015-01-01

    Purpose: The purpose of this paper is to explore the way leadership influences an organization to become humane through its features and behaviors; as well as the organizational circumstances in which humane leadership can be nurtured. The first empirical case study, in the fields of Human Resource Development (HRD) and hospitality management, to…

  12. Making Human Resource Consulting Visible.

    ERIC Educational Resources Information Center

    Kaufmann, Ken; Weaver, Carol L.

    2000-01-01

    Discusses the need for human resources consulting to be seen and understood in order to help achieve business objectives. Presents a model that uses core competencies to tie human resources programs to business strategies, thus positioning human resources as a strategic partner in an enterprise. (LRW)

  13. Literacy as a Human Problem.

    ERIC Educational Resources Information Center

    Raymond, James C., Ed.

    First presented as papers in a symposium on literacy conducted at the University of Alabama, essays in this volume explore three areas of human literacy--law, linguistics, and the English language; testing; and literacy's relation with culture and human consciousness. Following an introduction examining literacy as a human problem, the following…

  14. Gender Aspects of Human Security

    ERIC Educational Resources Information Center

    Moussa, Ghada

    2008-01-01

    The chapter deals with the gender dimensions in human security through focusing on the relationship between gender and human security, first manifested in international declarations and conventions, and subsequently evolving in world women conferences. It aims at analysing the various gender aspects in its relation to different human security…

  15. A Hierarchy of Human Rights.

    ERIC Educational Resources Information Center

    Brockett, Charles

    To establish an objective conception of human rights, one must first identify basic needs intrinsic to all people and then determine whether these needs are or can be hierarchically ordered. Many scholars have conducted research on the concept of human needs, particularly in the area of human rights. Among these scholars are Abraham H. Maslow…

  16. Human Rights and Public Education

    ERIC Educational Resources Information Center

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  17. Community College Humanities Review, 1999.

    ERIC Educational Resources Information Center

    Scheper, George L., Ed.

    1999-01-01

    This special issue of the Community College Humanities Review contains articles generated by National Endowment for the Humanities Summer Institutes, held over several years. The institutes provided opportunities for academics from a variety of humanities disciplines and types of institutions to interact over an extended period of common study of…

  18. NASA Space Human Factors Program

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  19. Generation of improved humanized mouse models for human infectious diseases

    PubMed Central

    Brehm, Michael A.; Wiles, Michael V.; Greiner, Dale L.; Shultz, Leonard D.

    2014-01-01

    The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rgnull) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines. PMID:24607601

  20. Human microsporidial infections.

    PubMed Central

    Weber, R; Bryan, R T; Schwartz, D A; Owen, R L

    1994-01-01

    Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing

  1. Human due diligence.

    PubMed

    Harding, David; Rouse, Ted

    2007-04-01

    Most companies do a thorough job of financial due diligence when they acquire other companies. But all too often, deal makers simply ignore or underestimate the significance of people issues in mergers and acquisitions. The consequences are severe. Most obviously, there's a high degree of talent loss after a deal's announcement. To make matters worse, differences in decision-making styles lead to infighting; integration stalls; and productivity declines. The good news is that human due diligence can help companies avoid these problems. Done early enough, it helps acquirers decide whether to embrace or kill a deal and determine the price they are willing to pay. It also lays the groundwork for smooth integration. When acquirers have done their homework, they can uncover capability gaps, points of friction, and differences in decision making. Even more important, they can make the critical "people" decisions-who stays, who goes, who runs the combined business, what to do with the rank and file-at the time the deal is announced or shortly thereafter. Making such decisions within the first 30 days is critical to the success of a deal. Hostile situations clearly make things more difficult, but companies can and must still do a certain amount of human due diligence to reduce the inevitable fallout from the acquisition process and smooth the integration. This article details the steps involved in conducting human due diligence. The approach is structured around answering five basic questions: Who is the cultural acquirer? What kind of organization do you want? Will the two cultures mesh? Who are the people you most want to retain? And how will rank-and-file employees react to the deal? Unless an acquiring company has answered these questions to its satisfaction, the acquisition it is making will be very likely to end badly. PMID:17432159

  2. Morbilliviruses and human disease.

    PubMed

    Rima, Bertus K; Duprex, W Paul

    2006-01-01

    Morbilliviruses are a group of viruses that belong to the family Paramyxoviridae. The most instantly recognizable member is measles virus (MV) and individuals acutely infected with the virus exhibit a wide range of clinical symptoms ranging from a characteristic mild self-limiting infection to death. Canine distemper virus (CDV) and rinderpest virus (RPV) cause a similar but distinctive pathology in dogs and cattle, respectively, and these, alongside experimental MV infection of primates, have been useful models for MV pathogenesis. Traditionally, viruses were identified because a distinctive disease was observed in man or animals; an infectious agent was subsequently isolated, cultured, and this could be used to recapitulate the disease in an experimentally infected host. Thus, satisfying Koch's postulates has been the norm. More recently, particularly due to the advent of exceedingly sensitive molecular biological assays, many researchers have looked for infectious agents in disease conditions for which a viral aetiology has not been previously established. For these cases, the modified Koch's postulates of Bradford Hill have been developed as criteria to link a virus to a specific disease. Only in a few cases have these conditions been fulfilled. Therefore, many viruses have over the years been definitely and tentatively linked to human diseases and in this respect the morbilliviruses are no different. In this review, human diseases associated with morbillivirus infection have been grouped into three broad categories: (1) those which are definitely caused by the infection; (2) those which may be exacerbated or facilitated by an infection; and (3) those which currently have limited, weak, unsubstantiated or no credible scientific evidence to support any link to a morbillivirus. Thus, an attempt has been made to clarify the published data and separate human diseases actually linked to morbilliviruses from those that are merely anecdotally associated. PMID:16362981

  3. Human adaptation to smog

    SciTech Connect

    Evans, G.W. Jacobs, S.V.; Frager, N.B.

    1982-10-01

    This study examined the health effects of human adaptation to photochemical smog. A group of recent arrivals to the Los Angeles air basin were compared to long-term residents of the basin. Evidence for adaptation included greater irritation and respiratory problems among the recent arrivals and desensitization among the long-term residents in their judgments of the severity of the smog problem to their health. There was no evidence for biochemical adaptation as measured by hemoglobin response to oxidant challenge. The results were discussed in terms of psychological adaption to chronic environmental stressors.

  4. Human portable preconcentrator system

    DOEpatents

    Linker, Kevin L.; Bouchier, Francis A.; Hannum, David W.; Rhykerd, Jr., Charles L.

    2003-01-01

    A preconcentrator system and apparatus suited to human portable use wherein sample potentially containing a target chemical substance is drawn into a chamber and through a pervious screen. The screen is adapted to capture target chemicals and then, upon heating, to release those chemicals into the chamber. Chemicals captured and then released in this fashion are then carried to a portable chemical detection device such as a portable ion mobility spectrometer. In the preferred embodiment, the means for drawing sample into the chamber comprises a reversible fan which, when operated in reverse direction, creates a backpressure that facilitates evolution of captured target chemicals into the chamber when the screen is heated.

  5. [Human castration: historical notes].

    PubMed

    Serarcangeli, C; Rispoli, G

    2001-01-01

    Human castration has been performed from early times for different reasons: to punish and revenge, to display one's religious fanaticism, to protect or to control women, for eunuchs' trade, for therapeutical purposes. In early modern times men were castrated to obtain sopranos voices, or for eugenic or racial reasons. Nowadays chemical castration is used as a therapeutic treatment or as a way to punish rape and other criminal behaviours. Castration is surgical or chemical act that may obviously cause serious physical and psychological consequences. PMID:12375586

  6. Human Outreach through Physics

    NASA Astrophysics Data System (ADS)

    Kant Shukla, Padma

    2006-10-01

    In this talk unique methods for human outreach through physics are described. The focus is on identifying young talented researchers and colleagues around the globe and nourish them for the purpose of diffusing physics knowledge. The goal can be achieved through the organization of international conferences, workshops, seminars, and colleagues, at different locations, invite young and experienced researchers to those meetings, invite them to your home institution, in addition to visiting their universities/laboratories for mentoring and exchanging physics knowledge. The scientific part shall deal with collective processes and coherent nonlinear effects in space and laboratory plasmas.

  7. Human Immunodeficiency Virus Prevention.

    PubMed

    Davis, Teaniese Latham; DiClemente, Ralph

    2016-04-01

    Human immunodeficiency virus (HIV) is the virus that causes AIDS. Surveillance data from 2012 indicate an estimated 1.2 million people aged 13 years and older were living with HIV infection in the United States, and 12.8% do not know their status. There are approximately 50,000 new HIV infections annually. With no available cure for HIV, primary prevention to reduce incident cases of HIV is essential. Strategies to prevent HIV transmission include reducing sexual risk behavior and needle sharing. The Centers for Disease Control and Prevention has multiple resources available for primary and secondary prevention to reduce disease transmission and severity. PMID:26980130

  8. Book Review: Human Radiosensitivity

    SciTech Connect

    Morgan, William F.

    2013-11-01

    This well written report reviews the evidence for variation in human sensitivity to ionizing radiation from epidemiological, clinical, animal, and experimental studies. The report also considers the mechanism(s) of radiation sensitivity and the ethical implications of current and potential knowledge that might be gained in the future. The report is concisely written, considers a large number of historical as well as recent studies, and features a ‘ bullet like ’ summary at the end of each chapter that captures the salient points.

  9. Human Genome Program

    SciTech Connect

    Not Available

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  10. Human Transposon Tectonics

    PubMed Central

    Burns, Kathleen H.; Boeke, Jef D.

    2012-01-01

    Mobile DNAs have had a central role in shaping our genome. More than half of our DNA is comprised of interspersed repeats resulting from replicative copy and paste events of retrotransposons. Although most are fixed, incapable of templating new copies, there are important exceptions to retrotransposon quiescence. De novo insertions cause genetic diseases and cancers, though reliably detecting these occurrences has been difficult. New technologies aimed at uncovering polymorphic insertions reveal that mobile DNAs provide a substantial and dynamic source of structural variation. Key questions going forward include the how and how much new transposition events affect human health and disease. PMID:22579280

  11. HUMAN MACHINE COOPERATIVE TELEROBOTICS

    SciTech Connect

    William R. Hamel; Spivey Douglass; Sewoong Kim; Pamela Murray; Yang Shou; Sriram Sridharan; Ge Zhang; Scott Thayer; Rajiv V. Dubey

    2003-06-30

    The remediation and deactivation and decommissioning (D&D) of nuclear waste storage tanks using telerobotics is one of the most challenging tasks faced in environmental cleanup. Since a number of tanks have reached the end of their design life and some of them have leaks, the unstructured, uncertain and radioactive environment makes the work inefficient and expensive. However, the execution time of teleoperation consumes ten to hundred times that of direct contact with an associated loss in quality. Thus, a considerable effort has been expended to improve the quality and efficiency of telerobotics by incorporating into teleoperation and robotic control functions such as planning, trajectory generation, vision, and 3-D modeling. One example is the Robot Task Space Analyzer (RTSA), which has been developed at the Robotics and Electromechanical Systems Laboratory (REMSL) at the University of Tennessee in support of the D&D robotic work at the Oak Ridge National Laboratory and the National Energy Technology Laboratory. This system builds 3-D models of the area of interest in task space through automatic image processing and/or human interactive manual modeling. The RTSA generates a task plan file, which describes the execution of a task including manipulator and tooling motions. The high level controller of the manipulator interprets the task plan file and executes the task automatically. Thus, if the environment is not highly unstructured, a tooling task, which interacts with environment, will be executed in the autonomous mode. Therefore, the RTSA not only increases the system efficiency, but also improves the system reliability because the operator will act as backstop for safe operation after the 3-D models and task plan files are generated. However, unstructured conditions of environment and tasks necessitate that the telerobot operates in the teleoperation mode for successful execution of task. The inefficiency in the teleoperation mode led to the research

  12. Nongenital human papillomavirus disease.

    PubMed

    Mayeaux, E J; Khan, Michelle J

    2013-06-01

    Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease. PMID:23732034

  13. Machines Imitating Humans

    NASA Astrophysics Data System (ADS)

    Zia-Ul-Haque, Qazi S. M.; Wang, Zhiliang; Zhang, Xueyuan

    The authors have synthesized the emotion in the speech of robot. The modeling of emotion in speech relies on a number of parameters among others, fundamental frequency (F0) level, voice quality, or articulation precision etc. As an initial work for synthesizing emotion in speech, we utilized the three voice features provided by the TTS engine of Microsoft Speech SDK i.e. pitch, rate and volume. Speech with these parameters controlled, was generated randomly with 20 sentences for each emotion and perception by human hearers were collected.

  14. Investigating human evolutionary history

    PubMed Central

    WOOD, BERNARD

    2000-01-01

    We rely on fossils for the interpretation of more than 95% of our evolutionary history. Fieldwork resulting in the recovery of fresh fossil evidence is an important component of reconstructing human evolutionary history, but advances can also be made by extracting additional evidence for the existing fossil record, and by improving the methods used to interpret the fossil evidence. This review shows how information from imaging and dental microstructure has contributed to improving our understanding of the hominin fossil record. It also surveys recent advances in the use of the fossil record for phylogenetic inference. PMID:10999269

  15. Structure of human adenovirus

    SciTech Connect

    Nemerow, Glen R.; Stewart, Phoebe L.; Reddy, Vijay S.

    2012-07-11

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 {angstrom} resolution. The virus structure revealed the location, folds, and interactions of major and minor (cement proteins) on the inner and outer capsid surface. This new structural information sheds further light on the process of adenovirus capsid assembly and virus-host cell interactions.

  16. Photosensitive Human Syndromes

    PubMed Central

    Spivak, Graciela; Hanawalt, Philip C.

    2014-01-01

    Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with sunlight to produce toxic mediators, and by immune reactions to sunlight exposures. Deficiencies in DNA repair and the processing of damaged DNA during replication and transcription may result in mutations and genomic instability. We will review current understanding of photosensitivity to short wavelength ultraviolet light (UV) due to genetic defects in particular DNA repair pathways; deficiencies in some are characterized by an extremely high incidence of cancer in sun-exposed tissues, while in others no cancers have been reported. PMID:26255937

  17. Photosensitive human syndromes.

    PubMed

    Spivak, Graciela; Hanawalt, Philip C

    2015-06-01

    Photosensitivity in humans can result from defects in repair of light-induced DNA lesions, from photoactivation of chemicals (including certain medications) with sunlight to produce toxic mediators, and by immune reactions to sunlight exposures. Deficiencies in DNA repair and the processing of damaged DNA during replication and transcription may result in mutations and genomic instability. We will review current understanding of photosensitivity to short wavelength ultraviolet light (UV) due to genetic defects in particular DNA repair pathways; deficiencies in some are characterized by an extremely high incidence of cancer in sun-exposed tissues, while in others no cancers have been reported. PMID:26255937

  18. Ancient human DNA.

    PubMed

    Kirsanow, Karola; Burger, Joachim

    2012-01-20

    The contribution of palaeogenetic data to the study of various aspects of hominin biology and evolution has been significant, and has the potential to increase substantially with the widespread implementation of next generation sequencing techniques. Here we discuss the present state-of-the-art of ancient human DNA analysis and the characteristics of hominin aDNA that make sequence validation particularly complex. A brief overview of the development of anthropological palaeogenetic analysis is given to illustrate the technical challenges motivating recent technological advancements. PMID:22169595

  19. Is dissection humane?

    PubMed Central

    Hasan, Tabinda

    2011-01-01

    Dissection is being jeopardized in the modern medical education. It has unrelentingly faced the lashes of time and has been the scapegoat for numerous convenient curricula reforms and subjective biases. The cadaver is unparallel in establishing core knowledge among the medical community and it needs to be appreciated in a new light in the “cyber anatomy” realm of today. This article elucidates the medical and ethical validity of continuing human body dissection in medicine which outweighs all the prejudices associated with it. PMID:23908746

  20. Human Exploration of Mars

    NASA Astrophysics Data System (ADS)

    Gwynne, Owen; McKay, Chris; Zubrin, Robert

    1991-06-01

    Novel approaches to the human exploration of Mars are considered with emphasis on a space suit design, extraterrestrial surface mobility, and water supply. A possible way of transporting personnel on the surface of Mars uses a suborbital rocket that will hop from one site to the next, refuelling each time it lands and giving the Martian explorers effective global mobility. Telepresence could be used to avoid limiting the people on Mars to a small exploration area as a result of a lack of transportation infrastructure. Drawings and photographs are included.

  1. Mentoring Human Performance - 12480

    SciTech Connect

    Geis, John A.; Haugen, Christian N.

    2012-07-01

    Although the positive effects of implementing a human performance approach to operations can be hard to quantify, many organizations and industry areas are finding tangible benefits to such a program. Recently, a unique mentoring program was established and implemented focusing on improving the performance of managers, supervisors, and work crews, using the principles of Human Performance Improvement (HPI). The goal of this mentoring was to affect behaviors and habits that reliably implement the principles of HPI to ensure continuous improvement in implementation of an Integrated Safety Management System (ISMS) within a Conduct of Operations framework. Mentors engaged with personnel in a one-on-one, or one-on-many dialogue, which focused on what behaviors were observed, what factors underlie the behaviors, and what changes in behavior could prevent errors or events, and improve performance. A senior management sponsor was essential to gain broad management support. A clear charter and management plan describing the goals, objectives, methodology, and expected outcomes was established. Mentors were carefully selected with senior management endorsement. Mentors were assigned to projects and work teams based on the following three criteria: 1) knowledge of the work scope; 2) experience in similar project areas; and 3) perceived level of trust they would have with project management, supervision, and work teams. This program was restructured significantly when the American Reinvestment and Recovery Act (ARRA) and the associated funding came to an end. The program was restructured based on an understanding of the observations, attributed successes and identified shortfalls, and the consolidation of those lessons. Mentoring the application of proven methods for improving human performance was shown effective at increasing success in day-to-day activities and increasing confidence and level of skill of supervisors. While mentoring program effectiveness is difficult to

  2. Stochastic Models of Human Errors

    NASA Technical Reports Server (NTRS)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  3. Biological databases for human research.

    PubMed

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-02-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. PMID:25712261

  4. Biological Databases for Human Research

    PubMed Central

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-01-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. PMID:25712261

  5. Toxicities of trichosanthin and alpha-momorcharin, abortifacient proteins from Chinese medicinal plants, on cultured tumor cell lines.

    PubMed

    Tsao, S W; Ng, T B; Yeung, H W

    1990-01-01

    Trichosanthin and alpha-momorcharin are abortifacient proteins extracted from Chinese medicinal herbs. Study of their in vitro cytotoxicities showed that the two proteins selectively injured choriocarcinoma and melanoma cells. Hepatoma cells represented the most resistant cell line among the various cell lines investigated. Cytotoxicity profiles of trichosanthin and alpha-momorcharin differed from those of anti-cancer drugs which interfere with DNA metabolism such as cisplatin, methotrexate and 5-fluorouracil. Radioactive precursor incorporation studies suggested that the two abortifacient proteins inhibited cellular protein synthesis. The marked decrease in secretion of human chorionic gonadotrophin and progesterone by choriocarcinoma cells after treatment with the proteins could be attributed mainly to loss of cells. PMID:2175958

  6. Human-human cooperative task characteristics and motion analysis based on human visual and auditory senses

    NASA Astrophysics Data System (ADS)

    Abu Bakar, Shahriman; Ikeura, Ryojun; Handa, Yuichiro; Yano, Takemi; Mizutani, Kazuki

    2007-12-01

    To design human cooperative robot it is necessary to take into consideration the factor to make the robot move as smooth as possible during the cooperative task. This is to ensure that human can work with robot with high degree of smoothness that would ensure the task is completed without stress and fatigue to human. Since robot does not know the feeling of human, we need to replicate the human motion characteristic into the robot. In human-human cooperative task normally to achieve good cooperative task, human will use auditory, visual and touch senses. We want to understand what kind of sense at which moment it is uses to get good cooperative task. We arranged the experiment subjects so that they utilized their senses individually during the cooperative task. Experiment devices are equipped with 3D position sensors and force sensors to measure the position, angle and force value. This research is concentrating the force and torque characteristic that occurs to the human participants during human-to-human cooperative work where the human audio, visual and touch senses are applied.

  7. Antarctic skuas recognize individual humans.

    PubMed

    Lee, Won Young; Han, Yeong-Deok; Lee, Sang-Im; Jablonski, Piotr G; Jung, Jin-Woo; Kim, Jeong-Hoon

    2016-07-01

    Recent findings report that wild animals can recognize individual humans. To explain how the animals distinguish humans, two hypotheses are proposed. The high cognitive abilities hypothesis implies that pre-existing high intelligence enabled animals to acquire such abilities. The pre-exposure to stimuli hypothesis suggests that frequent encounters with humans promote the acquisition of discriminatory abilities in these species. Here, we examine individual human recognition abilities in a wild Antarctic species, the brown skua (Stercorarius antarcticus), which lives away from typical human settlements and was only recently exposed to humans due to activities at Antarctic stations. We found that, as nest visits were repeated, the skua parents responded at further distances and were more likely to attack the nest intruder. Also, we demonstrated that seven out of seven breeding pairs of skuas selectively responded to a human nest intruder with aggression and ignored a neutral human who had not previously approached the nest. The results indicate that Antarctic skuas, a species that typically inhabited in human-free areas, are able to recognize individual humans who disturbed their nests. Our findings generally support the high cognitive abilities hypothesis, but this ability can be acquired during a relatively short period in the life of an individual as a result of interactions between individual birds and humans. PMID:26939544

  8. Selection of Recombinant Human Antibodies.

    PubMed

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  9. Tactual interfaces: The human perceiver

    NASA Technical Reports Server (NTRS)

    Srinivasan, M. A.

    1991-01-01

    Increasingly complex human-machine interactions, such as in teleoperation or in virtual environments, have necessitated the optimal use of the human tactual channel for information transfer. This need leads to a demand for a basic understanding of how the human tactual system works, so that the tactual interface between the human and the machine can receive the command signals from the human, as well as display the information to the human, in a manner that appears natural to the human. The tactual information consists of two components: (1) contact information which specifies the nature of direct contact with the object; and (2) kinesthetic information which refers to the position and motion of the limbs. This paper is mostly concerned with contact information.

  10. Humanized Antibodies for Antiviral Therapy

    NASA Astrophysics Data System (ADS)

    Co, Man Sung; Deschamps, Marguerite; Whitley, Richard J.; Queen, Cary

    1991-04-01

    Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

  11. The Human Variome Project.

    PubMed

    Burn, John; Watson, Michael

    2016-06-01

    The practical realization of genomics has meant a growing realization that variant interpretation is a major barrier to practical use of DNA sequence data. The late Professor Dick Cotton devoted his life to innovation in molecular genetics and was a prime mover in the international response to the need to understand the "variome." His leadership resulted in the launch first of the Human Genetic Variation Society and then, in 2006, an international agreement to launch the Human Variome Project (HVP), aimed at data integration enabled by standards and infrastructure of the databases of variants being identified in families with a range of inherited disorders. The project attracted a network of affiliates across 81 countries and earned formal recognition by UNESCO, which now hosts its biennial meetings. It has also signed a Memorandum of Understanding with the World Health Organization. Future progress will depend on longer term secure funding and integration with the efforts of the genomics community where the rapid advances in sequencing technology have enabled variant capture on a previously unimaginable scale. Efforts are underway to integrate the efforts of HVP with those of the Global Alliance for Genomics and Health to provide a lasting legacy of Dick Cotton's vision. PMID:26987309

  12. First human Cerenkography

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello Enrico; Ferdeghini, Marco; Cavedon, Carlo; Zivelonghi, Emanuele; Calandrino, Riccardo; Fenzi, Alberto; Sbarbati, Andrea; Boschi, Federico

    2013-02-01

    Cerenkov luminescence imaging is an emerging optical preclinical modality based on the detection of Cerenkov radiation induced by beta particles when traveling though biological tissues with a velocity greater than the speed of light. We present the first human Cerenkography obtained by detecting Cerenkov radiation escaping the thyroid gland of a patient treated for hyperthyroidism. The Cerenkov light was detected using an electron multiplied charge coupled device and a conventional C-mount lens. The system set-up has been tested by using a slab of ex vivo tissue equal to a 1 cm slice of chicken breast in order to simulate optical photons attenuation. We then imaged for 2 min the head and neck region of a patient treated orally 24 h before with 550 MBq of I-131. Co-registration between photographic and Cerenkov images showed a good localization of the Cerenkov light within the thyroid region. In conclusion, we showed that it is possible to obtain a planar image of Cerenkov photons escaping from a human tissue. Cerenkography is a potential novel medical tool to image superficial organs of patients treated with beta minus radiopharmaceuticals and can be extended to the imaging of beta plus emitters.

  13. The human respiratory gate

    PubMed Central

    Eckberg, Dwain L

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this ‘respiratory gating’ is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R–R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R–R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms. PMID:12626671

  14. Predicting Human Cooperation

    PubMed Central

    Nay, John J.; Vorobeychik, Yevgeniy

    2016-01-01

    The Prisoner’s Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner’s Dilemma (defection), when played by both players, is mutually harmful. Repetition of the Prisoner’s Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner’s Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner’s Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. We demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation. PMID:27171417

  15. Human kin detection.

    PubMed

    Bressan, Paola; Kramer, Peter

    2015-01-01

    Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non-kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, 'neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large. PMID:26263231

  16. SARSCEST (human factors)

    NASA Technical Reports Server (NTRS)

    Parsons, H. Mcilvaine

    1988-01-01

    People interact with the processes and products of contemporary technology. Individuals are affected by these in various ways and individuals shape them. Such interactions come under the label 'human factors'. To expand the understanding of those to whom the term is relatively unfamiliar, its domain includes both an applied science and applications of knowledge. It means both research and development, with implications of research both for basic science and for development. It encompasses not only design and testing but also training and personnel requirements, even though some unwisely try to split these apart both by name and institutionally. The territory includes more than performance at work, though concentration on that aspect, epitomized in the derivation of the term ergonomics, has overshadowed human factors interest in interactions between technology and the home, health, safety, consumers, children and later life, the handicapped, sports and recreation education, and travel. Two aspects of technology considered most significant for work performance, systems and automation, and several approaches to these, are discussed.

  17. The human respiratory gate

    NASA Technical Reports Server (NTRS)

    Eckberg, Dwain L.

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

  18. Predicting Human Cooperation.

    PubMed

    Nay, John J; Vorobeychik, Yevgeniy

    2016-01-01

    The Prisoner's Dilemma has been a subject of extensive research due to its importance in understanding the ever-present tension between individual self-interest and social benefit. A strictly dominant strategy in a Prisoner's Dilemma (defection), when played by both players, is mutually harmful. Repetition of the Prisoner's Dilemma can give rise to cooperation as an equilibrium, but defection is as well, and this ambiguity is difficult to resolve. The numerous behavioral experiments investigating the Prisoner's Dilemma highlight that players often cooperate, but the level of cooperation varies significantly with the specifics of the experimental predicament. We present the first computational model of human behavior in repeated Prisoner's Dilemma games that unifies the diversity of experimental observations in a systematic and quantitatively reliable manner. Our model relies on data we integrated from many experiments, comprising 168,386 individual decisions. The model is composed of two pieces: the first predicts the first-period action using solely the structural game parameters, while the second predicts dynamic actions using both game parameters and history of play. Our model is successful not merely at fitting the data, but in predicting behavior at multiple scales in experimental designs not used for calibration, using only information about the game structure. We demonstrate the power of our approach through a simulation analysis revealing how to best promote human cooperation. PMID:27171417

  19. Adipokines in human reproduction.

    PubMed

    Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

    2015-10-01

    Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age. PMID:26574894

  20. Lakeland Habitat for Humanity

    SciTech Connect

    Gilbride, Theresa L.

    2009-03-30

    This is a case study of the Lakeland, FLorida, Habitat for Humanity affiliate, which has partnered with DOE's Building America program to homes that achieve energy savings of 30% or more over the Building America baseline home (a home built to the 1993 Model Energy Code). The article includes a description of the energy-efficiency features used. The Lakeland affiliate built several of its homes with ducts in conditioned space, which minimizes heat losses and gains. They also used high-efficiency SEER 14 air conditioners; radiant barriers in the roof to keep attics cooler; above-code high-performance dual-pane vinyl-framed low-emissivity windows; a passive fresh air duct to the air handler; and duct blaster and blower door testing of every home to ensure the home's air tightness. This case study was also prepared as a flier titled "High Performance Builder Spotlight: Lakeland Habitat for Humanity, Lakeland, Florida,: which was cleared as PNNL-SA-59068 and distributed at the International Builders’ Show Feb 13-16, 2008, in Orlando, Florida.