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Sample records for human transcobalamin ii

  1. Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion.

    Science.gov (United States)

    Hashemi, Mohammad; Mokhtari, Mojgan; Yazdani-Shahrbabaki, Vajiheh; Danesh, Hiva; Bizhani, Fatemeh; Taheri, Mohsen

    2018-03-14

    It has been proposed that transcobalamin 2 (TCN2) and the transcobalamin 2 receptor (TCN2R) are associated with idiopathic recurrent spontaneous abortion (RSA). The aim of the present study was to investigate the impact of TCN2 rs1801198 and TCN2R rs2336573 polymorphism on RSA in a sample of Iranian population. This case-control study was done on 92 RSA patients and 93 normal, fertile women. Genotyping of the TCN2 rs1801198 and TCN2R rs2336573 variants was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The findings showed no significant association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk/protection of RSA. Our results did not support an association between the TCN2 polymorphism and the risk of RSA in a sample of southeast Iranian population. Larger studies with different ethnicities are needed to evaluate the possible impact of TCN2 and TCN2R polymorphisms on the pathogenesis of RSA. Impact statement What is already known on this subject? Recurrent spontaneous abortion (RSA), a multifactorial condition, is one of the most common complications of pregnancy. It has been proposed that genetic polymorphisms play a role in the pathogenesis of RSA. Few studies have examined the association between TNC2 and TCN2R polymorphisms and the RSA risk and the findings were inconsistent. The aim of the current study was to determine the possible association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the RSA in a sample of the southeast Iranian population. What do the results of the study add? The findings of the present case-control study did not support an association between the TCN2 rs1801198 and TCN2R rs2336573 polymorphisms and the risk of RSA in a sample of the Iranian population. What are the implications of these findings for clinical practice and future research? The findings of this study may provide a basis for future studies with larger sample sizes and different ethnicities

  2. Validity of transcobalamin II-based radioassay for the determination of serum vitamin B12 concentrations

    International Nuclear Information System (INIS)

    Paltridge, G.; Rudzki, Z.; Ryall, R.G.

    1980-01-01

    A valid radioassay for the estimation of serum vitamin B 12 in the presence of naturally occurring vitamin B 12 (= cobalamin) analogues can be operated if serum transcobalamin II (TC II) is used as the binding protein. Serum samples that gave diagnostically discrepant results when their vitamin B 12 content was analysed (i) by a commercial radioassay known to be susceptible to interference from cobalamin analogues, and (ii) by microbiological assay, were further analysed by an alternative radioassay which uses the transcobalamins (principally TC II) of diluted normal serum as the assay binding protein. Concordance between the results from microbiological assay and the TC II-based radioassay was found in all cases. In an extended study over a three-year period, all routine serum samples sent for vitamin B 12 analysis that had a vitamin B 12 content of less than 320 ng/l by the TC II-based radioassay (reference range 200-850 ng/l) were reanalysed using an established microbiological method. Over 1000 samples were thus analysed. The data are presented to demonstrate the validity of the TC II-based radioassay results in this group of patients, serum samples from which are most likely to produce diagnostically erroneous vitamin B 12 results when analysed by a radioassay that is less specific for cobalamins. (author)

  3. Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications

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    Zetterberg Henrik

    2004-02-01

    Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.

  4. A soluble form of the transcobalamin receptor CD320 can be detected in human serum

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Berg; Quadros, Edward V.; Christensen, Anna Lisa

    2010-01-01

    Background: Recently, the cell-surface receptor involved in the internalisation of the cobalamin(vitamin B12, Cbl) transporting protein, transcobalamin(TC), was described, and was found to be CD320(1). So far, it remains unsolved whether CD320 is present in a soluble form (sCD320) in serum. Our aim...

  5. Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)

    DEFF Research Database (Denmark)

    Hoffmann-Lücke, Elke; Arendt, Johan F B; Nissen, Peter H

    2013-01-01

    deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both...... transcobalamin and part of sCD320. CONCLUSIONS: The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation....

  6. Seven Patients With Transcobalamin Deficiency Diagnosed Between 2010 and 2014

    DEFF Research Database (Denmark)

    Yildirim, Zuhal K; Nexo, Ebba; Rupar, Tony

    2017-01-01

    Transcobalamin deficiency (OMIM 275350) is a rare autosomal recessive disease presenting with nonspecific clinical features in early infancy. We report the clinical and laboratory manifestations of 7 children diagnosed with transcobalamin deficiency. All patients were admitted between 2 and 4 mon....... In conclusion, 1 mg of intramuscular CN-Cbl every week suffices for hematological improvement but not for normal neurological development in patients who all had relapse due to decrease or cessation of treatment....

  7. First trimester serum levels of the soluble transcobalamin receptor, holo-transcobalamin, and total transcobalamin in relation to preeclampsia risk

    DEFF Research Database (Denmark)

    Abuyaman, Omar; Torring, Niels; Obeid, Rima

    2016-01-01

    transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy. STUDY DESIGN...... preeclampsia while the controls remained normotensive throughout pregnancy. We measured the serum concentration of sCD320, holoTC, and total TC by using in-house ELISA methods. RESULTS: First trimester median concentrations of sCD320, holoTC and total TC were not significantly different between cases...... and controls. The odd ratio for developing preeclampsia based on exposure to low or high levels of sCD320, holoTC or total TC at first trimester was not significant. The reference intervals (2.5-97.5% percentiles (median)) derived from the controls were 50-170 (90) pmol\\L for sCD320, 20-140 (70) pmol...

  8. Enzymatic extraction of cobalamin from monoclonal antibody captured haptocorrin and transcobalamin

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Mørkbak, Anne Louise; Nexo, Ebba

    2007-01-01

    OBJECTIVES: Current extraction methods for cobalamins from serum influence the molecular characteristics of the vitamin. Therefore, an extraction procedure that leaves the cobalamins unchanged is needed. DESIGN AND METHODS: Monoclonal antibodies towards transcobalamin (TC) and haptocorrin (HC) (in...

  9. Characterization of a monoclonal antibody with specificity for holo-transcobalamin

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    Fedosov Sergey N

    2006-01-01

    Full Text Available Abstract Background Holotranscobalamin, cobalamin-saturated transcobalamin, is the minor fraction of circulating cobalamin (vitamin B12, which is available for cellular uptake and hence is physiologically relevant. Currently, no method allows simple, direct quantification of holotranscobalamin. We now report on the identification and characterization of a monoclonal antibody with a unique specificity for holotranscobalamin. Methods The specificity and affinity of the monoclonal antibodies were determined using surface plasmon resonance and recombinant transcobalamin as well as by immobilizing the antibodies on magnetic microspheres and using native transcobalamin in serum. The epitope of the holotranscobalamin specific antibody was identified using phage display and comparison to a de novo generated three-dimensional model of transcobalamin using the program Rosetta. A direct assay for holotrnscobalamin in the ELISA format was developed using the specific antibody and compared to the commercial assay HoloTC RIA. Results An antibody exhibiting >100-fold specificity for holotranscobalamin over apotranscobalamin was identified. The affinity but not the specificity varied inversely with ionic strength and pH, indicating importance of electrostatic interactions. The epitope was discontinuous and epitope mapping of the antibody by phage display identified two similar motifs with no direct sequence similarity to transcobalamin. A comparison of the motifs with a de novo generated three-dimensional model of transcobalamin identified two structures in the N-terminal part of transcobalamin that resembled the motif. Using this antibody an ELISA based prototype assay was developed and compared to the only available commercial assay for measuring holotranscobalamin, HoloTC RIA. Conclusion The identified antibody possesses a unique specificity for holotranscobalamin and can be used to develop a direct assay for the quantification of holotranscobalamin.

  10. The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates to dementia-related biomarkers tau proteins and amyloid-beta

    DEFF Research Database (Denmark)

    Abuyaman, Omar; Nexo, Ebba

    2015-01-01

    BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320. Recently, we identified a soluble form of CD320 (sCD320) in human plasma. Here we present data on the occurrence of this soluble receptor...... phospho-tau (181P) (p-tau), total tau (t-tau) and amyloid-beta 1-42 (Aβ) (n = 177) employing commercial ELISA kits (Innogenetics Company). Size exclusion chromatography was performed on a Superdex 200 column. RESULTS: The median sCD320 concentration in CSF (14 pmol/L) is around five times lower than...

  11. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older hispanics

    Science.gov (United States)

    Background: A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. Methods: TC genotype and its associations with i...

  12. Transcobalamin 776C-->G polymorphism is associated with peripheral neuropathy in elderly with high folate intake

    Science.gov (United States)

    Background: The 776C-->G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is ade...

  13. Transcobalamin from cow milk: isolation and physico-chemical properties

    DEFF Research Database (Denmark)

    Fedosov, Sergey; Petersen, Torben Ellebæk; Nexø, Ebba

    1996-01-01

    The concentration of endogenous cobalamin (Cbl) in cow milk was 3.3 nM while the Cbl-binding capacity was 0.05 nM. Both endogenous and newly added Cbl showed similar quantitative distribution between a 280 kDa protein complex (45%) and a 43 kDa Cbl-binder (55%). Long time incubation, as well...... as urea treatment, was accompanied by a slow release of the 43 kDa Cbl-binder from the 280 kDa fraction. No other Cbl-binding proteins appeared after these procedures. The 43 kDa binder from cow milk, depleted of the ligand by urea treatment, reacted with Cbl even in the presence of a B12 analogue...... was significantly suppressed at pH 2.0. The N-terminal sequence of the purified 43 kDa Cbl-binder revealed homology with TC from human and rabbit plasma. In conclusion we have shown that TC is the main Cbl-binding protein in cow milk. This is surprising, since previous studies on human and rat milk have shown...

  14. The soluble transcobalamin receptor (sCD320) in relation to Alzheimer's disease and cognitive scores

    DEFF Research Database (Denmark)

    Abuyaman, Omar; Combrinck, Marc; Smith, A David

    2017-01-01

    The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates with the dementia-related biomarkers phospho-tau and total-tau. Here we present data on the relation of sCD320 to Alzheimer's disease and scores of cognitive tests. Lumbar cerebrospinal fluid samples from...... 42 pathologically-confirmed cases of Alzheimer's disease and 25 non-demented controls were analyzed for sCD320 employing an in-house ELISA. The participants' cognitive functions were tested using the Cambridge Cognition Examination (CAMCOG) and the Mini-Mental State Examination (MMSE...... be employed as a biomarker for differentiating Alzheimer dementia patients from controls. Further studies are warranted to explore the non-linear correlations between sCD320 and scores of cognitive function....

  15. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    Science.gov (United States)

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  16. Holo-transcobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status

    DEFF Research Database (Denmark)

    von Castel-Roberts, Kristina M; Mørkbak, Anne Louise; Nexo, Ebba

    2007-01-01

    BACKGROUND: It has been hypothesized that the response of holo-transcobalamin (holo-TC) to oral vitamin B-12 may be used to assess absorption. To develop a reliable clinical absorption test that uses holo-TC, it is necessary to determine the optimal timeline for vitamin B-12 administration...... and postdose assessment. OBJECTIVE: The objective of this study was to assess the magnitude and patterns of change in the postabsorption response of holo-TC to oral vitamin B-12. DESIGN: Adult (18-49 y) male and female participants (n = 21) with normal vitamin B-12 status were given three 9-mug doses...... of vitamin B-12 at 6-h intervals beginning early morning (baseline) on day 1. Blood was drawn at 17 timed intervals over the course of 3 d for the analysis of holo-TC and other indicators of vitamin B-12 status. RESULTS: Mean holo-TC increased significantly (P

  17. Eco RI RFLP in the human IGF II gene

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, S; Garofalo, S; Robledo, R; Monticelli, A; Conti, A; Chiarotti, L; Frunzio, R; Bruni, C B; Varrone, S

    1988-03-25

    The probe was a 500 bp cDNA containing exons 2-3 and 4 of the human IGF II gene. The clone was isolated by screening a human liver cDNA library with synthetic oligonucleotides. Eco RI digestion of genomic DNA and hybridization with the IGF II probe detects a two allele polymorphism with allelic fragments of 13.5 kb and 10.5 kb. The frequency was studied 38 unrelated Caucasians: Human IGF II gene was localized on the short arm of chromosome 11 (p15) by in situ hybridization. Codominant segregation was observed in 2 Caucasian families (10 individuals).

  18. IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells

    International Nuclear Information System (INIS)

    Sinha, M.K.; Buchanan, C.; Raineri-Maldonado, C.; Khazanie, P.; Atkinson, S.; DiMarchi, R.; Caro, J.F.

    1990-01-01

    Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: (1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; (2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; (3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and (4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin

  19. The World War II Era and Human Rights Education

    Science.gov (United States)

    Waters, Stewart; Russell, William B., III

    2012-01-01

    International revulsion at the violation of human rights during World War II helped spark a global movement to define and protect individual human rights. Starting with the creation of war crimes tribunals after the war, this newfound awareness stimulated a concerted international effort to establish human rights for all, both in periods of war…

  20. Reproduction (II): Human Control of Reproductive Processes

    Science.gov (United States)

    Jost, Alfred

    1970-01-01

    Describes methods of intervening in reproduction of animals and humans (artificial insemination, contraception, ovular and blastodisc transplants, pre selection of sex, cloning) and discusses the social implications of their use with humans. (AL)

  1. Angiotensin II attenuates the natriuresis of water immersion in humans

    DEFF Research Database (Denmark)

    Schou, Morten; Gabrielsen, Anders; Bruun, Niels Eske

    2002-01-01

    The hypothesis was tested that suppression of generation of ANG II is one of the mechanisms of the water immersion (WI)-induced natriuresis in humans. In one protocol, eight healthy young males were subjected to 3 h of 1) WI (WI + placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). min...

  2. Vitamin B12-impaired metabolism produces apoptosis and Parkinson phenotype in rats expressing the transcobalamin-oleosin chimera in substantia nigra.

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    Carlos Enrique Orozco-Barrios

    Full Text Available BACKGROUND: Vitamin B12 is indispensable for proper brain functioning and cytosolic synthesis of S-adenosylmethionine. Whether its deficiency produces effects on viability and apoptosis of neurons remains unknown. There is a particular interest in investigating these effects in Parkinson disease where Levodopa treatment is known to increase the consumption of S-adenosylmethionine. To cause deprivation of vitamin B12, we have recently developed a cell model that produces decreased synthesis of S-adenosylmethionine by anchoring transcobalamin (TCII to the reticulum through its fusion with Oleosin (OLEO. METHODOLOGY: Gene constructs including transcobalamin-oleosin (TCII-OLEO and control constructs, green fluorescent protein-transcobalamin-oleosin (GFP-TCII-OLEO, oleosin-transcobalamin (OLEO-TCII, TCII and OLEO were used for expression in N1E-115 cells (mouse neuroblastoma and in substantia nigra of adult rats, using a targeted transfection with a Neurotensin polyplex system. We studied the viability and the apoptosis in the transfected cells and targeted tissue. The turning behavior was evaluated in the rats transfected with the different plasmids. PRINCIPAL FINDINGS: The transfection of N1E-115 cells by the TCII-OLEO-expressing plasmid significantly affected cell viability and increased immunoreactivity of cleaved Caspase-3. No change in propidium iodide uptake (used as a necrosis marker was observed. The transfected rats lost neurons immunoreactive to tyrosine hydroxylase. The expression of TCII-OLEO was observed in cells immunoreactive to tyrosine hydroxylase of the substantia nigra, with a superimposed expression of cleaved Caspase-3. These cellular and tissular effects were not observed with the control plasmids. Rats transfected with TCII-OLEO expressing plasmid presented with a significantly higher number of turns, compared with those transfected with the other plasmids. CONCLUSIONS/SIGNIFICANCE: In conclusion, the TCII-OLEO transfection

  3. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  4. Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

    Science.gov (United States)

    Ranjbar, Samira; Ghobadi, Sirous; Khodarahmi, Reza; Nemati, Houshang

    2012-05-01

    This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  6. Molecular cloning of the human casein kinase II α subunit

    International Nuclear Information System (INIS)

    Meisner, H.; Heller-Harrison, R.; Buxton, J.; Czech, M.P.

    1989-01-01

    A human cDNA encoding the α subunit of casein kinase II and a partial cDNA encoding the rat homologue were isolated by using a Drosophila casein kinase II cDNA probe. The 2.2-kb human cDNA contains a 1.2-kb open reading frame, 150 nucleotides of 5' leader, and 850 nucleotides of 3' noncoding region. Except for the first 7 deduced amino acids that are missing in the rat cDNA, the 328 amino acids beginning with the amino terminus are identical between human and rat. The Drosophila enzyme sequence is 90% identical with the human casein kinase II sequence, and there is only a single amino acid difference between the published partial bovine sequence and the human sequence. In addition, the C-terminus of the human cDNA has an extra 53 amino acids not present in Drosophila. Northern analysis of rat and human RNA showed predominant bands of 5.5, 3.1, and 1.8 kb. In rat tissues, brain and spleen had the highest levels of casein kinase II α subunit specific RNA, while skeletal muscle showed the lowest. Southern analysis of human cultured cell and tissue genomic DNA using the full-length cDNA probe revealed two bands with restriction enzymes that have no recognition sites within the cDNA and three to six bands with enzymes having single internal sites. These results are consistent with the possibility that two genes encode the α subunits

  7. Oxidative Metabolites of Curcumin Poison Human Type II Topoisomerases†

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    Ketron, Adam C.; Gordon, Odaine N.; Schneider, Claus; Osheroff, Neil

    2013-01-01

    The polyphenol curcumin is the principal flavor and color component of the spice turmeric. Beyond its culinary uses, curcumin is believed to positively impact human health and displays antioxidant, anti-inflammatory, antibacterial, and chemopreventive properties. It also is in clinical trials as an anticancer agent. In aqueous solution at physiological pH, curcumin undergoes spontaneous autoxidation that is enhanced by oxidizing agents. The reaction proceeds through a series of quinone methide and other reactive intermediates to form a final dioxygenated bicyclopentadione product. Several naturally occurring polyphenols that can form quinones have been shown to act as topoisomerase II poisons (i.e., increase levels of topoisomerase II-mediated DNA cleavage). Because several of these compounds have chemopreventive properties, we determined the effects of curcumin, its oxidative metabolites, and structurally related degradation products (vanillin, ferulic acid, and feruloylmethane), on the DNA cleavage activities of human topoisomerase IIα and IIβ. Intermediates in the curcumin oxidation pathway increased DNA scission mediated by both enzymes ~4-5–fold. In contrast, curcumin and the bicyclopentadione, as well as vanillin, ferulic acid, and feruloylmethane, had no effect on DNA cleavage. As found for other quinone-based compounds, curcumin oxidation intermediates acted as redox-dependent (as opposed to interfacial) topoisomerase II poisons. Finally, under conditions that promote oxidation, the dietary spice turmeric enhanced topoisomerase II-mediated DNA cleavage. Thus, even within the more complex spice formulation, oxidized curcumin intermediates appear to function as topoisomerase II poisons. PMID:23253398

  8. BcII RFLP for the human vimentin gene

    Energy Technology Data Exchange (ETDEWEB)

    Marcus, E M; Smith, B A; Telenius, H; Ponder, B A.J.; Mathew, C G.P. [Haddow Laboratories, Surrey (England); Landsvater, R M; Buys, C H.C.M. [State Univ. of Groningen (Netherlands); Ferrari, S [Temple University Medical School, Philadelphia, PA (USA)

    1988-09-26

    A 1.1 kb cDNA clone (hp4F1) encoding the human vimentin gene was identified in a human library by screening with 4F1, a hamster vimentin cDNA. BcII (TGATCA) recognizes a two allele polymorphism: bands A1 at 8.1 kb, and A2 at 3.6 kb. The allele frequency was determined in 47 unrelated Caucasian individuals. The RFLP was mapped to chromosome 10pter-10q23 using somatic cell hybrids and to 10p13 by in situ hybridization. Co-dominant segregation was observed in 2 informative families.

  9. The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation

    DEFF Research Database (Denmark)

    Charni-Ben Tabassi, N; Desmarais, S; Jensen, Anne-Christine Bay

    2008-01-01

    human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage....... Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA...

  10. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each ...

  11. Blood-group-Ii-active gangliosides of human erythrocyte membranes

    International Nuclear Information System (INIS)

    Feizi, T.; Childs, R.A.; Hakomori, S.-I.; Powell, M.E.

    1978-01-01

    More than ten new types of gangliosides, in addition to haematoside and sialosylparagloboside, were isolated from human erythrocyte membranes. These were separated by successive chromatographies on DAEA-Sephadex, on porous silica-gel columns and on thin-layer silica gel as acetylated compounds. Highly potent blood-group-Ii and moderate blood-group-H activities were demonstrated in some of the ganglioside fractions. The gangliosides incorporated into chlolesterol/phosphatidylcholine liposomes stoicheiometrically inhibited binding of anti-(blood-group-I and i) antibodies to a radioiodinated blood-group-Ii-active glycoprotein. The fraction with the highest blood-group-I activity, I(g) fraction, behaved like sialosyl-deca- to dodeca-glycosylceramides on t.l.c. Certain blood-group-I and most of the i-determinants were in partially or completely cryptic form and could be unmasked by sialidase treatment. Thus the I and i antigens, which are known to occur on internal structures of blood-group-ABH-active glycoproteins in secretions, also occur in the interior of the carbohydrate chains of erythrocyte gangliosides. (author)

  12. DNA structure in human RNA polymerase II promoters

    DEFF Research Database (Denmark)

    Pedersen, Anders Gorm; Baldi, Pierre; Chauvin, Yves

    1998-01-01

    with a very low level of sequence similarity. The sequences, which include both TATA-containing and TATA-less promoters, are aligned by hidden Markov models. Using three different models of sequence-derived DNA bendability, the aligned promoters display a common structural profile with bendability being low...... protein in a manner reminiscent of DNA in a nucleosome. This notion is further supported by the finding that the periodic bendability is caused mainly by the complementary triplet pairs CAG/CTG and GGC/GCC, which previously have been found to correlate with nucleosome positioning. We present models where......The fact that DNA three-dimensional structure is important for transcriptional regulation begs the question of whether eukaryotic promoters contain general structural features independently of what genes they control. We present an analysis of a large set of human RNA polymerase II promoters...

  13. Dual pathway for angiotensin II formation in human internal mammary arteries

    NARCIS (Netherlands)

    Voors, A. A.; Pinto, Y. M.; Buikema, H.; Urata, H.; Oosterga, M.; Rooks, G.; Grandjean, J. G.; Ganten, D.; van Gilst, W. H.

    1998-01-01

    1. Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convert antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin II formation was due to another enzyme, identified as human heart chymase. In the human

  14. MHC class II molecules regulate growth in human T cells

    DEFF Research Database (Denmark)

    Nielsen, M; Odum, Niels; Bendtzen, K

    1994-01-01

    MHC-class-II-positive T cells are found in tissues involved in autoimmune disorders. Stimulation of class II molecules by monoclonal antibodies (mAbs) or bacterial superantigens induces protein tyrosine phosphorylation through activation of protein tyrosine kinases in T cells, and class II signals...... lines tested. Only one of three CD4+, CD45RAhigh, ROhigh T cells responded to class II costimulation. There was no correlation between T cell responsiveness to class II and the cytokine production profile of the T cell in question. Thus, T cell lines producing interferon (IFN)-gamma but not IL-4 (TH1...... modulate several T cell responses. Here, we studied further the role of class II molecules in the regulation of T cell growth. Costimulation of class II molecules by immobilized HLA-DR mAb significantly enhanced interleukin (IL)-2-supported T cell growth of the majority of CD4+, CD45RAlow, ROhigh T cell...

  15. Fragment Screening of Human Kynurenine Aminotransferase-II.

    Science.gov (United States)

    Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret

    2018-03-01

    Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.

  16. Dual pathway for angiotensin II formation in human internal mammary arteries

    NARCIS (Netherlands)

    Voors, AA; Pinto, YM; Buikema, H; Urata, H; Oosterga, M; Roos, G; Grandjean, JG; Ganten, D; van Gilst, WH

    1 Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convect antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin ZI formation was due to another enzyme, identified as human heart chymase. In the human

  17. Regulated gene expression in cultured type II cells of adult human lung

    OpenAIRE

    Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

    2010-01-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

  18. Cloning and expression of a novel human profilin variant, profilin II

    DEFF Research Database (Denmark)

    Honoré, B; Madsen, Peder; Andersen, A H

    1993-01-01

    We have isolated a 1.7 kbp cDNA encoding a 140 amino acid protein (15.1 kDa, pI 5.91) with a high sequence similarity (62%) to human profilin (profilin I). We have termed this variant profilin II. Northern blot analysis showed that profilin II is highly expressed in brain, skeletal muscle and kid...

  19. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used ... intensive search for novel drugs is ongoing, through synthesis of new ..... License (http://creativecommons.org/licenses/by/. 4.0) and the ...

  20. Identification and characterization of the human type II collagen gene (COL2A1).

    OpenAIRE

    Cheah, Kathryn; Stoker, N.G.; Griffin, J.R.; Grosveld, Frank; Solomon, E.

    1985-01-01

    textabstractThe gene contained in the human cosmid clone CosHcol1, previously designated an alpha 1(I) collagen-like gene, has now been identified. CosHcol1 hybridizes strongly to a single 5.9-kilobase mRNA species present only in tissue in which type II collagen is expressed. DNA sequence analysis shows that this clone is highly homologous to the chicken alpha 1(II) collagen gene. These data together suggest that CosHcol1 contains the human alpha 1(II) collagen gene COL2A1. The clone appears...

  1. Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Yoon Jin Cho

    2016-09-01

    Full Text Available Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

  2. Detection and quantitation of glutamate carboxypeptidase II in human blood

    Czech Academy of Sciences Publication Activity Database

    Knedlík, Tomáš; Navrátil, Václav; Vik, V.; Pacík, D.; Šácha, Pavel; Konvalinka, Jan

    2014-01-01

    Roč. 74, č. 7 (2014), s. 768-780 ISSN 0270-4137 R&D Projects: GA ČR GAP304/12/0847 Grant - others:OPPC(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : serum marker * glutamate carboxypeptidase II * plasma glutamate carboxypeptidase * prostate cancer * prostate -specific membrane antigen Subject RIV: CE - Biochemistry Impact factor: 3.565, year: 2014

  3. Noncooperative cadmium(II) binding to human metallothionein 1a

    International Nuclear Information System (INIS)

    Sutherland, Duncan E.K.; Stillman, Martin J.

    2008-01-01

    The two-domain (βα) mammalian metallothionein binds seven divalent metals, however, the binding mechanism is not well characterized and recent reports require the presence of the partially metallated protein. In this paper, step-wise metallation of the metal-free, two-domain βα-rhMT and the isolated β-rhMT using Cd(II) is shown to proceed in a noncooperative manner by analysis of electrospray ionization mass spectrometric data. Under limiting amounts of Cd(II), all intermediate metallation states up to the fully metallated Cd 3 -β-rhMT and Cd 7 -βα-rhMT were observed. Addition of excess Cd(II), resulted in formation of the supermetallated (metallation in excess of normal levels) Cd 4 -β- and Cd 8 -βα-metallothionein species. These data establish that noncooperative cadmium metallation is a property of each isolated domain and the complete two-domain protein. Our data now also establish that supermetallation is a property that may provide information about the mechanism of metal transfer to other proteins

  4. Insulin-like growth factor II (IGF II) in human brain: regional distribution of IGF II and of higher molecular mass forms

    International Nuclear Information System (INIS)

    Haselbacher, G.K.; Schwab, M.E.; Pasi, A.; Humbel, R.E.

    1985-01-01

    Twenty-four distinct areas of human brain were analyzed for the presence of insulin-like growth factor (IGF). As reported for cerebrospinal fluid, only IGF II-like immunoreactivity, but no significant amounts of IGF I-like immunoreactivity, could be found. Upon gel permeation chromatography, two to five distinct size classes were separated on the basis of their immunoreactivity. Radioimmunoassays and a bioassay also gave results indistinguishable from those of serum IGF II. The highest amounts of IGF II-like immunoreactivity occur in the anterior pituitary. This is up to 100 times more than in most other brain regions analyzed. The higher molecular mass immunoreactive species were partially characterized. After immunoaffinity purification, the 38- and 26-kDa species are active in a bioassay. Specific IGF-binding protein activity could be shown after purification of the 38- and 26-kDa species on an IGF-affinity column. The 13-kDa species released significant amounts of 7.5-kDa material. The results are interpreted as evidence for the presence of IGF II synthesized locally in human brain

  5. Investigation of the proteins relaxation time in human blood serum; Badania relaksacyjne bialek surowicy krwi II

    Energy Technology Data Exchange (ETDEWEB)

    Blicharska, B.; Klauza, M. [Inst. Fizyki, Uniwersytet Jagiellonski, Cracow (Poland); Kuliszkiewicz-Janus, M. [Akademia Medyczna, Wroclaw (Poland)

    1994-12-31

    In this paper the results of human blood serum proteins relaxation time measurements by means of NMR method are presented. The measurements have been done for three samples of human blood: i/laudably ii/leukemia iii/granulomas. The dependences of the relaxation time on the temperature are also presented. 3 refs, 4 figs.

  6. Development of human factors design review guidelines(II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 11 refs., 2 figs., 2 tabs.

  7. Development of human factors design review guidelines(II)

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994

  8. Example of human individual identification from World War II gravesite.

    Science.gov (United States)

    Ossowski, Andrzej; Kuś, Marta; Brzeziński, Piotr; Prüffer, Jakub; Piątek, Jarosław; Zielińska, Grażyna; Bykowska, Milena; Jałowińska, Katarzyna; Torgaszev, Anton; Skoryukov, Antoliy; Parafiniuk, Mirosław

    2013-12-10

    This paper presents the procedure elaborated by our team which was applied to the mode of identification of Red Army soldiers who were taken as prisoners by the German Army during World War II and deceased in captivity. In the course of our search the unmarked burial of ten Soviet prisoners of war was found. Historical, anthropological and genetic research conducted by us led to the personal identification of nine of them, including two by means of DNA analysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns

    International Nuclear Information System (INIS)

    Altman, R.; Harrich, D.; Garcia, J.A.; Gaynor, R.B.

    1988-01-01

    Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses

  10. Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody

    International Nuclear Information System (INIS)

    Nakamura, Kayoko; Kubo, Atsushi; Hashimoto, Shozo; Furuuchi, Takayuki; Abe, Osahiko; Takami, Hiroshi.

    1988-01-01

    The potential of DU-PAN II, monoclonal antibody (IgM), which was raised against the human tumor cell line, was evaluated for radioimmunodetection of human pancreatic tumors (PAN-5-JCK and EXP-58) grown in nude mice. 125 I-labeled DU-PAN II was accumulated into PAN-5-JCK producing DU-PAN II antigen with a tumor-to-blood ratio of 2.72 ± 3.00, but it did not localize in EXP-58 because of insufficient DU-PAN II. There was no significant uptake of 125 I-nonimmunized IgM in PAN-5-JCK. These facts indicated the specific tumor uptake of DU-PAN II. Excellent images of the tumor PAN-5-JCK were obtained 3 days after the injection of 125 I-DU-PAN II. Gel chromatography was also investigated with respect to the plasma taken from mice injected with antibody, or incubated with antibody in vitro. The results indicate that circulating antigen affected the tumor uptake of DU-PAN II: The more the tumor grew, the higher the amount of antigen excreted into the blood, leading to the degradation of DU-PAN II before it reached the tumor sites. Consequently, the immunoscintigram of the small tumor was remarkably clear. The catabolism and the radiolysis of the labeled IgM injected are critical points in applying immunoscintigraphy. (author)

  11. [Bartonellosis. II. Other Bartonella responsible for human diseases].

    Science.gov (United States)

    Piémont, Y; Heller, R

    1999-01-01

    In addition to Bartonella henselae, five other Bartonella species were involved in human pathology. As for B. henselae, ectoparasites seem to be responsible for the transmission of most or all these bacterial species. B. bacilliformis is responsible for Carrion's disease that occurs in some valleys of Colombia, Ecuador and Peru. This disease is transmitted by biting of infected sandflies. The bacterial reservoir is constituted by humans only. That disease occurs either as an acute form with severe infectious hemolytic anemia (or Oroya fever), or as benign cutaneous tumors, also called verruga peruana. Healthy blood carriers of the bacterium exist. Trench fever was described during the First World War. This non-lethal disease is constituted of recurrent febrile attacks associated particularly with osseous pains. The causative agent of the disease is B. quintana, transmitted by the body louse. Humans seem to be the reservoir of that bacterium. In some patients, B. quintana can be responsible for endocarditis, bacillary angiomatosis and chronic or recurrent bacteremia. Other human infections due to Bartonella sp. have been described: B. vinsonii, isolated from blood of small rodents, and B. elizabethae, the reservoir of which is currently unknown, can be responsible for endocardites. B. clarridgeiae (isolated from blood of 5% of pet cats and 17% of stray cats) may be responsible for human cat scratch disease. All these bartonelloses are diagnosed by non-standard blood culture or by in vitro DNA amplification or by serological testing. Their treatment requires tetracyclines or chloramphenicol or macrolides.

  12. Cholinergic neurotransmission in human corpus cavernosum. II. Acetylcholine synthesis

    International Nuclear Information System (INIS)

    Blanco, R.; De Tejada, S.; Goldstein, I.; Krane, R.J.; Wotiz, H.H.; Cohen, R.A.

    1988-01-01

    Physiological and histochemical evidence indicates that cholinergic nerves may participate in mediating penile erection. Acetylcholine synthesis and release was studied in isolated human corporal tissue. Human corpus cavernosum incubated with [ 3 H]choline accumulated [ 3 H]choline and synthesized [ 3 H]acethylcholine in an concentration-dependent manner. [ 3 H]Acetylcholine accumulation by the tissue was inhibited by hemicholinium-3, a specific antagonist of the high-affinity choline transport in cholinergic nerves. Transmural electrical field stimulation caused release of [ 3 H]acetylcholine which was significantly diminished by inhibiting neurotransmission with calcium-free physiological salt solution or tetrodotoxin. These observations provide biochemical and physiological evidence for the existence of cholinergic innervation in human corpus cavernosum

  13. Introduction: Radical Teaching About Human Rights Part II

    Directory of Open Access Journals (Sweden)

    Michael Bennett

    2016-02-01

    Full Text Available In our introduction to the first of these two issues of Radical Teacher devoted to “Radical Teaching About Human Rights,” we cautioned that all forms of Human Rights Education (HRE are not radical.  The problem, we pointed out, with rights discourse is that it can mask the politics of how rights are defined, whose rights are recognized, and how they are enforced.  This problem becomes evident when HRE is bound up with a neoliberal, or worse than neoliberal, perspective that points fingers at others and rallies troops for supposedly humanitarian interventions while eliding the role of the United States as an imperializing settler colonial state.  Fortunately, we have once again received several essays that seem to us to be aware of this danger and provide admirable examples of radical teaching about human rights.

  14. Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries

    Science.gov (United States)

    Bottrill, Fiona E; Douglas, Stephen A; Hiley, C Robin; White, Richard

    2000-01-01

    The possible role of the endothelium in modulating responses to human urotensin-II (U-II) was investigated using isolated segments of rat thoracic aorta, small mesenteric artery, left anterior descending coronary artery and basilar artery.Human U-II was a potent vasoconstrictor of endothelium-intact isolated rat thoracic aorta (EC50=3.5±1.1 nM, Rmax=103±10% of control contraction induced by 60 mM KCl and 1 μM noradrenaline). However the contractile response was not significantly altered by removal of the endothelium or inhibition of nitric oxide synthesis with L-NAME (100 μM). Human U-II did not cause relaxation of noradrenaline-precontracted, endothelium-intact rat aortae.Human U-II contracted endothelium-intact rat isolated left anterior descending coronary arteries (EC50=1.3±0.8 nM, Rmax=20.1±4.9% of control contraction induced by 10 μM 5-HT). The contractile response was significantly enhanced by removal of the endothelium (Rmax=55.4±16.1%). Moreover, human U-II caused concentration-dependent relaxation of 5-HT-precontracted arteries, which was abolished by L-NAME or removal of the endothelium.No contractile effects of human U-II were found in rat small mesenteric arteries. However the peptide caused potent, concentration- and endothelium-dependent relaxations of methoxamine-precontracted vessels. The relaxant responses were potentiated by L-NAME (300 μM) but abolished in the additional presence of 25 mM KCl (which inhibits the actions of endothelium-derived hyperpolarizing factor).The present study is the first to show that human U-II is a potent endothelium-dependent vasodilator in some rat resistance vessels, and acts through release of EDHF as well as nitric oxide. Our findings have also highlighted clear anatomical differences in the responses of different vascular beds to human U-II which are likely to be important in determining the overall cardiovascular activity of this peptide. PMID:10952676

  15. The TFIID components human TAF(II)140 and Drosophila BIP2 (TAF(II)155) are novel metazoan homologues of yeast TAF(II)47 containing a histone fold and a PHD finger.

    Science.gov (United States)

    Gangloff, Y G; Pointud, J C; Thuault, S; Carré, L; Romier, C; Muratoglu, S; Brand, M; Tora, L; Couderc, J L; Davidson, I

    2001-08-01

    The RNA polymerase II transcription factor TFIID comprises the TATA binding protein (TBP) and a set of TBP-associated factors (TAF(II)s). TFIID has been extensively characterized for yeast, Drosophila, and humans, demonstrating a high degree of conservation of both the amino acid sequences of the constituent TAF(II)s and overall molecular organization. In recent years, it has been assumed that all the metazoan TAF(II)s have been identified, yet no metazoan homologues of yeast TAF(II)47 (yTAF(II)47) and yTAF(II)65 are known. Both of these yTAF(II)s contain a histone fold domain (HFD) which selectively heterodimerizes with that of yTAF(II)25. We have cloned a novel mouse protein, TAF(II)140, containing an HFD and a plant homeodomain (PHD) finger, which we demonstrated by immunoprecipitation to be a mammalian TFIID component. TAF(II)140 shows extensive sequence similarity to Drosophila BIP2 (dBIP2) (dTAF(II)155), which we also show to be a component of Drosophila TFIID. These proteins are metazoan homologues of yTAF(II)47 as their HFDs selectively heterodimerize with dTAF(II)24 and human TAF(II)30, metazoan homologues of yTAF(II)25. We further show that yTAF(II)65 shares two domains with the Drosophila Prodos protein, a recently described potential dTAF(II). These conserved domains are critical for yTAF(II)65 function in vivo. Our results therefore identify metazoan homologues of yTAF(II)47 and yTAF(II)65.

  16. Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes

    International Nuclear Information System (INIS)

    Chung, T.D.Y.; Drake, F.H.; Tan, K.B.; Per, S.R.; Crooke, S.T.; Mirabelli, C.K.

    1989-01-01

    Several DNA topoisomerase II partial cDNA clones obtained from a human Raji-HN2 cDNA library were sequenced and two classes of nucleotide sequences were found. One member of the first class, SP1, was identical to an internal fragment of human HeLa cell Topo II cDNA described earlier. A member of the second class, SP11, shared extensive nucleotide (75%) and predicted peptide (92%) sequence similarities with the first two-thirds of HeLa Topo II. Each class of cDNAs hybridized to unique, nonoverlapping restriction enzyme fragments of genomic DNA from several human cell lines. Synthetic 24-mer oligonucleotide probes specific for each cDNA class hybridized to 6.5-kilobase mRNAs; furthermore, hybridization of probe specific for one class was not blocked by probe specific for the other. Antibodies raised against a synthetic SP1-encoded dodecapeptide specifically recognized the 170-kDa form of Topo II, while antibodies raised against the corresponding SP11-encoded dodecapeptide, or a second unique SP11-encoded tridecapeptide, selectively recognized the 180-kDa form of Topo II. These data provide genetic and immunochemical evidence for two Topo II isozymes

  17. Quality of life philosophy II: what is a human being?

    Science.gov (United States)

    Ventegodt, Søren; Andersen, Niels Jørgen; Kromann, Maximilian; Merrick, Joav

    2003-12-01

    The human being is a complex matter and many believe that just trying to understand life and what it means to be human is a futile undertaking. We believe that we have to try to understand life and get a grip on the many faces of life, because it can be of great value to us to learn to recognize the fundamental principles of how life is lived to the fullest. Learning to recognize the good and evil forces of life helps us to make use of the good ones. To be human is to balance between hundreds of extremes. Sometimes we have to avoid these extremes, but at other times it seems we should pursue them, to better understand life. With our roots in medicine, we believe in the importance of love for better health. The secret of the heart is when reason and feelings meet and we become whole. Where reason is balanced perfectly by feelings and where mind and body come together in perfect unity, a whole new quality emerges, a quality that is neither feeling nor reason, but something deeper and more complete. In this paper, we outline only enough biology to clarify what the fundamental inner conflicts are about. The insight into these conflicts gives us the key to a great deal of the problems of life. To imagine pleasures greater than sensual pleasures seems impossible to most people. What could such a joy possibly be? But somewhere deep in life exists the finest sweetness, the greatest quality in life, the pure joy of being alive that emerges when we are fully present and life is in balance. This deep joy of life is what we call experiencing the meaning of life.

  18. Quality of Life Philosophy II: What is a Human Being?

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2003-01-01

    Full Text Available The human being is a complex matter and many believe that just trying to understand life and what it means to be human is a futile undertaking. We believe that we have to try to understand life and get a grip on the many faces of life, because it can be of great value to us to learn to recognize the fundamental principles of how life is lived to the fullest. Learning to recognize the good and evil forces of life helps us to make use of the good ones.To be human is to balance between hundreds of extremes. Sometimes we have to avoid these extremes, but at other times it seems we should pursue them, to better understand life. With our roots in medicine, we believe in the importance of love for better health. The secret of the heart is when reason and feelings meet and we become whole. Where reason is balanced perfectly by feelings and where mind and body come together in perfect unity, a whole new quality emerges, a quality that is neither feeling nor reason, but something deeper and more complete.In this paper, we outline only enough biology to clarify what the fundamental inner conflicts are about. The insight into these conflicts gives us the key to a great deal of the problems of life. To imagine pleasures greater than sensual pleasures seems impossible to most people. What could such a joy possibly be? But somewhere deep in life exists the finest sweetness, the greatest quality in life, the pure joy of being alive that emerges when we are fully present and life is in balance. This deep joy of life is what we call experiencing the meaning of life.

  19. Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases

    Science.gov (United States)

    2016-01-01

    Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. To identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. On the basis of previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10–100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons. (1) The activity of the metabolites was abrogated by a reducing agent. (2) Compounds inhibited topoisomerase II activity when they were incubated with the enzyme prior to the addition of DNA. (3) Compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID:26132160

  20. Backpack Weight and the Scaling of the Human Frame - II

    Science.gov (United States)

    O'Shea, Michael J.

    2018-02-01

    The backpack weight a hiker is capable of carrying depends on several factors. These include the hiker's weight, body mass index (BMI), fitness, and training. It can also depend on the terrain on which the hiker travels, e.g., off-trail or on-trail. However, online advice has tended to focus on the hiker's weight and suggests that pack weight should be a certain percentage of the hiker's weight. We developed a model of how the ability of a hiker to carry a backpack depends on the weight of the hiker. Modeling such real-life situations helps grab the attention of students in introductory physics. We have expanded on our earlier idea and present a more sophisticated model of an adult backpacker. In particular, we generalize our model for scaling of the human frame, and investigate how the ability to carry a backpack (within our model) varies with the form of scaling used.

  1. A role for human mitochondrial complex II in the production of reactive oxygen species in human skin

    Directory of Open Access Journals (Sweden)

    Alasdair Anderson

    2014-01-01

    Full Text Available The mitochondrial respiratory chain is a major generator of cellular oxidative stress, thought to be an underlying cause of the carcinogenic and ageing process in many tissues including skin. Previous studies of the relative contributions of the respiratory chain (RC complexes I, II and III towards production of reactive oxygen species (ROS have focussed on rat tissues and certainly not on human skin which is surprising as this tissue is regularly exposed to UVA in sunlight, a potent generator of cellular oxidative stress. In a novel approach we have used an array of established specific metabolic inhibitors and DHR123 fluorescence to study the relative roles of the mitochondrial RC complexes in cellular ROS production in 2 types of human skin cells. These include additional enhancement of ROS production by exposure to physiological levels of UVA. The effects within epidermal and dermal derived skin cells are compared to other tissue cell types as well as those harbouring a compromised mitochondrial status (Rho-zero A549. The results show that the complex II inhibitor, TTFA, was the only RC inhibitor to significantly increase UVA-induced ROS production in both skin cell types (P<0.05 suggesting that the role of human skin complex II in terms of influencing ROS production is more important than previously thought particularly in comparison to liver cells. Interestingly, two-fold greater maximal activity of complex II enzyme was observed in both skin cell types compared to liver (P<0.001. The activities of RC enzymes appear to decrease with increasing age and telomere length is correlated with ageing. Our study showed that the level of maximal complex II activity was higher in the MRC5/hTERT (human lung fibroblasts transfected with telomerase cells than the corresponding wild type cells (P=0.0012 which can be considered (in terms of telomerase activity as models of younger and older cells respectively.

  2. Pvu-II RFLP at the human lipoprotein lipase (LPL) gene locus

    Energy Technology Data Exchange (ETDEWEB)

    Li, S; Oka, K; Galton, D; Stocks, J

    1988-03-25

    Human lipoprotein lipase (LPL) cDNA, 1.6 Kbp, was isolated from human adipose cDNA library and subcloned into Bam HI site of pIB131. Pvu-II identifies a two allele polymorphism with bands at 7.0 Kb, 4.4 Kb and 2.5 Kb. The frequency was studied in 34 caucasians. The gene was assigned to 8p22. Co-dominant inheritance was demonstrated in a 2 generation family.

  3. Identification and characterization of the human type II collagen gene (COL2A1).

    NARCIS (Netherlands)

    K.S.E. Cheah (Kathryn); N.G. Stoker; J.R. Griffin; F.G. Grosveld (Frank); E. Solomon

    1985-01-01

    textabstractThe gene contained in the human cosmid clone CosHcol1, previously designated an alpha 1(I) collagen-like gene, has now been identified. CosHcol1 hybridizes strongly to a single 5.9-kilobase mRNA species present only in tissue in which type II collagen is expressed. DNA sequence analysis

  4. Human Rights and Peace Audit on Partition in South Asia - Phase II ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    3 févr. 2009 ... Human Rights and Peace Audit on Partition in South Asia - Phase II. In South Asia, people's social, political and cultural aspirations often get articulated as movements for territorially defined political change. Very often, these movements find resolution in partition or in an ethnic group/nationality getting ...

  5. Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

    DEFF Research Database (Denmark)

    Münstermann, U; Fritz, G; Seitz, G

    1990-01-01

    Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

  6. Isolation and characterization of recombinant human casein kinase II subunits alpha and beta from bacteria

    DEFF Research Database (Denmark)

    Grankowski, N; Boldyreff, B; Issinger, O G

    1991-01-01

    cDNA encoding the casein kinase II (CKII) subunits alpha and beta of human origin were expressed in Escherichia coli using expression vector pT7-7. Significant expression was obtained with E. coli BL21(DE3). The CKII subunits accounted for approximately 30% of the bacterial protein; however, most...

  7. Studies of the labelling of human serum albumin with 99mTc using Sn(II) tartrate and Sn(II)Cl2 as reducing agents

    International Nuclear Information System (INIS)

    El-Kolaly, M.T.; El-Asrag, H.A.; El-Wetery, A.S.; El-Mohty, A.A.

    1990-01-01

    A comparative study has been carried out on the effect of Sn(II) tartrate and Sn(II)Cl 2 on the labelling efficiency and tissue distribution of 99m Tc-human serum albumin. The effect of reductant content, reaction time (incubation time), albumin content, pH, and ascorbic acid on the efficiency of labelling and the tissue distribution of the labelled albumin has been investigated. The percentage of labelling was determined by paper and thin layer radiochromatography. Ascorbic acid shows no effect on either labelling efficiency or tissue distribution of 99m Tc-HSA prepared by Sn(II) tartrate or Sn(II)Cl 2 . (author)

  8. Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Budayova-Spano, Monika [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble (France); Fisher, S. Zoë [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Dauvergne, Marie-Thérèse [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Agbandje-McKenna, Mavis [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); Silverman, David N. [Department of Pharmacology and Therapeutics, PO Box 100267, University of Florida, Gainesville, FL 32610 (United States); Myles, Dean A. A. [European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France); Oak Ridge National Laboratory, PO Box 2008, Oak Ridge, TN 37831 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [Department of Biochemistry and Molecular Biology, PO Box 100245, University of Florida, Gainesville, FL 32610 (United States); European Molecular Biology Laboratory Grenoble Outstation, 6 Rue Jules Horowitz, 38042 Grenoble (France)

    2006-01-01

    This article reports the production, crystallization and X-ray structure determination of perdeuterated human carbonic anhydrase (HCA II). The refined structure is shown to be highly isomorphous with hydrogenated HCA II, especially with regard to the active site architecture and solvent network. Human carbonic anhydrase II (HCA II) is a zinc metalloenzyme that catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate, respectively. The rate-limiting step in catalysis is the intramolecular transfer of a proton between the zinc-bound solvent (H{sub 2}O/OH{sup −}) and the proton-shuttling residue His64. This distance (∼7.5 Å) is spanned by a well defined active-site solvent network stabilized by amino-acid side chains (Tyr7, Asn62, Asn67, Thr199 and Thr200). Despite the availability of high-resolution (∼1.0 Å) X-ray crystal structures of HCA II, there is currently no definitive information available on the positions and orientations of the H atoms of the solvent network or active-site amino acids and their ionization states. In preparation for neutron diffraction studies to elucidate this hydrogen-bonding network, perdeuterated HCA II has been expressed, purified, crystallized and its X-ray structure determined to 1.5 Å resolution. The refined structure is highly isomorphous with hydrogenated HCA II, especially with regard to the active-site architecture and solvent network. This work demonstrates the suitability of these crystals for neutron macromolecular crystallography.

  9. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  10. Human action contribution to ET-RR-II reactor systems unstems unavailability

    International Nuclear Information System (INIS)

    Sabek, M.G.

    2001-01-01

    This paper gives a study on the human action contribution to the systems unavailability of ET-RR-II reactor as a result of the test and maintenance procedures. The human contribution is expressed in terms of Fussel-Vesely importance which is defined by the probability that event is contributing to system failure (unavailability). The human error basic events contribution was analyzed for all initiating events and systems fault trees. The calculations result shows a high contribution value (61%) for the human error to systems unavailability. This means that the operator and the maintenance people should be highly qualified trained. Moreover, there should be programs for continuous training. Also, the procedures of tests and maintenance should be in a simple way and clear in order to minimize the contribution of the human errors. The calculations were done using the IRRAS cods

  11. Application of a fluorescent cobalamin analogue for analysis of the binding kinetics. A study employing recombinant human transcobalamin and intrinsic factor

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Grissom, Charles B; Fedosova, Natalya U

    2006-01-01

    facilitated detailed kinetic analysis of Cbl binding. We found that TC had the same affinity for CBC and Cbl (K(d) = 5 x 10(-15) m), whereas interaction of CBC with the highly specific protein IF was more complex. For instance, CBC behaved normally in the partial reactions CBC + IF(30) and CBC + IF(20) when...... complexes. We suggest that the correct domain-domain interactions are the most important factor during recognition and fixation of the ligands by IF. Dissociation of IF-CBC was biphasic, and existence of multiple protein-analogue complexes with normal and partially corrupted structure may explain...... this behaviour. The most stable component had K(d) = 1.5 x 10(-13) m, which guarantees the binding of CBC to IF under physiological conditions. The specific intestinal receptor cubilin bound both IF-CBC and IF-Cbl with equal affinity. In conclusion, the fluorescent analogue CBC can be used as a reporting agent...

  12. Detection of human papillomavirus in pterygium and conjunctival papilloma by hybrid capture II and PCR assays.

    Science.gov (United States)

    Takamura, Y; Kubo, E; Tsuzuki, S; Akagi, Y

    2008-11-01

    To elucidate the putative role of human papillomavirus (HPV) infection in pterygium and conjunctival papilloma. Hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays were performed to detect HPV in pterygium (42 samples obtained from 40 patients) and conjunctival papilloma (8 samples from 6 patients). The amount of HPV DNA was evaluated by measurement of relative light units (RLUs) on a luminometer. All papilloma samples were positive for HPV DNA by PCR and HC-II. The RLU values for specimens of recurrent and re-recurrent papilloma were markedly higher than those for specimens of primary lesions. HPV was detected by PCR in 2 of 42 (4.8%) beta-globin-positive pterygium specimens, whereas HC-II showed that HPV was negative in all pterygium samples. Our results support the hypothesis that HPV DNA is associated with the pathogenesis of conjunctival papilloma, but not pterygium. RLU measurement by HC-II may serve as a marker for evaluating the activity of HPV in conjunctival tumours.

  13. The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-γ

    International Nuclear Information System (INIS)

    Zhang Benyue; Li Ping; Wang Exing; Brahmi, Zacharie; Dunn, Kenneth W.; Blum, Janice S.; Roman, Ann

    2003-01-01

    Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-γ. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function

  14. Distribution of class ii major histocompatibility complex antigenexpressing cells in human dental pulp with carious lesions

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2012-09-01

    Full Text Available Background: Dental caries is a bacterial infection which causes destruction of the hard tissues of the tooth. Exposure of the dentin to the oral environment as a result of caries inevitably results in a cellular response in the pulp. The major histocompatibility complex (MHC is a group of genes that code for cell-surface histocompatibility antigens. Cells expressing class II MHC molecules participate in the initial recognition and the processing of antigenic substances to serve as antigen-presenting cells. Purpose: The aim of the study was to elucidate the alteration in the distribution of class II MHC antigen-expressing cells in human dental pulp as carious lesions progressed toward the pulp. Methods: Fifteen third molars with caries at the occlusal site at various stages of decay and 5 intact third molars were extracted and used in this study. Before decalcifying with 10% EDTA solution (pH 7.4, all the samples were observed by micro-computed tomography to confirm the lesion condition three-dimensionally. The specimens were then processed for cryosection and immunohistochemistry using an anti-MHC class II monoclonal antibody. Results: Class II MHC antigen-expressing cells were found both in normal and carious specimens. In normal tooth, the class II MHC-immunopositive cells were observed mainly at the periphery of the pulp tissue. In teeth with caries, class II MHC-immunopositive cells were located predominantly subjacent to the carious lesions. As the caries progressed, the number of class II MHC antigen-expressing cells was increased. Conclusion: The depth of carious lesions affects the distribution of class II MHC antigen-expressing cells in the dental pulp.Latar belakang: Karies merupakan penyakit infeksi bakteri yang mengakibatkan destruksi jaringan keras gigi. Dentin yang terbuka akibat karies akan menginduksi respon imun seluler pada pulpa. Kompleks histokompatibilitas utama (MHC merupakan sekumpulan gen yang mengkode histokompatibilitas

  15. An Integrated Human System Interaction (HSI) Framework for Human-Agent Team Collaboration, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — As space missions become more complex and as mission demands increase, robots, human-robot mixed initiative teams and software autonomy applications are needed to...

  16. MHC Class II and CD9 in Human Eosinophils Localize to Detergent-Resistant Membrane Microdomains

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C. N.; Spencer, Lisa A.

    2012-01-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor–stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR–containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4+ T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils. PMID:21885678

  17. MHC Class II and CD9 in human eosinophils localize to detergent-resistant membrane microdomains.

    Science.gov (United States)

    Akuthota, Praveen; Melo, Rossana C N; Spencer, Lisa A; Weller, Peter F

    2012-02-01

    Eosinophils function in murine allergic airways inflammation as professional antigen-presenting cells (APCs). In murine professional APC cell types, optimal functioning of MHC Class II depends on its lateral association in plasma membranes and colocalization with the tetraspanin CD9 into detergent-resistant membrane microdomains (DRMs). With human eosinophils, we evaluated the localization of MHC Class II (HLA-DR) to DRMs and the functional significance of such localization. In granulocyte-macrophage colony-stimulating factor-stimulated human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross-linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent methyl-β-cyclodextrin decreased eosinophil surface expression of HLA-DR and CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the first electron microscopy data of the ultrastructural immunolocalization of CD9 in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation (CD69 expression), proliferation, and cytokine production. Our results, which demonstrate that eosinophil MHC Class II localizes to DRMs in association with CD9 in a functionally significant manner, represent a novel insight into the organization of the antigen presentation complex of human eosinophils.

  18. Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type

    Energy Technology Data Exchange (ETDEWEB)

    Tomkinson, B.; Wernstedt, C.; Hellman, U.; Zetterqvist, Oe.

    1987-11-01

    The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with (/sup 3/H)diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residues 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases.

  19. Chymase-dependent generation of angiotensin II from angiotensin-(1-12 in human atrial tissue.

    Directory of Open Access Journals (Sweden)

    Sarfaraz Ahmad

    Full Text Available Since angiotensin-(1-12 [Ang-(1-12] is a non-renin dependent alternate precursor for the generation of cardiac Ang peptides in rat tissue, we investigated the metabolism of Ang-(1-12 by plasma membranes (PM isolated from human atrial appendage tissue from nine patients undergoing cardiac surgery for primary control of atrial fibrillation (MAZE surgical procedure. PM was incubated with highly purified ¹²⁵I-Ang-(1-12 at 37°C for 1 h with or without renin-angiotensin system (RAS inhibitors [lisinopril for angiotensin converting enzyme (ACE, SCH39370 for neprilysin (NEP, MLN-4760 for ACE2 and chymostatin for chymase; 50 µM each]. ¹²⁵I-Ang peptide fractions were identified by HPLC coupled to an inline γ-detector. In the absence of all RAS inhibitor, ¹²⁵I-Ang-(1-12 was converted into Ang I (2±2%, Ang II (69±21%, Ang-(1-7 (5±2%, and Ang-(1-4 (2±1%. In the absence of all RAS inhibitor, only 22±10% of ¹²⁵I-Ang-(1-12 was unmetabolized, whereas, in the presence of the all RAS inhibitors, 98±7% of ¹²⁵I-Ang-(1-12 remained intact. The relative contribution of selective inhibition of ACE and chymase enzyme showed that ¹²⁵I-Ang-(1-12 was primarily converted into Ang II (65±18% by chymase while its hydrolysis into Ang II by ACE was significantly lower or undetectable. The activity of individual enzyme was calculated based on the amount of Ang II formation. These results showed very high chymase-mediated Ang II formation (28±3.1 fmol × min⁻¹ × mg⁻¹, n = 9 from ¹²⁵I-Ang-(1-12 and very low or undetectable Ang II formation by ACE (1.1±0.2 fmol×min⁻¹ × mg⁻¹. Paralleling these findings, these tissues showed significant content of chymase protein that by immunocytochemistry were primarily localized in atrial cardiac myocytes. In conclusion, we demonstrate for the first time in human cardiac tissue a dominant role of cardiac chymase in the formation of Ang II from Ang-(1-12.

  20. c-Jun binds the N terminus of human TAF(II)250 to derepress RNA polymerase II transcription in vitro.

    Science.gov (United States)

    Lively, T N; Ferguson, H A; Galasinski, S K; Seto, A G; Goodrich, J A

    2001-07-06

    c-Jun is an oncoprotein that activates transcription of many genes involved in cell growth and proliferation. We studied the mechanism of transcriptional activation by human c-Jun in a human RNA polymerase II transcription system composed of highly purified recombinant and native transcription factors. Transcriptional activation by c-Jun depends on the TATA-binding protein (TBP)-associated factor (TAF) subunits of transcription factor IID (TFIID). Protein-protein interaction assays revealed that c-Jun binds with high specificity to the largest subunit of human TFIID, TAF(II)250. The region of TAF(II)250 bound by c-Jun lies in the N-terminal 163 amino acids. This same region of TAF(II)250 binds to TBP and represses its interaction with TATA boxes, thereby decreasing DNA binding by TFIID. We hypothesized that c-Jun is capable of derepressing the effect of the TAF(II)250 N terminus on TFIID-driven transcription. In support of this hypothesis, we found that c-Jun increased levels of TFIID-driven transcription in vitro when added at high concentrations to a DNA template lacking activator protein 1 (AP-1) sites. Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250. In addition to revealing a mechanism by which c-Jun activates transcription, our studies provide the first evidence that an activator can bind directly to the N terminus of TAF(II)250 to derepress RNA polymerase II transcription in vitro.

  1. The impact of the human DNA topoisomerase II C-terminal domain on activity.

    Directory of Open Access Journals (Sweden)

    Emma L Meczes

    2008-03-01

    Full Text Available Type II DNA topoisomerases (topos are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs.

  2. Functional substitution for TAF(II)250 by a retroposed homolog that is expressed in human spermatogenesis.

    Science.gov (United States)

    Wang, P Jeremy; Page, David C

    2002-09-15

    TAF(II)250, the largest subunit of the general transcription factor TFIID, is expressed from the human X chromosome, at least in somatic cells. In male meiosis, however, the sex chromosomes are transcriptionally silenced, while the autosomes remain active. How then are protein-encoding genes transcribed during human male meiosis? Here we present a novel autosomal human gene, TAF1L, which is homologous to TAF(II)250 and is expressed specifically in the testis, apparently in germ cells. We hypothesize that during male meiosis, transcription of protein-encoding genes relies upon TAF1L as a functional substitute for TAF(II)250. Like TAF(II)250, the human TAF1L protein can bind directly to TATA-binding protein, an essential component of TFIID. Most importantly, transfection with human TAF1L rescued the temperature-sensitive lethality of a hamster cell line mutant in TAF(II)250. TAF1L lacks introns and evidently arose by retroposition of a processed TAF(II)250 mRNA during primate evolution. The observation that TAF1L can functionally replace TAF(II)250 provides experimental support for the hypothesis that during male meiosis, autosomes provide cellular functions usually supplied by the X chromosome in somatic cells.

  3. Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.

    Science.gov (United States)

    Greenall, Sameer A; Bentley, John D; Pearce, Lesley A; Scoble, Judith A; Sparrow, Lindsay G; Bartone, Nicola A; Xiao, Xiaowen; Baxter, Robert C; Cosgrove, Leah J; Adams, Timothy E

    2013-01-04

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed "pro" and "big" IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling.

  4. Biochemical Characterization of Individual Human Glycosylated pro-Insulin-like Growth Factor (IGF)-II and big-IGF-II Isoforms Associated with Cancer

    Science.gov (United States)

    Greenall, Sameer A.; Bentley, John D.; Pearce, Lesley A.; Scoble, Judith A.; Sparrow, Lindsay G.; Bartone, Nicola A.; Xiao, Xiaowen; Baxter, Robert C.; Cosgrove, Leah J.; Adams, Timothy E.

    2013-01-01

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed “pro” and “big” IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling. PMID:23166326

  5. Regulated gene expression in cultured type II cells of adult human lung.

    Science.gov (United States)

    Ballard, Philip L; Lee, Jae W; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R; Fischer, Horst; Illek, Beate; Gonzales, Linda W; Kolla, Venkatadri; Matthay, Michael A

    2010-07-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.

  6. Chemical Rescue of Enzymes: Proton Transfer in Mutants of Human Carbonic Anhydrase II

    Science.gov (United States)

    Maupin, C. Mark; Castillo, Norberto; Taraphder, Srabani; Tu, Chingkuang; McKenna, Robert; Silverman, David N.; Voth, Gregory A.

    2011-01-01

    In human carbonic anhydrase II (HCA II) the mutation of position 64 from histidine to alanine (H64A) disrupts the rate limiting proton transfer (PT) event, resulting in a reduction of the catalytic activity of the enzyme as compared to the wild-type. Potential of mean force (PMF) calculations utilizing the multistate empirical valence bond (MS-EVB) methodology for H64A HCA II give a PT free energy barrier significantly higher than that found in the wild-type enzyme. This high barrier, determined in the absence of exogenous buffer and assuming no additional ionizable residues in the PT pathway, indicates the likelihood of alternate enzyme pathways that utilize either ionizable enzyme residues (self-rescue) and/or exogenous buffers (chemical rescue). It has been shown experimentally that the catalytic activity of H64A HCA II can be chemically rescued to near wild type levels by the addition of the exogenous buffer 4-methylimidazole (4MI). Crystallographic studies have identified two 4MI binding sites, yet site specific mutations intended to disrupt 4MI binding have demonstrated these sites to be non-productive. In the present work MS-EVB simulations show that binding of 4MI near Thr199 in the H64A HCA II mutant, a binding site determined by NMR spectroscopy, results in a viable chemical rescue pathway. Additional viable rescue pathways are also identified where 4MI acts as a proton transport intermediary from the active site to ionizable residues on the rim of the active site, revealing a probable mode of action for the chemical rescue pathway PMID:21452838

  7. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

    OpenAIRE

    Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

    1988-01-01

    In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems...

  8. Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Guo Yingqiang

    2010-05-01

    Full Text Available Abstract Background Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF is a member of the vascular endothelial growth factor (VEGF family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs and smooth muscle cells (VSMCs. Results In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2 in these cells. The Ang II type I receptor (AT1R antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2 and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs. Conclusion Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.

  9. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.

    Science.gov (United States)

    McLaughlin, M; Albertini, D F; Wallace, W H B; Anderson, R A; Telfer, E E

    2018-03-01

    Can complete oocyte development be achieved from human ovarian tissue containing primordial/unilaminar follicles and grown in vitro in a multi-step culture to meiotic maturation demonstrated by the formation of polar bodies and a Metaphase II spindle? Development of human oocytes from primordial/unilaminar stages to resumption of meiosis (Metaphase II) and emission of a polar body was achieved within a serum free multi-step culture system. Complete development of oocytes in vitro has been achieved in mouse, where in vitro grown (IVG) oocytes from primordial follicles have resulted in the production of live offspring. Human oocytes have been grown in vitro from the secondary/multi-laminar stage to obtain fully grown oocytes capable of meiotic maturation. However, there are no reports of a culture system supporting complete growth from the earliest stages of human follicle development through to Metaphase II. Ovarian cortical biopsies were obtained with informed consent from women undergoing elective caesarean section (mean age: 30.7 ± 1.7; range: 25-39 years, n = 10). Laboratory setting. Ovarian biopsies were dissected into thin strips, and after removal of growing follicles were cultured in serum free medium for 8 days (Step 1). At the end of this period secondary/multi-laminar follicles were dissected from the strips and intact follicles 100-150 μm in diameter were selected for further culture. Isolated follicles were cultured individually in serum free medium in the presence of 100 ng/ml of human recombinant Activin A (Step 2). Individual follicles were monitored and after 8 days, cumulus oocyte complexes (COCs) were retrieved by gentle pressure on the cultured follicles. Complexes with complete cumulus and adherent mural granulosa cells were selected and cultured in the presence of Activin A and FSH on membranes for a further 4 days (Step 3). At the end of Step 3, complexes containing oocytes >100 μm diameter were selected for IVM in SAGE medium (Step 4) then

  10. The Multi-Attribute Task Battery II (MATB-II) Software for Human Performance and Workload Research: A User's Guide

    Science.gov (United States)

    Santiago-Espada, Yamira; Myer, Robert R.; Latorella, Kara A.; Comstock, James R., Jr.

    2011-01-01

    The Multi-Attribute Task Battery (MAT Battery). is a computer-based task designed to evaluate operator performance and workload, has been redeveloped to operate in Windows XP Service Pack 3, Windows Vista and Windows 7 operating systems.MATB-II includes essentially the same tasks as the original MAT Battery, plus new configuration options including a graphical user interface for controlling modes of operation. MATB-II can be executed either in training or testing mode, as defined by the MATB-II configuration file. The configuration file also allows set up of the default timeouts for the tasks, the flow rates of the pumps and tank levels of the Resource Management (RESMAN) task. MATB-II comes with a default event file that an experimenter can modify and adapt

  11. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  12. Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Maaike Kockx

    Full Text Available Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs or directly target the GTPase domain (Dyngo or Dynole series, dose- and time- dependently reduced the secretion of apoE. SiRNA oligo's targeting all isoforms of dynamin II confirmed the involvement of dynamin II in apoE secretion. Inhibition of secretion was not mediated via effects on mRNA or protein synthesis. 2D-gel electrophoresis showed that inhibition occurred after apoE was processed and glycosylated in the Golgi and live cell imaging showed that inhibited secretion was associated with reduced post-Golgi movement of apoE-GFP-containing vesicles. The effect was not restricted to macrophages, and was not mediated by the effects of the inhibitors on microtubules. Inhibition of dynamin also altered the constitutive secretion of other proteins, decreasing the secretion of fibronectin, matrix metalloproteinase 9, Chitinase-3-like protein 1 and lysozyme but unexpectedly increasing the secretion of the inflammatory mediator cyclophilin A. We conclude that pharmacological inhibitors of dynamin II modulate the constitutive secretion of macrophage apoE as a class effect, and that their capacity to modulate protein secretion may affect a range of biological processes.

  13. Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.

    Science.gov (United States)

    Zucker-Franklin, D; Pancake, B A; Marmor, M; Legler, P M

    1997-06-10

    In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities.

  14. Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence

    Science.gov (United States)

    Zucker-Franklin, Dorothea; Pancake, Bette A.; Marmor, Michael; Legler, Patricia M.

    1997-01-01

    In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities. PMID:9177230

  15. Development of a ECOREA-II code for human exposures from radionuclides through food chain

    International Nuclear Information System (INIS)

    Yoo, D. H.; Choi, Y. H.

    2001-01-01

    The release of radionuclides from nuclear facilities following an accident into air results in human exposures through two pathways. One is direct human exposures by inhalation or dermal absorption of these radionucles. Another is indirect human exposures through food chain which includes intakes of plant products such as rice, vegetables from contaiminated soil and animal products such as meet, milk and eggs feeded by contaminated grasses or plants on the terrestial surface. This study presents efforts of the development of a computer code for the assessment of the indirect human exposure through such food chains. The purpose of ECOREA-II code is to develop appropriate models suitable for a specific soil condition in Korea based on previous experimental efforts and to provide a more user-friendly environment such as GUI for the use of the code. Therefore, the current code, when more fully developed, is expected to increase the understanding of environmental safety assessment of nuclear facilities following an accident and provide a reasonable regulatory guideline with respecte to food safety issues

  16. Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata.

    Science.gov (United States)

    Allen, A M; Chai, S Y; Clevers, J; McKinley, M J; Paxinos, G; Mendelsohn, F A

    1988-03-08

    Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.

  17. Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi-Fen; Shyu, Huey-Wen [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chang, Yi-Chuang [Department of Nursing, Fooyin University, Kaohsiung, Taiwan (China); Tseng, Wei-Chang [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Huang, Yeou-Lih [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China); Chen, Chang-Yu, E-mail: mt037@mail.fy.edu.tw [Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan (China)

    2012-03-01

    Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

  18. Nickel (II)-induced cytotoxicity and apoptosis in human proximal tubule cells through a ROS- and mitochondria-mediated pathway

    International Nuclear Information System (INIS)

    Wang, Yi-Fen; Shyu, Huey-Wen; Chang, Yi-Chuang; Tseng, Wei-Chang; Huang, Yeou-Lih; Lin, Kuan-Hua; Chou, Miao-Chen; Liu, Heng-Ling; Chen, Chang-Yu

    2012-01-01

    Nickel compounds are known to be toxic and carcinogenic in kidney and lung. In this present study, we investigated the roles of reactive oxygen species (ROS) and mitochondria in nickel (II) acetate-induced cytotoxicity and apoptosis in the HK-2 human renal cell line. The results showed that the cytotoxic effects of nickel (II) involved significant cell death and DNA damage. Nickel (II) increased the generation of ROS and induced a noticeable reduction of mitochondrial membrane potential (MMP). Analysis of the sub-G1 phase showed a significant increase in apoptosis in HK-2 cells after nickel (II) treatment. Pretreatment with N-acetylcysteine (NAC) not only inhibited nickel (II)-induced cell death and DNA damage, but also significantly prevented nickel (II)-induced loss of MMP and apoptosis. Cell apoptosis triggered by nickel (II) was characterized by the reduced protein expression of Bcl-2 and Bcl-xL and the induced the protein expression of Bad, Bcl-Xs, Bax, cytochrome c and caspases 9, 3 and 6. The regulation of the expression of Bcl-2-family proteins, the release of cytochrome c and the activation of caspases 9, 3 and 6 were inhibited in the presence of NAC. These results suggest that nickel (II) induces cytotoxicity and apoptosis in HK-2 cells via ROS generation and that the mitochondria-mediated apoptotic signaling pathway may be involved in the positive regulation of nickel (II)-induced renal cytotoxicity.

  19. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II.

    Science.gov (United States)

    Zanger, U M; Hauri, H P; Loeper, J; Homberg, J C; Meyer, U A

    1988-11-01

    In a subgroup of children with chronic active hepatitis, circulating autoantibodies occur that bind to liver and kidney endoplasmic reticulum (anti-liver/kidney microsome antibody type I or anti-LKM1). Anti-LKM1 titers follow the severity of the disease and the presence of these antibodies serves as a diagnostic marker for this autoimmune hepatitis type II. We demonstrate that anti-LKM1 IgGs specifically inhibit the hydroxylation of bufuralol in human liver microsomes. Using two assay systems with different selectivity for the two cytochrome P-450 isozymes catalyzing bufuralol metabolism in human liver, we show that anti-LKM1 exclusively recognizes cytochrome P-450db1. Immunopurification of the LKM1 antigen from solubilized human liver microsomes resulted in an electrophoretically homogenous protein that had the same molecular mass (50 kDa) as purified P-450db1 and an identical N-terminal amino acid sequence. Recognition of both purified P-450db1 and the immunoisolated protein on western blots by several monoclonal antibodies confirmed the identity of the LKM1 antigen with cytochrome P-450db1. Cytochrome P-450db1 has been identified as the target of a common genetic polymorphism of drug oxidation. However, the relationship between the polymorphic cytochrome P-450db1 and the appearance of anti-LKM1 autoantibodies as well as their role in the pathogenesis of chronic active hepatitis remains speculative.

  20. Antigen presentation and MHC class II expression by human esophageal epithelial cells: role in eosinophilic esophagitis.

    Science.gov (United States)

    Mulder, Daniel J; Pooni, Aman; Mak, Nanette; Hurlbut, David J; Basta, Sameh; Justinich, Christopher J

    2011-02-01

    Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Real-time dynamics of RNA Polymerase II clustering in live human cells

    Science.gov (United States)

    Cisse, Ibrahim

    2014-03-01

    Transcription is the first step in the central dogma of molecular biology, when genetic information encoded on DNA is made into messenger RNA. How this fundamental process occurs within living cells (in vivo) is poorly understood,[1] despite extensive biochemical characterizations with isolated biomolecules (in vitro). For high-order organisms, like humans, transcription is reported to be spatially compartmentalized in nuclear foci consisting of clusters of RNA Polymerase II, the enzyme responsible for synthesizing all messenger RNAs. However, little is known of when these foci assemble or their relative stability. We developed an approach based on photo-activation localization microscopy (PALM) combined with a temporal correlation analysis, which we refer to as tcPALM. The tcPALM method enables the real-time characterization of biomolecular spatiotemporal organization, with single-molecule sensitivity, directly in living cells.[2] Using tcPALM, we observed that RNA Polymerase II clusters form transiently, with an average lifetime of 5.1 (+/- 0.4) seconds. Stimuli affecting transcription regulation yielded orders of magnitude changes in the dynamics of the polymerase clusters, implying that clustering is regulated and plays a role in the cells ability to effect rapid response to external signals. Our results suggest that the transient crowding of enzymes may aid in rate-limiting steps of genome regulation.

  2. Conformational effects on the circular dichroism of Human Carbonic Anhydrase II: a multilevel computational study.

    Directory of Open Access Journals (Sweden)

    Tatyana G Karabencheva-Christova

    Full Text Available Circular Dichroism (CD spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII, with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions.

  3. Phaeophytins from Thyrsacanthus ramosissimus Moric. with inhibitory activity on human DNA topoisomerase II-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Cabral, Analucia Guedes Silveira; Tenorio-Souza, Fabio Henrique; Moura, Marcelo Dantas; Mota, Sabrina Gondim Ribeiro; Silva Lins, Antonio Claudio da; Dias, Celidarque da Silva; Barbosa-Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Frmaceuticas; Giulietti, Ana Maria [Universidade Estadual de Feira de Santana, Feira de Santana, BA (Brazil). Dept. de Ciencias Biologicas; Silva, Tania Maria Sarmento da [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Ciencias Moleculares; Santos, Creusioni Figueredo dos, E-mail: jbarbosa@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Biologia Molecular

    2012-07-01

    Our study reports the extraction and isolation of a new phaeophytin derivative 15{sup 1}-hydroxy-(15{sup 1}-S)-porphyrinolactone, designated anamariaine (1) herein, isolated from the chloroform fraction of aerial parts of Thyrsacanthus ramosissimus Moric. along with the known 15{sup 1}-ethoxy-(15{sup 1}-S)-porphyrinolactone (2). These compounds were identified by usual spectroscopic methods. Both compounds were subjected to in vitro (inhibitory activity) tests by means of supercoiled DNA relaxation techniques and were shown to display inhibitory activity against human DNA topoisomerase II-{alpha} at 50 {mu}M. Interconversion of these two pigments under the mild conditions of the isolation techniques should be highly unlikely but cannot be entirely ruled out. (author)

  4. Effects of human serun albumin in some biological properties of rhodium(II complexes

    Directory of Open Access Journals (Sweden)

    Espósito Breno P.

    2000-01-01

    Full Text Available The affinities for human albumin (HSA of five rhodium(II complexes of general formula [Rh2(bridge4] (bridge = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate were determined by spectrophotometry. In the case of the alkylcarboxylates, an inverse correlation of affinity with their liposolubilities was observed. Diffusion of the free or protein-bound complexes into Ehrlich cells in vitro seems to be primarily governed by the hydrophobic character of the complex. The complex [Rh2(tfc4] exhibited affinity towards the protein (K = 214.1 as well as cell partition both in the absence (32.1% and presence (48.6% of HSA. The compound HSA: [Rh2(tfc4] has had its antitumoral action in tumor-bearing Balb-c mice investigated, showing that HSA can be a drug reservoir for the rhodium complex.

  5. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); Tu, Chingkuang [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States)

    2014-06-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.

  6. Cytotoxicity of Diimine Palladium (II) Complexes of Alkyldithiocarbamate Derivatives on Human Lung, Ovary and Liver Cells.

    Science.gov (United States)

    Aryanpour, Narges; Mansouri-Torshizi, Hassan; Nakhjavan, Maryam; H Shirazi, Farshad

    2012-01-01

    Three new Complexes of formula [pd(bpy)(R-NH-CSS)] Cl (where bpy is 2/2'- bipyridine, and R-NH-CSS is butylamine, hexylamine- and octyamine-dithiocabamate anion) have been synthesized by University of Sistan and Blachostan. These complexes have been characterized by spectroscopic methods such as ultraviolet-visible, infrared and (1)H-NMR as well as conductivity measurements and chemical analysis. In these complexes, each of the dithiocarbamate ligands coordinates to Pd (II) center as bidentate with two sulfur atoms. We have found a 1:1 electrolyte in water conductivity test for the above mentioned compounds. To measure the biologic activity and potential anticancer efficacy of these compounds, they have been compared with cisplatin and its palladium analogue of [Pd (NH3)2 Cl2] on three different cell lines of human hepatocarcinoma HepG2, human ovarian carcinoma OV2008, and human lung adenocarcinoma A549. Clonogenic assay has shown LD50s in the range of 0.131±0.025 to 0.934 ± 0.194 for these compounds on above cell lines. In comparison, cisplatin has shown LD50s of 0.838 ± 0.074, 2.196 ± 0.220, and 2.799 ± 0.733 on OV2008, HepG2 and A549 cell lines, respectively. As a conclusion, above three new complexes have shown higher cytotoxicities compared to cisplatin on three different human cell lines. Based on biological tests, these compounds may potentially be considered as good anticancer candidates for further pharmacological studies.

  7. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    Directory of Open Access Journals (Sweden)

    Emilie Sundqvist

    2014-04-01

    Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and

  8. Hydroxyl Radical Formation from HULIS and Fe(II) Interactions: Fulvic Acid-Fe(II) Complexes in Simulated and Human Lung Fluids

    Science.gov (United States)

    Gonzalez, D.

    2017-12-01

    Inhalation of fine particulate matter (PM2.5) has long been associated with adverse health outcomes. However, the causative agents and underlying mechanisms for these health effects have yet to be identified. One hypothesis is that PM2.5 deposited in the alveoli produce an excess of highly reactive radicals, leading to oxidative stress. The OH radical may be the most physiologically damaging, capable of oxidizing of lipids, proteins and DNA. Due to the variability and uncertainty in PM2.5 composition, the components that contribute to OH formation are not well understood. Soluble Fe is a component of PM2.5that produces OH under physiological conditions. Humic-like substances are water soluble organics found in biomass burning and tobacco smoke. Humic-like substances are capable of binding to Fe and enhancing OH formation, but this chemistry is not well understood. In this work, we use soil derived fulvic acid as a surrogate for Humic-like substances and investigate its effect on OH formation from Fe(II) under conditions relevant to the lungs. We use a fluorescent OH trapping probe, chemical kinetics and thermodynamic modeling to investigate OH formation from fulvic acid and Fe(II) dissolved in simulated and human lung fluids. In simulated lung fluid, we find that fulvic acid binds to Fe(II) and enhances the rate of key reactions that form OH. When fulvic acid is added to human lung fluids containing Fe(II), an enhancement of OH formation is observed. In human lung fluid, fulvic acid and metal binding proteins compete for Fe binding. These metal binding proteins are typically not found in simulated lung fluids. Results show that fulvic acid strongly binds Fe(II) and catalyzes key reactions that form OH in both simulated and human lung fluids. These results may help explain the role of Humic-like substances and Fe in oxidative stress and adverse health outcomes. Furthermore, we suggest that future studies employ simulated lung fluids containing metal binding proteins

  9. Isolation and characterization of human cDNA clones encoding the α and the α' subunits of casein kinase II

    International Nuclear Information System (INIS)

    Lozeman, F.J.; Litchfield, D.W.; Piening, C.; Takio, Koji; Walsh, K.A.; Krebs, E.G.

    1990-01-01

    Casein kinase II is a widely distributed protein serine/threonine kinase. The holoenzyme appears to be a tetramer, containing two α or α' subunits (or one of each) and two β subunits. Complementary DNA clones encoding the subunits of casein kinase II were isolated from a human T-cell λgt 10 library using cDNA clones isolated from Drosophila melanogasten. One of the human cDNA clones (hT4.1) was 2.2 kb long, including a coding region of 1176 bp preceded by 156 bp (5' untranslated region) and followed by 871 bp (3' untranslated region). The hT4.1 close was nearly identical in size and sequence with a cDNA clone from HepG2 human hepatoma cultured cells. Another of the human T-cell cDNA clones (hT9.1) was 1.8 kb long, containing a coding region of 1053 bp preceded by 171 by (5' untranslated region) and followed by 550 bp (3' untranslated region). Amino acid sequences deduced from these two cDNA clones were about 85% identical. Most of the difference between the two encoded polypeptides was in the carboxy-terminal region, but heterogeneity was distributed throughout the molecules. Partial amino acid sequence was determined in a mixture of α and α' subunits from bovine lung casein kinase II. The bovine sequences aligned with the 2 human cDNA-encoded polypeptides with only 2 discrepancies out of 535 amino acid positions. This confirmed that the two human T-cell cDNA clones encoded the α and α' subunits of casein kinase II. These studies show that there are two distinct catalytic subunits for casein II (α and α') and that the sequence of these subunits is largely conserved between the bovine and the human

  10. BanII dimorphic site located in the third intron of the human apolipoprotein AI (APOA1) gene

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R T; Kresnak, M T; Frossard, P M

    1988-02-11

    A 0.7kb fragment generated by AvaII digestion of pBL13AI, a 0.965kb full-length human apolipoprotein AI cDNA was cloned into the EcoRI site of pBR322. The apoAI cDNA was isolated from a lambdagt10 human fetal liver cDNA library. BanII (GPuGCPyC) (International Biotechnologies, Inc.) identifies two invariant bands at 1122bp and 417bp, and a single two-allele polymorphism with bands at either 274bp or 452bp. The human apolipoprotein AI-CIII-AIV gene complex has been localized on the long arm of chromosome 11 by Southern blot analysis of human-chinese hamster cell hybrids. Co-dominant segregation has been observed in two families (13 individuals). The BanII restriction map was constructed from DNA sequence data of the human apoAI gene. The 452bp fragment is generated by the loss of a BanII dimorphic site in the third intron of the apoAI gene, between the 178bp and the 274bp fragments.

  11. Biophysical study on the interaction between two palladium(II) complexes and human serum albumin by Multispectroscopic methods

    Energy Technology Data Exchange (ETDEWEB)

    Saeidifar, Maryam, E-mail: saeidifar@merc.ac.ir [Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, Karaj (Iran, Islamic Republic of); Mansouri-Torshizi, Hassan [Department of Chemistry, University of Sistan and Baluchestan, Zahedan (Iran, Islamic Republic of); Akbar Saboury, Ali [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of)

    2015-11-15

    The interaction of [Pd(bpy)(n-pr-dtc)]Br (I) and ([Pd(phen)(n-pr-dtc)]Br (II) (bpy=2,2′-bipyridine, phen=1,10-phenanthroline and n-pr-dtc=n-propyldithiocarbamate) with human serum albumin (HSA) was investigated using fluorescence, UV–vis absorption and circular dichroism (CD) spectroscopy techniques under simulative physiological conditions (pH=7.4). It was observed that the two complexes interact with HSA via static fluorescence quenching. The thermodynamic parameters indicate that the binding process was spontaneous and that hydrogen bonds and van der Waals forces play a major role in the association of the HSA–Pd(II) complexes. The activation energy (E{sub a}), binding constant (K{sub b}) and number of binding sites (n) of the HSA–Pd(II) complexes were calculated from fluorescence data at 293 K, 303 K and 311 K. The conformational alternations of protein secondary structure in the presence of Pd(II) complexes were demonstrated using synchronous fluorescence, three-dimensional fluorescence spectra, UV–vis absorption and circular dichroism techniques. Furthermore, the apparent distance between donor (HSA) and acceptor (Pd(II) complexes) was determined using fluorescence resonance energy transfer (FRET). The binding studies between these complexes and HSA give us key insights into the transportation, distribution and toxicity of newly design antitumor Pd(II) complexes in human blood. - Highlights: • The HSA binding properties of two Palladium (II) complexes were studied. • Static quenching mechanism is effective in the interaction of HSA with Pd(II) complexes. • Hydrogen bonds and van der Waals forces were involved in the Pd(II) complexes–HSA interaction. • 3D fluorescence was used to study the interaction between two complexes and HSA.

  12. Reproduction in the space environment: Part II. Concerns for human reproduction

    Science.gov (United States)

    Jennings, R. T.; Santy, P. A.

    1990-01-01

    Long-duration space flight and eventual colonization of our solar system will require successful control of reproductive function and a thorough understanding of factors unique to space flight and their impact on gynecologic and obstetric parameters. Part II of this paper examines the specific environmental factors associated with space flight and the implications for human reproduction. Space environmental hazards discussed include radiation, alteration in atmospheric pressure and breathing gas partial pressures, prolonged toxicological exposure, and microgravity. The effects of countermeasures necessary to reduce cardiovascular deconditioning, calcium loss, muscle wasting, and neurovestibular problems are also considered. In addition, the impact of microgravity on male fertility and gamete quality is explored. Due to current constraints, human pregnancy is now contraindicated for space flight. However, a program to explore effective countermeasures to current constraints and develop the required health care delivery capability for extended-duration space flight is suggested. A program of Earth- and space-based research to provide further answers to reproductive questions is suggested.

  13. Isolation of an insulin-like growth factor II cDNA with a unique 5' untranslated region from human placenta

    International Nuclear Information System (INIS)

    Shen, Shujane; Daimon, Makoto; Wang, Chunyeh; Ilan, J.; Jansen, M.

    1988-01-01

    Human insulin-like growth factor II (IGF-II) cDNA from a placental library was isolated and sequenced. The 5' untranslated region (5'-UTR) sequence of this cDNA differs completely from that of adult human liver and has considerable base sequence identity to the same region of an IGF-II cDNA of a rat liver cell line, BRL-3A. Human placental poly(A) + RNA was probed with either the 5'-UTR of the isolated human placental IGF-II cDNA or the 5'-UTR of the IGF-II cDNA obtained from adult human liver. No transcripts were detected by using the 5'-UTR of the adult liver IGF-II as the probe. In contrast, three transcripts of 6.0, 3.2, and 2.2 kilobases were detected by using the 5'-UTR of the placental IGF-II cDNA as the probe or the probe from the coding sequence. A fourth IGF-II transcript of 4.9 kilobases presumably containing a 5'-UTR consisting of a base sequence dissimilar to that of either IGF-II 5'-UTR was apparent. Therefore, IGF-II transcripts detected may be products of alternative splicing as their 5'-UTR sequence is contained within the human IGF-II gene or they may be a consequence of alternative promoter utilization in placenta

  14. 18F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    International Nuclear Information System (INIS)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing; Pan, Donghui; Xu, Yuping; Yang, Min; Lang, Lixin; Niu, Gang; Chen, Xiaoyuan

    2015-01-01

    We report the biodistribution and radiation dosimetry of an integrin α v β 3 specific PET tracer 18 F-AlF-NOTA-E[PEG 4 -c(RGDfk)] 2 (denoted as 18 F-Alfatide II). We also assessed the value of 18 F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of 18 F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with 18 F-FDG (5.55 MBq/kg) and 18 F-Alfatide II. Injection of 18 F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. 18 F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by 18 F-Alfatide II PET, while only ten lesions were visualized by 18 F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that 18 F-Alfatide II is feasible for human studies. 18 F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  15. Low prevalence of antibodies to human T-lymphotropic virus-I/II among blood donors in eastern Saudi Arabia.

    Science.gov (United States)

    Fawaz, Naglaa A; Tamim, Hala; Almawi, Wassim Y

    2005-04-01

    The seroprevalence of human T-lymphotropic virus (HTLV)-I/II was assessed in 13,443 consecutive blood donors in eastern Saudi Arabia between 1998 and 2001. Screening by enzyme-linked immunosorbent assay (ELISA) and confirmation by Western blot resulted in 8 (0.060%) positive cases, of which 5 (0.056%) belonged to Saudi and 3 (0.113%) to non-Saudi donors. The majority of the HTLV-positive donations (6/8) were for patients, and none had a history of known risk factor for HTLV-I/II transmission. Although the very low prevalence of HTLV-I/II among Saudi donors does not support routine screening, screening of donors from other nationalities may be initiated, especially those from HTLV-I/II endemic areas.

  16. Competitive binding of Chlorin p6 and Dansyl-L-Proline to Sudlow's site II of human serum albumin

    Science.gov (United States)

    Patel, Sunita; Sharma, Kaushal Kishor; Datta, Anindya

    2015-03-01

    The binding of chlorin p6, a model photosensitizer for photodynamic therapy (PDT), to the Sudlow's site II of Human Serum Albumin (HSA) has been monitored by different spectroscopic methods. Displacement of Dansyl-L-Proline (DP) from its conjugate with HSA is manifested in the spectral shift and decrease in its fluorescence intensity as well as the emergence of component with lifetime of 2-3 ns, which is characteristic of free DP. As DP is known to bind specifically to the Sudlow's site II of human serum albumin, its displacement by chlorin p6 indicates the residence of the photosensitizer in the same site, in addition to Sudlow's site I. The binding constants for Sudlow's site II, determined by the stopped-flow technique, are found to be two orders of magnitude smaller than that for Sudlow's site I.

  17. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    Major histocompatibility complex (MHC) class II molecules have been implicated in cell adhesion in two ways. In addition to the well-established role of class II antigens in low-affinity adhesion provided by interactions between class II and CD4, recent data indicated that class II may also induce...... adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human...... class II-positive monocytic (I937) and T leukemic (HUT78) tumor cell lines and Epstein-Barr virus (EBV) transformed B-lymphoid cell lines (EBV-LCL). Class II-negative cell lines (U-937 and the EBV-LCL mutant line 616) were not induced to aggregate. An HLA-G-transfected EBV-LCL, 221-AGN...

  18. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation

    OpenAIRE

    Balamurugan, Appakalai N.; Green, Michael L.; Breite, Andrew G.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G.; Williams, Stuart K.; Hering, Bernhard J.; Dwulet, Francis E.; McCarthy, Robert C.

    2015-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation.

  19. TOPOISOMERASE-I AND TOPOISOMERASE-II ACTIVITY IN HUMAN BREAST, CERVIX, LUNG AND COLON-CANCER

    NARCIS (Netherlands)

    MCLEOD, HL; DOUGLAS, F; OATES, M; SYMONDS, RP; PRAKASH, D; VANDERZEE, AGJ; KAYE, SB; BROWN, R; KEITH, WN

    1994-01-01

    The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about

  20. Human insulin-like growth factor II leader 2 mediates internal initiation of translation

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Christiansen, Jan; Hansen, T.O.

    2002-01-01

    Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IG...

  1. Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies

    NARCIS (Netherlands)

    Vrielink, H.; Reesink, H. W.; Zaaijer, H. L.; van der Poel, C. L.; Cuypers, H. T.; Lelie, P. N.

    1996-01-01

    BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were

  2. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods.

    Directory of Open Access Journals (Sweden)

    Songhua Zhang

    Full Text Available H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.

  3. High-throughput sequencing of human plasma RNA by using thermostable group II intron reverse transcriptases

    Science.gov (United States)

    Qin, Yidan; Yao, Jun; Wu, Douglas C.; Nottingham, Ryan M.; Mohr, Sabine; Hunicke-Smith, Scott; Lambowitz, Alan M.

    2016-01-01

    Next-generation RNA-sequencing (RNA-seq) has revolutionized transcriptome profiling, gene expression analysis, and RNA-based diagnostics. Here, we developed a new RNA-seq method that exploits thermostable group II intron reverse transcriptases (TGIRTs) and used it to profile human plasma RNAs. TGIRTs have higher thermostability, processivity, and fidelity than conventional reverse transcriptases, plus a novel template-switching activity that can efficiently attach RNA-seq adapters to target RNA sequences without RNA ligation. The new TGIRT-seq method enabled construction of RNA-seq libraries from RNA in RNA in 1-mL plasma samples from a healthy individual revealed RNA fragments mapping to a diverse population of protein-coding gene and long ncRNAs, which are enriched in intron and antisense sequences, as well as nearly all known classes of small ncRNAs, some of which have never before been seen in plasma. Surprisingly, many of the small ncRNA species were present as full-length transcripts, suggesting that they are protected from plasma RNases in ribonucleoprotein (RNP) complexes and/or exosomes. This TGIRT-seq method is readily adaptable for profiling of whole-cell, exosomal, and miRNAs, and for related procedures, such as HITS-CLIP and ribosome profiling. PMID:26554030

  4. Analysis of angiotensin II binding to human platelets: Differences in young and old subjects

    International Nuclear Information System (INIS)

    Siebers, M.J.; Goodfriend, T.L.; Ball, D.; Elliott, M.E.

    1990-01-01

    We examined the binding of radiolabeled angiotensin II (AII) to human platelets to characterize the apparent increase in AII receptors observed in older subjects. At 22 degrees C, the amount of radioactivity associated with platelets from older subjects increased continuously for more than 2 hours. The same amount of radioactivity was displaced by addition of unlabeled AII at 30 min and 60 min. In the presence of phenylarsine oxide, in the cold, or when labeled antagonist was the ligand, binding came to equilibrium by 30 min. High pressure liquid chromatography demonstrated that 125 I-AII was the major radioactive compound in the supernatant and platelets after incubation, but the platelets also contained radiolabeled AII fragments. Thus, some degradation accompanied interaction of AII and platelets. Phenylarsine oxide did not prevent degradation of bound AII, suggesting that degradation precedes internalization. On average, maximum binding was greater in older subjects whether platelets were incubated with 125 I-AII alone, with 125 I-AII and phenylarsine oxide to prevent internalization, or when the competitive inhibitor 125 I-sar1,ile8-AII was the radioligand. Variability of binding among subjects also increased with age. Thus, platelets bind, degrade, and internalize AII, and the three processes occur to a greater extent in platelets from some, but not all older subjects

  5. Class I and II histone deacetylase expression in human chronic periodontitis gingival tissue.

    Science.gov (United States)

    Cantley, M D; Dharmapatni, A A S S K; Algate, K; Crotti, T N; Bartold, P M; Haynes, D R

    2016-04-01

    Histone deacetylase inhibitors (HDACi) are being considered to treat chronic inflammatory diseases at low doses. Currently HDACi that are more specific are being developed to target particular HDACs; therefore, this study aimed to determine levels and distribution of class I and II HDAC in human gingival samples obtained from patients with chronic periodontitis. Gingival biopsies were obtained from patients with and without (mild inflammation, no bone loss) periodontitis. Total RNA was isolated for real-time quantitative polymerase chain reaction to determine expression of HDACs 1-10. Immunohistochemistry was used to determine protein distribution of HDACs 1, 5, 8 and 9. Factor VIII, CD3 and tartrate resistant acid phosphatase (TRAP) were detected in serial sections to identify blood vessels, lymphocytes, pre-osteoclasts and osteoclasts cells respectively. Tumour necrosis factor α (TNF-α) expression was also assessed. mRNA for HDAC 1, 5, 8 and 9 were significantly upregulated in chronic periodontitis gingival tissues compared to non-periodontitis samples (p chronic periodontitis samples (p chronic periodontitis gingival tissues. HDAC 1, 5, 8 and 9 expression was higher in gingival tissues from patients with chronic periodontitis compared to non-periodontitis samples. Results suggest that these HDACs could therefore be targeted with specific acting HDACi. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. A clinical evaluation of a bioresorbable membrane and porous hydroxyapatite in the treatment of human molar class II furcations

    Directory of Open Access Journals (Sweden)

    K Gita Malathi

    2013-01-01

    Full Text Available Background: The ultimate goal of periodontal therapy is predictable regeneration of a functional attachment apparatus destroyed as a result of periodontitis. Reconstructive procedures have been used with varying success during the past decades to accomplish this goal. Aim: To evaluate whether the use of porous hydroxyapatite alone or a bioresorbable membrane alone would enhance the clinical results in the treatment of class II furcation defects in human lower molars. Materials and Methods: Fifteen patients with chronic periodontitis, aged between 39 and 49 years, with a pair of similar bilateral class II furcation defects (classification of Hamp et al. in mandibular first molars were selected. A split-mouth design was incorporated and the selected 30 furcation defects were assigned to one of the two treatment groups, i.e., Group I treated with a bioresorbable membrane from bovine-derived collagen guided tissue regeneration membrane and Group II treated using porous hydroxyapatite bone graft material on the contralateral sides. Evaluation of clinical parameters, probing depths and attachment levels, and radiographs was done preoperatively and 6 months postoperatively. Results: Both the groups showed statistically significant mean reduction in probing depths and gain in clinical attachment levels and linear bone fill. Comparison between Group I and Group II showed insignificant difference. Conclusion: Within the limits of this study, both the treatment modalities are beneficial for the treatment of human mandibular class II furcation defects.

  7. Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

    Directory of Open Access Journals (Sweden)

    Veronika Y. Sysoeva

    2017-12-01

    Full Text Available Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS. Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs. We examined the distribution of angiotensin receptor expressing cells in human adipose tissue and found that type 1 and type 2 receptors are co-expressed in its stromal compartment, which is known to contain mesenchymal stem cells. To study the expression of receptors specifically in ADSCs we have isolated them from adipose tissue. Up to 99% of cultured ADSCs expressed angiotensin II (AngII receptor type 1 (AT1. Using the analysis of Ca2+ mobilization in single cells we found that only 5.2 ± 2.7% of ADSCs specifically respond to serial Ang II applications via AT1 receptor and expressed this receptor constantly. This AT1const ADSCs subpopulation exhibited increased adipose competency, which was triggered by endogenous AngII. Inhibitory and expression analyses showed that AT1const ADSCs highly co-express AngII type 2 receptor (AT2, which was responsible for increased adipose competency of this ADSC subpopulation.

  8. PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

    Science.gov (United States)

    Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

    2017-08-01

    Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form

  9. Prevalence of human T-lymphotropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia.

    Science.gov (United States)

    Ul-Hassan, Zahoor; Al-Bahrani, Ahmad T; Panhotra, Bodh R

    2004-10-01

    Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II) infections can be transfusion associated, leading to tropical paraparesis, myelopathy and other neurological disorders. The aim of this study is to circumvent the risk of transmission through blood transfusion and to describe the prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the cost effectiveness of screening blood donors. The study was conducted at the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al-Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426 blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent assay test, during the 7 years of study period. The positive samples were confirmed by western blot analysis. Overall, HTLV-I antibody positivity (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood donors). None of the donor were positive for HTLV-II antibody. During the last 5 consecutive years of the study period (1999-2003), none of the donor was positive for HTLV-I/II antibody. Al-Hasa region is non-endemic for HTLV-I/II virus infections. Screening of native Saudi blood donors for these viruses does not appear to be cost effective.

  10. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

    Science.gov (United States)

    Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

    2017-03-01

    Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

  11. Type II collagen C2C epitope in human synovial fluid and serum after knee injury

    DEFF Research Database (Denmark)

    Kumahashi, N; Swärd, P; Larsson, S

    2015-01-01

    PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

  12. A Plea for the traditional family: Situating marriage within John Paul II's realist, or personalist, perspective of human freedom1

    Science.gov (United States)

    Schumacher, Michele M.

    2014-01-01

    This article is an attempt to defend the rights of the traditional family: not simply against the redefinition of marriage, but more fundamentally against a re-conceptualization of human freedom and human rights. To this end, it contrasts what Saint John Paul II calls an individualistic understanding of freedom and a personalistic notion of the same in order to argue that human freedom is called by the Creator to be in service of, and not in opposition to, the good of the human family. From this perspective—that of the social doctrine of the Catholic Church—it argues for the harmony between natural marriage and the respect of fundamental human rights, and it presents the social dimension of marriage as fundamental with respect to the legal and social protection of the family. PMID:25473131

  13. Effect of endocrine therapy on growth of T61 human breast cancer xenografts is directly correlated to a specific down-regulation of insulin-like growth factor II (IGF-II)

    DEFF Research Database (Denmark)

    Brünner, N; Yee, D; Kern, F G

    1993-01-01

    xenograft. Growth of the T61 tumour is inhibited by treatment with E2 and TAM. Ribonuclease (RNAse) protection assays with human- and mouse-specific IGF-II antisense probes were used to study the regulation of IGF-II mRNA by E2 and TAM in the tumour. IGF-II protein expression was studied by radioimmunoassay......-IR3 resulted in inhibition of tumour growth during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)...

  14. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    Energy Technology Data Exchange (ETDEWEB)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H. (Wistar Inst., Philadelphia, PA (United States))

    1991-04-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

  15. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

    International Nuclear Information System (INIS)

    DeFreitas, E.; Hilliard, B.; Cheney, P.R.; Bell, D.S.; Kiggundu, E.; Sankey, D.; Wroblewska, Z.; Palladino, M.; Woodward, J.P.; Koprowski, H.

    1991-01-01

    Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. The authors evaluted 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymerase chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS

  16. Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

    Science.gov (United States)

    Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

    2006-09-15

    Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

  17. Reaction Coordinate, Free Energy, and Rate of Intramolecular Proton Transfer in Human Carbonic Anhydrase II.

    Science.gov (United States)

    Paul, Sanjib; Paul, Tanmoy Kumar; Taraphder, Srabani

    2018-03-22

    The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been designed for each of these stages on the basis of classical and/or quantum mechanical-molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F( r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 10 6 s -1 , in close agreement with known experimental results.

  18. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Directory of Open Access Journals (Sweden)

    Katherine J Kasper

    2014-05-01

    Full Text Available Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS, how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6 mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.

  19. Changes in distribution of hepatic blood flow induced by intra-arterial infusion of angiotensin II in human hepatic cancer

    International Nuclear Information System (INIS)

    Sasaki, Y.; Imaoka, S.; Hasegawa, Y.

    1985-01-01

    Changes in the distribution of the hepatic blood flow induced by intra-arterial infusion of angiotensin II (AT-II) were studied in human hepatic cancers using extremely short-lived radioisotope (RI) (krypton 81 m [/sup 81m/Kr]; half-life, 13 seconds). After the start of continuous infusion of AT-II, the radioactivity of the tumor showed about a two-fold increase, whereas that of the nontumor region decreased to about one half as much as the level before the infusion. Consequently, the mean ratio of the arterial blood flow in the tumor region to that in the nontumor region (T/N ratio) increased to 3.30 (P less than 0.001). The T/N ratio showed a peak before the peripheral blood pressure reached the maximum, and thereafter tended to decrease. Intra-arterial infusion of AT-II raised the T/N ratio more obviously than did intravenous infusion of the drug, with less rise in the peripheral blood pressure. It is believed that intra-arterial infusion chemotherapy with local use of AT-II enables better accessibility of chemotherapeutic drugs to tumors

  20. Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(II) in human T hybridoma cells

    International Nuclear Information System (INIS)

    Guan Fuqin; Zhang Dongmei; Wang Xinchang; Chen Junhui

    2007-01-01

    Although effects of nickel(II) on the immune system have long been recognized, little is known about the effects of nickel(II) on the induction of apoptosis and related signaling events in T cells. In the present study, we investigated the roles and signaling pathways of nickel(II) in the induction of apoptosis in a human T cell line jurkat. The results showed that the cytotoxic effects of Ni involved significant morphological changes and chromosomal condensation (Hoechst 33258 staining). Analyses of hypodiploid cells and FITC-Annexin V and PI double staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h after nickel(II) treatment. Flow cytometry analysis also revealed that the loss of mitochondrial membrane potential (MMP) occurred concomitantly with the onset of NiCl 2 -induced apoptosis. Induction of apoptotic cell death by nickel was mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the generation of nitric oxide (NO). These results suggest that nickel(II) chloride induces jurkat cells apoptosis via nitric oxide generation, mitochondrial depolarization and bcl-2 suppression

  1. {sup 18}F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Chunjing; Mi, Baoming; Wan, Weixing [Affiliated Hospital of Jiangnan University (Wuxi No. 4 People' s Hospital), Department of Nuclear Medicine, Wuxi (China); Pan, Donghui; Xu, Yuping; Yang, Min [Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Wuxi (China); Lang, Lixin; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health, Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States)

    2015-12-15

    We report the biodistribution and radiation dosimetry of an integrin α{sub v}β{sub 3} specific PET tracer {sup 18}F-AlF-NOTA-E[PEG{sub 4}-c(RGDfk)]{sub 2} (denoted as {sup 18}F-Alfatide II). We also assessed the value of {sup 18}F-Alfatide II in patients with brain metastases. A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of {sup 18}F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with {sup 18}F-FDG (5.55 MBq/kg) and {sup 18}F-Alfatide II. Injection of {sup 18}F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. {sup 18}F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by {sup 18}F-Alfatide II PET, while only ten lesions were visualized by {sup 18}F-FDG, and 13 by CT. F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that {sup 18}F-Alfatide II is feasible for human studies. {sup 18}F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis. (orig.)

  2. Relative cytotoxicity of complexes of platinum(II and palladium(II against pure cell culture Paramecium caudatum and human cell lines A431 and HaCaT

    Directory of Open Access Journals (Sweden)

    Aleksei Vladimirovich Eremin

    2018-04-01

    Full Text Available The results of cytotoxicity cisplatin-like complexes of platinum(II and palladium(II are presented. The cytotoxicity was researched by method of  biotesting with Paramecium caudatum and by MTT-assay with human cells: epidermoid carcimoma A431 and minimal transformed aneuploid keratinocytes HaCaT. Cytotoxicity of complexes toward protists is high, however, comparatively HaCaT are more sensitive than A431. Furthemore, cytotoxicity of palladium(II complexes is higher than the analogues with platinum(II.

  3. Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Kazanji Mirdad

    2003-01-01

    Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

  4. Advanced 3D Human Simulation Components with Thermal/Haptic Feedback and Tissue Deformation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — In integrating the following three significant components for its research/research and development (R/R&D) effort, the power of this candidate Phase II project...

  5. Human urotensin II in internal mammary and radial arteries of patients undergoing coronary surgery

    DEFF Research Database (Denmark)

    Chen, Zhi-Wu; Yang, Qin; Huang, Yu

    2009-01-01

    (max):20.4+/-4.8%, p7.1%). The relaxation was abolished by endothelium denudation...... and by indomethacin, oxadiazoloquinoxalinone or N(omega)-nitro-L-arginine, oxyhemoglobin, and Ca2+-activated K+ channel (K(Ca)) blockers. Urotensin receptor mRNA was detected in both arteries. CONCLUSIONS: hU-II is an important spasmogen in arterial grafts with receptors expressed in IMA and RA. hU-II elicits...

  6. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

  7. Rapid radioimmunoassay of human apolipoproteins C-II and C-III

    Energy Technology Data Exchange (ETDEWEB)

    Gustafson, S; Oestlund-Lindqvist, A M; Vessby, B [Uppsala Univ. (Sweden)

    1984-06-01

    Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

  8. Cellular responses induced by Cu(II quinolinonato complexes in human tumor and hepatic cells

    Directory of Open Access Journals (Sweden)

    Trávníček Zdeněk

    2012-12-01

    Full Text Available Abstract Background Inspired by the unprecedented historical success of cisplatin, one of the most important research directions in bioinorganic and medicinal chemistry is dedicated to the development of new anticancer compounds with the potential to surpass it in antitumor activity, while having lower unwanted side-effects. Therefore, a series of copper(II mixed-ligand complexes of the type [Cu(qui(L]Y · xH2O (1–6, where Hqui = 2-phenyl-3-hydroxy-4(1H-quinolinone, Y = NO3 (1, 3, 5 or BF4 (2, 4, 6, and L = 1,10-phenanthroline (phen (1, 2, 5-methyl-1,10-phenanthroline (mphen (3, 4 and bathophenanthroline (bphen (5, 6, was studied for their in vitro cytotoxicity against several human cancer cell lines (A549 lung carcinoma, HeLa cervix epitheloid carcinoma, G361 melanoma cells, A2780 ovarian carcinoma, A2780cis cisplatin-resistant ovarian carcinoma, LNCaP androgen-sensitive prostate adenocarcinoma and THP-1 monocytic leukemia. Results The tested complexes displayed a stronger cytotoxic effect against all the cancer cells as compared to cisplatin. The highest cytotoxicity was found for the complexes 4 (IC50 = 0.36 ± 0.05 μM and 0.56 ± 0.15 μM, 5 (IC50 = 0.66 ± 0.07 μM and 0.73 ± 0.08 μM and 6 (IC50 = 0.57 ± 0.11 μM and 0.70 ± 0.20 μM against A2780, and A2780cis respectively, as compared with the values of 12.0 ± 0.8 μM and 27.0 ± 4.6 μM determined for cisplatin. Moreover, the tested complexes were much less cytotoxic to primary human hepatocytes than to the cancer cells. The complexes 5 and 6 exhibited significantly high ability to modulate secretion of the pro-inflammatory cytokines TNF-α (2873 ± 238 pg/mL and 3284 ± 139 pg/mL for 5, and 6 respectively and IL-1β (1177 ± 128 pg/mL and 1087 ± 101 pg/mL for 5, and 6 respectively tested on the lipopolysaccharide (LPS-stimulated THP-1 cells as compared with the values of 1173

  9. The Cu(II) affinity of the N-terminus of human copper transporter CTR1: Comparison of human and mouse sequences.

    Science.gov (United States)

    Bossak, Karolina; Drew, Simon C; Stefaniak, Ewelina; Płonka, Dawid; Bonna, Arkadiusz; Bal, Wojciech

    2018-05-01

    Copper Transporter 1 (CTR1) is a homotrimeric membrane protein providing the main route of copper transport into eukaryotic cells from the extracellular milieu. Its N-terminal extracellular domain, rich in His and Met residues, is considered responsible for directing copper into the transmembrane channel. Most of vertebrate CTR1 proteins contain the His residue in position three from N-terminus, creating a well-known Amino Terminal Cu(II)- and Ni(II)-Binding (ATCUN) site. CTR1 from humans, primates and many other species contains the Met-Asp-His (MDH) sequence, while some rodents including mouse have the Met-Asn-His (MNH) N-terminal sequence. CTR1 is thought to collect Cu(II) ions from blood copper transport proteins, including albumin, but previous reports indicated that the affinity of N-terminal peptide/domain of CTR1 is significantly lower than that of albumin, casting serious doubt on this aspect of CTR1 function. Using potentiometry and spectroscopic techniques we demonstrated that MDH-amide, a tripeptide model of human CTR1 N-terminus, binds Cu(II) with K of 1.3 × 10 13  M -1 at pH 7.4, ~13 times stronger than Human Serum Albumin (HSA), and MNH-amide is even stronger, K of 3.2 × 10 14  M -1 at pH 7.4. These results indicate that the N-terminus of CTR1 may serve as intermediate binding site during Cu(II) transfer from blood copper carriers to the transporter. MDH-amide, but not MNH-amide also forms a low abundance complex with non-ATCUN coordination involving the Met amine, His imidazole and Asp carboxylate. This species might assist Cu(II) relay down the peptide chain or its reduction to Cu(I), both steps necessary for the CTR1 function. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Can intradermal administration of angiotensin II influence human heat loss responses during whole body heat stress?

    Science.gov (United States)

    Fujii, Naoto; Meade, Robert D; Paull, Gabrielle; McGinn, Ryan; Foudil-bey, Imane; Akbari, Pegah; Kenny, Glen P

    2015-05-01

    It is unclear if angiotensin II, which can increase the production of reactive oxygen species (oxidative stress), modulates heat loss responses of cutaneous blood flow and sweating. We tested the hypothesis that angiotensin II-induced increases in oxidative stress impair cutaneous perfusion and sweating during rest and exercise in the heat. Eleven young (24 ± 4 yr) healthy adults performed two 30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C). The first and second exercises were followed by a 20- and 40-min recovery. Four microdialysis fibers were placed in the forearm skin for continuous administration of either: 1) lactated Ringer (control), 2) 10 μM angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10 μM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser-Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule) were evaluated at each skin site. Compared with control, angiotensin II reduced both CVC and sweating at baseline resting and during each recovery in the heat (all P 0.05). When ascorbate was coinfused with angiotensin II, the effect of angiotensin II on sweating was abolished (all P > 0.05); however, its effect on CVC at baseline resting and during each recovery remained intact (all P stress, while it impairs sweating through increasing oxidative stress during exposure to an ambient heat stress before and following exercise. Copyright © 2015 the American Physiological Society.

  11. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

    Directory of Open Access Journals (Sweden)

    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  12. Spectroscopic and molecular docking studies on the interaction of human serum albumin with copper(II) complexes

    Science.gov (United States)

    Guhathakurta, Bhargab; Pradhan, Ankur Bikash; Das, Suman; Bandyopadhyay, Nirmalya; Lu, Liping; Zhu, Miaoli; Naskar, Jnan Prakash

    2017-02-01

    Two osazone based ligands, butane-2,3-dione bis(2‧-pyridylhydrazone) (BDBPH) and hexane-3,4-dione bis(2‧-pyridylhydrazone) (HDBPH), were synthesized out of the 2:1 M Schiff base condensation of 2-hydrazino pyridine respectively with 2,3-butanedione and 3,4-hexanedione. The X-ray crystal structures of both the ligands have been determined. The copper(II) complex of HDBPH has also been synthesized and structurally characterized. HDBPH and its copper(II) complex have thoroughly been characterized through various spectroscopic and analytical techniques. The X-ray crystal structure of the copper complex of HDBPH shows that it is a monomeric Cu(II) complex having 'N4O2' co-ordination chromophore. Interaction of human serum albumin (HSA) with these ligands and their monomeric copper(II) complexes have been studied by various spectroscopic means. The experimental findings show that the ligands as well as their copper complexes are good HSA binders. Molecular docking investigations have also been done to unravel the mode of binding of the species with HSA.

  13. The dormant and the fully competent oocyte: comparing the transcriptome of human oocytes from primordial follicles and in metaphase II

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Vikeså, Jonas

    2013-01-01

    Oocytes become enclosed in primordial follicles during fetal life and remain dormant there until activation followed by growth and meiotic resumption. Current knowledge about the molecular pathways involved in oogenesis is incomplete. This study identifies the specific transcriptome of the human...... oocyte in the quiescent state and at the pinnacle of maturity at ovulation. In silico bioinformatic comparisons were made between the transcriptome of human oocytes from dormant primordial follicles and that of human metaphase II (MII) oocytes and granulosa cells and unique gene expression profiles were...... identified as well as functional and pathway enrichments associated with the oocytes from the two developmental hallmarks. A total of 729 genes were highly enriched in oocytes from primodial follicles and 1456 genes were highly enriched in MII oocytes (>10-fold, P...

  14. Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

    Science.gov (United States)

    Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

    2014-01-01

    Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

  15. RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II

    Directory of Open Access Journals (Sweden)

    Isabel X. Wang

    2014-03-01

    Full Text Available RNA sequences are expected to be identical to their corresponding DNA sequences. Here, we found all 12 types of RNA-DNA sequence differences (RDDs in nascent RNA. Our results show that RDDs begin to occur in RNA chains ∼55 nt from the RNA polymerase II (Pol II active site. These RDDs occur so soon after transcription that they are incompatible with known deaminase-mediated RNA-editing mechanisms. Moreover, the 55 nt delay in appearance indicates that they do not arise during RNA synthesis by Pol II or as a direct consequence of modified base incorporation. Preliminary data suggest that RDD and R-loop formations may be coupled. These findings identify sequence substitution as an early step in cotranscriptional RNA processing.

  16. Characterization of casein kinase II in human colonic carcinomas after heterotransplantation into nude mice

    DEFF Research Database (Denmark)

    Seitz, G; Münstermann, U; Schneider, H R

    1989-01-01

    Casein kinase II (CKII) activity in colorectal tumours was compared before and after heterotransplantation onto nude mice. The test revealed that the enzyme activity was about two-fold enhanced in the tumours isolated from the nude mice when compared to the respective primary tumours from which...

  17. Effect of Collagen Type I or Type II on Chondrogenesis by Cultured Human Articular Chondrocytes

    NARCIS (Netherlands)

    Rutgers, M.; Saris, Daniël B.F.; Vonk, L.A.; van Rijen, M.H.P.; Akrum, V.; Langeveld, D.; van Boxtel, A.; Dhert, W.J.A.; Creemers, L.B.

    2013-01-01

    Introduction: Current cartilage repair procedures using autologous chondrocytes rely on a variety of carriers for implantation. Collagen types I and II are frequently used and valuable properties of both were shown earlier in vitro, although a preference for either was not demonstrated. Recently,

  18. Pulmonary function testing in HTLV-I and HTLV-II infected humans: a cohort study

    Directory of Open Access Journals (Sweden)

    Garratty George

    2003-07-01

    Full Text Available Abstract Background HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function. Methods We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study (HOST, including vital capacity (VC, forced expiratory volume in one second (FEV1, and diffusing lung capacity for carbon monoxide (DLCO corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history. Results Mean (standard deviation pulmonary function values among the 257 subjects were as follows: FVC = 3.74 (0.89 L, FEV1 = 2.93 (0.67 L, DLCOcorr = 23.82 (5.89 ml/min/mmHg, alveolar ventilation (VA = 5.25 (1.20 L and DLCOcorr/VA = 4.54 (0.87 ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCOcorr/VA by HTLV status. For DLCOcorr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding. Conclusions There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.

  19. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

    OpenAIRE

    Day, Cheryl L.; Seth, Nilufer P.; Lucas, Michaela; Appel, Heiner; Gauthier, Laurent; Lauer, Georg M.; Robbins, Gregory K.; Szczepiorkowski, Zbigniew M.; Casson, Deborah R.; Chung, Raymond T.; Bell, Shannon; Harcourt, Gillian; Walker, Bruce D.; Klenerman, Paul; Wucherpfennig, Kai W.

    2003-01-01

    Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells has not been achieved. To further define the phenotype and function of these cells, we developed a novel approach for the generation of tetrameric forms of MHC class II/peptide complexes that is based on the cellular peptide-exchange mechanism. HLA-DR molecules were expressed as precursors with a c...

  20. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome

    International Nuclear Information System (INIS)

    Lewis, S.E.; Barnett, L.B.; Erickson, R.P.; Venta, P.J.; Tashian, R.E.

    1988-01-01

    Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

  1. Drugs associated with teratogenic mechanisms. Part II : a literature review of the evidence on human risks

    NARCIS (Netherlands)

    van Gelder, Marleen M. H. J.; de Jong-van den Berg, Lolkje T. W.; Roeleveld, Nel

    What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with teratogenic mechanisms. Medical drugs

  2. Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks

    NARCIS (Netherlands)

    Gelder, M.M.H.J. van; Jong-van den Berg, L.T. de; Roeleveld, N.

    2014-01-01

    STUDY QUESTION: What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms? SUMMARY ANSWER: Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with

  3. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22

    International Nuclear Information System (INIS)

    Tsai-Pflugfelder, M.; Liu, L.F.; Liu, A.A.; Tewey, K.M.; Whang-Peng, J.; Knutsen, T.; Huebner, K.; Croce, C.M.; Wang, J.C.

    1988-01-01

    Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage λ was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a λgt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the gene was mapped to chromosome 17q21-22 by in situ hybridization of a cloned fragment to metaphase chromosomes and by hybridization analysis with a panel of mouse-human hybrid cell lines, each retaining a subset of human chromosomes

  4. The Influence of Class II Division 2 Malocclusions on the Harmony of the Human Face Profile.

    Science.gov (United States)

    Perović, Tatjana

    2017-11-24

    BACKGROUND Persons with class II division 2 malocclusion are characterized by a very specific dento-skeletal and soft-tissue profile (a profile in which a protruding nose and chin, retruding lips, concave and shortened lower third of the face, and gummy smile are dominant), which is the opposite of the currently modern profiles (convex profile of protruding lips and small chin). The aim of this research was to determine the differences in parameters of harmonies of facial profiles between persons with class II division 2 malocclusions and class I, and to establish the significance of those differences. MATERIAL AND METHODS For this study, 50 patients with class II division 2 malocclusions and 50 patients with class I were selected; profile photos were recorded and a photometric analysis was done: a type of profile according to Schwarz, the shape of a nose, the prominence of chin, biometrical field, the position of lips in relation to the tangent Sn-Pg, S-line (Steiner), E-line (Riketts) and a facial angle according to Arnett. RESULTS The significant differences in profiles of persons with class II division 2 compared to class I were: position and prominence of the chin, the position of the lower and upper lip in relation to the S-line, and smaller value of a facial angle in relation to persons with class I. CONCLUSIONS The differences seen in skeletal profiles were not associated with significant differences in the profiled facial contours of the examined groups. The compensatory role of the fullness of soft tissues of the lips is probably the reason why there were not significant deviations in all the examined parameters.

  5. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast...

  6. The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

    Science.gov (United States)

    Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

    2017-08-11

    The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

  7. Human Reliability analysis for digitized nuclear power plants: Case study on the LingAo II nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yan Hua; Zhang, Li [Institute of Human Factors Engineering AND Safety Management, Hunan Institute of Technology, Hengyang (China); Dai, Cao; Li, Peng Cheng; Qing, Tao [Human Factors Institute, University of South China, Hengyang (China)

    2017-03-15

    The main control room (MCR) in advanced nuclear power plants (NPPs) has changed from analog to digital control system (DCS). Operation and control have become more automated, centralized, and accurate due to the digitalization of NPPs, which has improved the efficiency and security of the system. New issues associated with human reliability inevitably arise due to the adoption of new accident procedures and digitalization of main control rooms in NPPs. The LingAo II NPP is the first digital NPP in China to apply the state-oriented procedure. In order to address issues related to human reliability analysis for DCS and DCS + state-oriented procedure, the Hunan Institute of Technology conducted a research project based on a cooperative agreement with the LingDong Nuclear Power Co. Ltd. This paper is a brief introduction to the project.

  8. Human Reliability Analysis for Digitized Nuclear Power Plants: Case Study on the LingAo II Nuclear Power Plant

    Directory of Open Access Journals (Sweden)

    Yanhua Zou

    2017-03-01

    Full Text Available The main control room (MCR in advanced nuclear power plants (NPPs has changed from analog to digital control system (DCS. Operation and control have become more automated, centralized, and accurate due to the digitalization of NPPs, which has improved the efficiency and security of the system. New issues associated with human reliability inevitably arise due to the adoption of new accident procedures and digitalization of main control rooms in NPPs. The LingAo II NPP is the first digital NPP in China to apply the state-oriented procedure. In order to address issues related to human reliability analysis for DCS and DCS + state-oriented procedure, the Hunan Institute of Technology conducted a research project based on a cooperative agreement with the LingDong Nuclear Power Co. Ltd. This paper is a brief introduction to the project.

  9. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II.

    Science.gov (United States)

    Doublier, Sophie; Salvidio, Gennaro; Lupia, Enrico; Ruotsalainen, Vesa; Verzola, Daniela; Deferrari, Giacomo; Camussi, Giovanni

    2003-04-01

    We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 +/- 9%; P < 0.001) and type 2 (65 +/- 10%; P < 0.001) diabetic patients with diabetes and nephrotic syndrome when compared with control subjects. The pattern of staining shifted from punctate/linear distribution to granular. In patients with microalbuminuria, the staining pattern of nephrin also showed granular distribution and reduction intensity of 69% in the patient with type 1 diabetes and of 62 +/- 4% (P < 0.001) in the patients with type 2 diabetes. In vitro studies on human cultured podocytes demonstrated that glycated albumin and angiotensin II reduced nephrin expression. Glycated albumin inhibited nephrin synthesis through the engagement of receptor for advanced glycation end products, whereas angiotensin II acted on cytoskeleton redistribution, inducing the shedding of nephrin. This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.

  10. Building human resources capability in health care: a global analysis of best practice--Part II.

    Science.gov (United States)

    Zairi, M

    1998-01-01

    This paper is the second from a series of three, addressing human resource practices using best practice examples. The analysis covered is based on the experiences of organisations that have won the Malcolm Baldrige National Quality Award (MBNQA) in the USA. The subcriteria covered in this benchmarking comparative analysis covers the following areas: human resource planning and management; employee involvement; employee education and training; employee performance and recognition; employee wellbeing and satisfaction. The paper concludes by reflecting on the likely implications for health-care professionals working in the human resource field.

  11. Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

    International Nuclear Information System (INIS)

    Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

    2006-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

  12. Human factors analysis and design methods for nuclear waste retrieval systems. Volume II. A compendium of human factors design data

    International Nuclear Information System (INIS)

    Casey, S.M.

    1980-04-01

    This document is a compilation of human factors engineering design recommendations and data, selected and organized to assist in the design of a nuclear waste retrieval system. Design guidelines from a variety of sources have been evaluated, edited, and expanded for inclusion in this document, and, where appropriate, portions of text from selected sources have been included in their entirety. A number of human factors engineering guidelines for equipment designers have been written over the past three decades, each tailored to the needs of the specific system being designed. In the case of this particular document, a review of the preliminary human operator functions involved in each phase of the retrieval process was performed, resulting in the identification of areas of design emphasis upon which this document should be based. Documents containing information and design data on each of these areas were acquired, and data and design guidelines related to the previously identified areas of emphasis were extracted and reorganized. For each system function, actions were first assigned to operator and/or machine, and the operator functions were then described. Separate lists of operator functions were developed for each of the areas of retrieval activities - survey and mapping, remining, floor flange emplacement, plug and canister overcoring, plug and canister removal and transport, and CWSRS activity. These functions and the associated man-machine interface were grouped into categories based on task similarity, and the principal topics of human factors design emphasis were extracted. These topic areas are reflected in the contents of the 12 sections of this document

  13. Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice

    Directory of Open Access Journals (Sweden)

    Mühlfeld Christian

    2007-10-01

    Full Text Available Abstract Background Surfactant protein D (SP-D deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. Methods SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. Main Results After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Conclusion Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are

  14. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  15. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  16. Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines

    Science.gov (United States)

    Hernández, Wilfredo; Paz, Juan; Carrasco, Fernando; Spodine, Evgenia; Manzur, Jorge; Sieler, Joachim; Blaurock, Steffen; Beyer, Lothar

    2013-01-01

    The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1 (1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2 (2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3 (3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4 (4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5 (5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and 1H- and 13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex 6 shows a square planar geometry with two deprotonated ligands coordinated to PdII through the azomethine nitrogen and thione sulfur atoms in a cis arrangement. The in vitro cytotoxic activity measurements indicate that the palladium(II) complexes (IC50 = 0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50 = 23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.). PMID:24391528

  17. Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(II).

    Science.gov (United States)

    Cheng, Robert Y S; Zhao, Ailian; Alvord, W Gregory; Powell, Douglas A; Bare, Robert M; Masuda, Akira; Takahashi, Takashi; Anderson, Lucy M; Kasprzak, Kazimierz S

    2003-08-15

    Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix.

  18. Biosynthesis of 10 kDa and 7.5 kDa insulin-like growth factor II in a human rhabdomyosarcoma cell line

    DEFF Research Database (Denmark)

    Nielsen, F C; Haselbacher, G; Christiansen, Jan

    1993-01-01

    In the present study we have analysed the expression of insulin-like growth factor II (IGF-II) in the human rhabdomyosarcoma cell line IN157.IN157 cells express high levels of three IGF-II mRNAs of 6.0 kb, 4.8 kb and 4.2 kb. In contrast, normal skeletal muscle expresses a negligible amount of IGF......-II mRNA. Two forms of IGF-II with molecular masses of 7.5 kDa and 10 kDa, corresponding to the mature IGF-II and IGF-II with a C-terminal extension of 21 amino acids (IGF-IIE21), were secreted into the culture medium at amounts of 17 ng/ml (2.3 nM) and 15 ng/ml (1.5 nM), respectively. IN157 cells also......-II and IGF-IIE21 with Kd values of 0.5 nM and 2 nM, respectively, and IGF-I with about 500 times lower affinity. IGF-II and IGF-IIE21 stimulated DNA synthesis via the IGF-I receptor, whereas the IGF-II/Man 6-P receptor mediated their rapid internalization and inactivation. During culture of IN157 cells about...

  19. Angiotensin II Regulates microRNA-132/-212 in Hypertensive Rats and Humans

    DEFF Research Database (Denmark)

    Eskildsen, Tilde V; Jeppesen, Pia L; Schneider, Mikael

    2013-01-01

    MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, are emerging as key regulators in cardiovascular development and disease. MiRNAs are involved in cardiac hypertrophy, heart failure and remodeling following cardiac infarction; however, mi...... no effect. Taken together, these data suggest that miR-132 and miR-212 are involved in AngII induced hypertension, providing a new perspective in hypertensive disease mechanisms....

  20. Regulatory T cells in human and angiotensin II-induced mouse abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Zhou, Yi; Wu, Wenxue; Lindholt, Jes S

    2015-01-01

    concentration in blood cell lysates from 485 AAA patients and 204 age- and sex-matched controls. AAA patients exhibited lower blood cell Foxp3 expression than controls (P Pearson's correlation test demonstrated a significant but negative correlation between Foxp3 and AAA annual expansion rate before...... (r = -0.147, P = 0.007) and after (r = -0.153, P = 0.006) adjustment for AAA risk factors. AAA in apolipoprotein E-deficient (Apoe(-/-)) mice that received different doses of Ang-II exhibited a negative correlation of lesion Foxp3(+) Treg numbers with AAA size (r = -0.883, P

  1. Recombinant pollen allergens from Dactylis glomerata: preliminary evidence that human IgE cross-reactivity between Dac g II and Lol p I/II is increased following grass pollen immunotherapy.

    Science.gov (United States)

    Roberts, A M; Van Ree, R; Cardy, S M; Bevan, L J; Walker, M R

    1992-07-01

    We previously described the isolation of three identical complementary DNA (cDNA) clones, constructed from Orchard/Cocksfoot grass (Dactylis glomerata) anther messenger RNA (mRNA), expressing a 140,000 MW beta-galactosidase fusion protein recognized by IgE antibodies in atopic sera. Partial nucleotide sequencing and inferred amino acid sequence showed greater than 90% homology with the group II allergen from Lolium perenne (Lol II) indicating they encode the group II equivalent, Dac g II. Western blot immunoprobing of recombinant lysates with rabbit polyclonal, mouse monoclonal and human polyclonal antisera demonstrates immunological identity between recombinant Dac g II, Lol p I and Lol p II. Similar cross-identity is observed with pollen extracts from three other grass species: Festuca rubra, Phleum pratense and Anthoxanthum odoratum. Recombinant Dac g II was recognized by species- and group-cross-reactive human IgE antibodies in 33% (4/12) of sera randomly selected from grass-sensitive individuals and in 67% (14/21) of sera from patients receiving grass pollen immunotherapy, whilst 0/4 sera from patients receiving venom immunotherapy alone contained Dac g II cross-reactive IgE. Cross-reactive IgG4 antibodies were detectable in 95% of sera from grass pollen immunotherapy patients. These preliminary data suggest that conventional grass pollen allergoid desensitization immunotherapy may induce IgE responses to a cross-reactive epitope(s) co-expressed by grass pollen groups I and II (and possibly group III) allergens.

  2. Human brain as the model of a new computer system. II

    Energy Technology Data Exchange (ETDEWEB)

    Holtz, K; Langheld, E

    1981-12-09

    For Pt. I see IBID., Vol. 29, No. 22, P. 13 (1981). The authors describe the self-generating system of connections of a self-teaching no-program associative computer. The self-generating systems of connections are regarded as simulation models of the human brain and compared with the brain structure. The system hardware comprises microprocessor, PROM, memory, VDU, keyboard unit.

  3. Proteomic analysis of human metaphase chromosomes reveals Topoisomerase II alpha as an Aurora B substrate

    DEFF Research Database (Denmark)

    Morrison, Ciaran; Henzing, Alexander J; Jensen, Ole Nørregaard

    2002-01-01

    B in the presence of radioactive ATP. Immunoblot analysis confirmed the HeLa scaffold fraction to be enriched for known chromosomal proteins including CENP-A, CENP-B, CENP-C, ScII and INCENP. Mass spectrometry of bands excised from one-dimensional polyacrylamide gels further defined the protein......The essential Aurora B kinase is a chromosomal passenger protein that is required for mitotic chromosome alignment and segregation. Aurora B function is dependent on the chromosome passenger, INCENP. INCENP, in turn, requires sister chromatid cohesion for its appropriate behaviour. Relatively few...... composition of the extracted chromosome fraction. Cloning, fluorescent tagging and expression in HeLa cells of the putative GTP-binding protein NGB/CRFG demonstrated it to be a novel mitotic chromosome protein, with a perichromosomal localisation. Identi fication of the protein bands corresponding to those...

  4. The politics of protection: aid, human rights discourse, and power relations in Kyaka II settlement, Uganda.

    Science.gov (United States)

    Clark-Kazak, Christina R

    2010-01-01

    This paper explores the conceptualisation and application of 'protection' by the United Nations High Commissioner (UNHCR), Ugandan government, and Congolese refugees in Kyaka II refugee settlement, Uganda. Analysing the origins and consequences of a demonstration against school fees, and drawing on other ethnographic data, it explores how different interpretations of this incident reflect different conceptions of, and approaches to, protection. Ugandan government officials viewed the demonstration as a security incident; Congolese and Ugandan adults responded with increased monitoring and 'sheltering' of children and young people; students justified the demonstration as a legitimate manifestation of their rights; while UNHCR promoted assistance and resettlement. The paper argues that prevailing protection responses, including 'sensitisation', sheltering, and resettlement, are de-contextualised from daily realities and fail to address the underlying power relations that undermine protection. It concludes with recommendations on how international refugee agencies can reorient assistance to address protection concerns in refugee contexts.

  5. The effect of 3'- methyl-N,N-dimethylaminoasobenzene and gamma rays on the serum level of deoxyribonuclease II of the rat and the isolation of deoxyribonuclease II from the human spleen

    International Nuclear Information System (INIS)

    Jansen van Rensburg, E.

    1979-01-01

    The purpose of this investigation was twofold, viz.: 1. To determine the influence of ionising radiation (physical carcinogen) on deoxyribonuclease II in serum. 2. To develop a sensitive method for determining deoxyribonuclease II, viz. a radioimmunoassay (RlA). With this object in view, the influence of a strong physical carcinogen, viz. 60 Co gamma rays, on the activity of DNase II in rat serum was studied. For comparative studies, the influence of a strong chemical carcinogen (3'-methyl-N,N-dimethylaminoasobenzene) on rat serum DNase II was determined. In addition, attempts were made to isolate, purify and characterise DNase II from human spleen. These attempts were made as the first step in the development of a RlA. The in vivo studies of the influence of 3'MeDAB over a long period (40 weeks) showed that the DNase II activity increased in the serum and liver nuclei of rats during the pre-cancer phase. This increase may, together with other parameters, be useful in the early diagnosis of liver cancer. The most important contribution of this investigation is the possible use of a serum DNase II RlA together with a battery RlAs for other indicators (biochemical) for the determination of radiation exposure in man [af

  6. Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

    Science.gov (United States)

    Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

    2016-01-01

    Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

  7. Gene expression profiling associated with angiotensin II type 2 receptor-induced apoptosis in human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Nana Pei

    Full Text Available Increased expression of angiotensin II type 2 receptor (AT2R induces apoptosis in numerous tumor cell lines, with either Angiotensin II-dependent or Angiotensin II-independent regulation, but its molecular mechanism remains poorly understood. Here, we used PCR Array analysis to determine the gene and microRNA expression profiles in human prostate cancer cell lines transduced with AT2R recombinant adenovirus. Our results demonstrated that AT2R over expression leads to up-regulation of 6 apoptosis-related genes (TRAIL-R2, BAG3, BNIPI, HRK, Gadd45a, TP53BP2, 2 cytokine genes (IL6 and IL8 and 1 microRNA, and down-regulation of 1 apoptosis-related gene TNFSF10 and 2 cytokine genes (BMP6, BMP7 in transduced DU145 cells. HRK was identified as an up-regulated gene in AT2R-transduced PC-3 cells by real-time RT-PCR. Next, we utilized siRNAs to silence the up-regulated genes to further determine their roles on AT2R overexpression mediated apoptosis. The results showed downregulation of Gadd45a reduced the apoptotic effect by ∼30% in DU145 cells, downregulation of HRK reduced AT2R-mediated apoptosis by more than 50% in PC-3 cells, while downregulation of TRAIL-R2 enhanced AT2R-mediated apoptosis more than 4 times in DU145 cells. We also found that the effects on AT2R-mediated apoptosis caused by downregulation of Gadd45a, TRAIL-R2 and HRK were independent in activation of p38 MAPK, p44/42 MAPK and p53. Taken together, our results demonstrated that TRAIL-R2, Gadd45a and HRK may be novel target genes for further study of the mechanism of AT2R-mediated apoptosis in prostate cancer cells.

  8. Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

    1980-07-01

    High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

  9. Morphological analysis of the hindlimb in apes and humans. II. Moment arms

    Science.gov (United States)

    Payne, R C; Crompton, R H; Isler, K; Savage, R; Vereecke, E E; Günther, M M; Thorpe, S K S; D'Août, K

    2006-01-01

    Flexion/extension moment arms were obtained for the major muscles crossing the hip, knee and ankle joints in the orang-utan, gibbon, gorilla (Eastern and Western lowland) and bonobo. Moment arms varied with joint motion and were generally longer in proximal limb muscles than distal limb muscles. The shape of the moment arm curves (i.e. the plots of moment arm against joint angle) differed in different hindlimb muscles and in the same muscle in different subjects (both in the same and in different ape species). Most moment arms increased with increasing joint flexion, a finding which may be understood in the context of the employment of flexed postures by most non-human apes (except orang-utans) during both terrestrial and arboreal locomotion. When compared with humans, non-human great apes tended to have muscles better designed for moving the joints through large ranges. This was particularly true of the pedal digital flexors in orang-utans. In gibbons, the only lesser ape studied here, many of the moment arms measured were relatively short compared with those of great apes. This study was performed on a small sample of apes and thus differences noted here warrant further investigation in larger populations. PMID:16761974

  10. Study on the interaction of a copper(II) complex containing the artificial sweetener aspartame with human serum albumin.

    Science.gov (United States)

    Shahabadi, Nahid; Khodaei, Mohammad Mehdi; Kashanian, Soheila; Kheirdoosh, Fahimeh; Filli, Soraya Moradi

    2014-05-01

    A copper(II) complex containing aspartame (APM) as ligand, Cu(APM)2Cl2·2H2O, was synthesized and characterized. In vitro binding interaction of this complex with human serum albumin (HSA) was studied at physiological pH. Binding studies of this complex with HSA are useful for understanding the Cu(APM)2Cl2·2H2O-HSA interaction mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners drive. The interaction was investigated by spectrophotometric, spectrofluorometric, competition experiment and circular dichroism. Hyperchromicity observed in UV absorption band of Cu(APM)2Cl2·2H2O. A strong fluorescence quenching reaction of HSA to Cu(APM)2Cl2·2H2O was observed and the binding constant (Kf) and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy change (∆H) and entropy change (∆S) were calculated to be -458.67 kJ mol(-1) and -1,339 J mol(-1 )K(-1) respectively. According to the van't Hoff equation, the reaction is predominantly enthalpically driven. In conformity with experimental results, we suggest that Cu(APM)2Cl2·2H2O interacts with HSA. In comparison with previous study, it is found that the Cu(II) complex binds stronger than aspartame.

  11. Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

    Directory of Open Access Journals (Sweden)

    Feuer Gerold

    2004-11-01

    Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

  12. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin...

  13. A plasmid containing the human metallothionein II gene can function as an antibody-assisted electrophoretic biosensor for heavy metals.

    Science.gov (United States)

    Wooten, Dennis C; Starr, Clarise R; Lyon, Wanda J

    2016-01-01

    Different forms of heavy metals affect biochemical systems in characteristic ways that cannot be detected with typical metal analysis methods like atomic absorption spectrometry. Further, using living systems to analyze interaction of heavy metals with biochemical systems can be laborious and unreliable. To generate a reliable easy-to-use biologically-based biosensor system, the entire human metallothionein-II (MT-II) gene was incorporated into a plasmid (pUC57-MT) easily replicated in Escherichia coli. In this system, a commercial polyclonal antibody raised against human metal-responsive transcription factor-1 protein (MTF-1 protein) could modify the electrophoretic migration patterns (i.e. cause specific decreases in agarose gel electrophoretic mobility) of the plasmid in the presence or absence of heavy metals other than zinc (Zn). In the study here, heavy metals, MTF-1 protein, and polyclonal anti-MTF-1 antibody were used to assess pUC57-MT plasmid antibody-assisted electrophoretic mobility. Anti-MTF-1 antibody bound both MTF-1 protein and pUC57-MT plasmid in a non-competitive fashion such that it could be used to differentiate specific heavy metal binding. The results showed that antibody-inhibited plasmid migration was heavy metal level-dependent. Zinc caused a unique mobility shift pattern opposite to that of other metals tested, i.e. Zn blocked the antibody ability to inhibit plasmid migration, despite a greatly increased affinity for DNA by the antibody when Zn was present. The Zn effect was reversed/modified by adding MTF-1 protein. Additionally, antibody inhibition of plasmid mobility was resistant to heat pre-treatment and trypsinization, indicating absence of residual DNA extraction-resistant bacterial DNA binding proteins. DNA binding by anti-DNA antibodies may be commonly enhanced by xenobiotic heavy metals and elevated levels of Zn, thus making them potentially effective tools for assessment of heavy metal bioavailability in aqueous solutions and

  14. Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

    Science.gov (United States)

    Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

    2016-01-01

    Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

  15. Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

    Science.gov (United States)

    Schmidt, Anke; Dietrich, Stephan; Steuer, Anna; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Masur, Kai; Wende, Kristian

    2015-01-01

    Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. PMID:25589789

  16. Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays

    DEFF Research Database (Denmark)

    Preisler, Sarah Nørgaard; Rebolj, Matejka; Ejegod, Ditte Møller

    2016-01-01

    evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed...... no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. Methods Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested...... with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. Results Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3...

  17. Application of a new ultra-microculture system. II. Stimulation of human B lymphocytes.

    Science.gov (United States)

    Ulmer, A J; Gruber, M; Flad, H D

    1988-07-22

    An ultra-microtechnique for culturing human B-lymphocytes in glass capillary tubes using a volume of 2 microliter is described. The advantage of this ultra-microculture system is that only a small number of lymphocytes and minute amounts of culture medium (or test factors) are required. Optimal culture conditions for the formation of Ig-secreting plaque-forming cells (PFC) after stimulation of mononuclear cells with pokeweed mitogen are given. Furthermore it is shown that immunoglobulin secreted into culture supernatants by purified B cells in the presence of T cell subsets can be measured in a microELISA.

  18. Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

    Science.gov (United States)

    Yang, S W; Becker, F F; Chan, J Y

    1990-10-25

    DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel

  19. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects.

    Science.gov (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Ansari, A A; Bias, W B; Marsh, D G

    1988-04-01

    Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

  20. Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22phox expression

    International Nuclear Information System (INIS)

    Wang, Chaoyun; He, Yanhao; Yang, Ming; Sun, Hongliu; Zhang, Shuping; Wang, Chunhua

    2013-01-01

    Intracellular reactive oxygen species (ROS) are derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Angiotensin II (Ang II) can cause endothelial dysfunction by promoting intracellular ROS generation. Safflor yellow B (SYB) effectively inhibits ROS generation by upregulating Bcl-2 expression. In this study, we examined the effects of SYB on Ang II-induced injury to human umbilical vein endothelial cells (HUVECs), and elucidated the roles of NADPH oxidase and Bcl-2. We treated cultured HUVECs with Ang II, SYB, and Bcl-2 siRNA, and determined NADPH oxidase activity and ROS levels. Furthermore, cellular and mitochondrial physiological states were evaluated, and the expression levels of target proteins were analyzed. Ang II significantly enhanced intracellular ROS levels, caused mitochondrial membrane dysfunction, and decreased cell viability, leading to apoptosis. This was associated with increased expression of AT1R and p22 phox , increased NADPH oxidase activity, and an increased ratio of Bax/Bcl-2, leading to decreases in antioxidant enzyme activities, which were further strengthened after blocking Bcl-2. Compared to Ang II treatment alone, co-treatment with SYB significantly reversed HUVEC injury. Taken together, these results demonstrate that SYB could significantly protect endothelial cells from Ang II-induced cell damage, and that it does so by upregulating Bcl-2 expression and inhibiting ROS generation. - Highlights: • Angiotensin II depresses mitochondria physiological function. • Angiotensin II activates NADPH oxidase via up-regulating expresion of p22 phox . • Bcl-2 plays a pivotal role in improving mitochondria function and regulates ROS level. • Inhibitor of Bcl-2 promotes angiotensin II mediated HUVEC injury. • SYB attenuates angiotensin II mediated HUVEC injury via up regulating Bcl-2 expression

  1. Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

    Science.gov (United States)

    Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

    2016-01-01

    During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

  2. Ultraviolet-induced DNA excision repair in human B and T lymphocytes. II

    International Nuclear Information System (INIS)

    Yew, F.F.-H.; Johnson, R.T.

    1979-01-01

    Despite their great sensitivity to ultraviolet light purified human B and T lymphocytes are capable of complete repair provided that the ultraviolet dose does not exceed 0.5 Jm -2 . Their capacity to repair, as measured by the restoration of DNA supercoiling in preparations of nucleoids, and their survival are significantly increased in the presence of deoxyribonucleosides. Certain agents which inhibit semi-conservative DNA synthesis (hydroxyurea, 1-β-D-arabino-furanosylcytosine (arafCyt) either stop or delay the repair process in lymphocytes. The effect of hydroxyurea is eventually overcome spontaneously, but changes in the sedimentation behaviour of ultraviolet-irradiated nucleoids caused by arafCyt can only be neutralized by addition of deoxycytidine. The effective inhibition of repair by arafCyt permits the detection of extremely small amounts of ultraviolet damage and also the estimation of when repair is complete. (Auth.)

  3. The Ecology of Human-Machine Systems II: Mediating 'Direct Perception' in Complex Work Domains

    DEFF Research Database (Denmark)

    Vicente, Kim J.; Rasmussen, Jens

    1990-01-01

    Recently, a new class of artifacts has appeared in our environment: complex, high-technology work domains. An important characteristic of such systems is that their goal-relevant properties cannot be directly observed by the unaided eye. As a result, interface design is a ubiquitous problem in th...... in the design of these work environments. Nevertheless, the problem is one that has yet to be addressed in an adequate manner. An analogy to human perceptual mechanisms suggests that a smart instrument approach to interface design is needed to supplant the rote instrument (single......-sensor-single-indicator) approach that has dominated to this point. Ecological interface design (ED) is a theoretical framework in the smart instrument vein that postulates a set of general, prescriptive principles for design. The goal of E D is twofold: first, to reveal the affordances of the work domain through the interface...

  4. Population and prehistory II: space-limited human populations in constant environments.

    Science.gov (United States)

    Puleston, Cedric O; Tuljapurkar, Shripad

    2008-09-01

    We present a population model to examine the forces that determined the quality and quantity of human life in early agricultural societies where cultivable area is limited. The model is driven by the non-linear and interdependent relationships between the age distribution of a population, its behavior and technology, and the nature of its environment. The common currency in the model is the production of food, on which age-specific rates of birth and death depend. There is a single non-trivial equilibrium population at which productivity balances caloric needs. One of the most powerful controls on equilibrium hunger level is fertility control. Gains against hunger are accompanied by decreases in population size. Increasing worker productivity does increase equilibrium population size but does not improve welfare at equilibrium. As a case study we apply the model to the population of a Polynesian valley before European contact.

  5. Functional brain mapping using H215O positron emission tomography (II): mapping of human working memory

    International Nuclear Information System (INIS)

    Lee, Jae Sung; Lee, Dong Soo; Lee, Sang Kun; Nam, Hyun Woo; Kim, Seok Ki; Park, Kwang Suk; Jeong, Jae Min; Chung, June Key; Lee, Myung Chul

    1998-01-01

    To localize and compare the neural basis of verbal and visual human working memory, we performed functional activation study using H 2 15 O PET. Repeated H 2 15 O PET scans with one control and three different activation tasks were performed on six right-handed normal volunteers. Each activation task was composed of 13 matching trials. On each trial, four targets, a fixation dot and a prove were presented sequentially and subject's tasks was to press a response button to indicate whether or not the prove was one of the previous targets. Short meaningful Korean words, simple drawings and monochromic pictures of human faces were used as matching objects for verbal or visual memory. All the images were spatially normalized and the differences between control and activation states were statistically analyzed using SPM96. Statistical analysis of verbal memory activation with short words showed activation in the left Broca's area, premotor cortex, cerebellum and right cingulate gyrus. In verbal memory with simple drawing, activation was shown in the larger regions including where activated with short words and left superior temporal cortex, basal ganglia, thalamus, prefrontal cortex, anterior portion of right superior temporal gyrus and right infero-lateral frontal cortex. On the other hand, the visual memory task activated predominantly right-sided structures, especially inferior frontal cortex, supplementary motor cortex and superior parietal cortex. The results are consistent with the hypothesis of the laterality and dissociation of the verbal and visual working memory from the invasive electrophysiological studies and emphasize the pivotal role of frontal cortex and cingulate gyrus in working memory system

  6. The intestinal absorption of dietary cholesterol by hypercholesterolemic (type II) and normocholesterolemic humans.

    Science.gov (United States)

    Connor, W E; Lin, D S

    1974-04-01

    The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia. To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat. Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast. In some instances [1alpha-(3)H]cholesterol was the radioactive marker. The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol. The amount of absorbed and reexcreted labeled cholesterol proved negligible. Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days. Plasma specific activity curves were usually maximal at 48 h. Normal subjects absorbed 44.5+/-9.3 (SD) of the administered cholesterol (range 25.9-60.3). Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 47.6+/-12.6% (range 29.3-67.3). Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (42.1+/-9.3 vs. 48.9+/-9.8%). Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk. At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered. Cholesterol absorption was 42.3+/-6.0% and 45.4+/-8.3% for the two dietary periods, respectively. The absolute cholesterol absorption was linearly

  7. [PHEMA/PEI]–Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Bakhshpour, Monireh; Derazshamshir, Ali; Bereli, Nilay [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey); Elkak, Assem [Laboratory of “Valorisation des Ressources Naturelles et Produits de Santé (VRNPS)”, Doctoral School of Sciences and Technology, Lebanese University, Rafic Hariri University Campus, Hadath (Lebanon); Denizli, Adil, E-mail: denizli@hacettepe.edu [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey)

    2016-04-01

    The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]–Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH 7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]–Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). - Highlights: • Cu(II)-ions were coupled to PHEMA using PEI as the chelating ligand. • Cu(II) chelated [PHEMA/PEI] cryogels for IgG separation were produced. • Maximum IgG adsorption capacity

  8. [PHEMA/PEI]–Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma

    International Nuclear Information System (INIS)

    Bakhshpour, Monireh; Derazshamshir, Ali; Bereli, Nilay; Elkak, Assem; Denizli, Adil

    2016-01-01

    The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]–Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH 7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]–Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). - Highlights: • Cu(II)-ions were coupled to PHEMA using PEI as the chelating ligand. • Cu(II) chelated [PHEMA/PEI] cryogels for IgG separation were produced. • Maximum IgG adsorption capacity

  9. Long-term effects of prenatal x-ray of human females. II. Growth and development.

    Science.gov (United States)

    Meyer, M B; Tonascia, J

    1981-09-01

    Experimental studies and studies of survivors of in-utero exposure to atomic bomb blasts have shown significant stunting of growth and mental retardation following these exposures. Central nervous system damage following very low doses of x-ray at around the time of birth has also been observed in experimental animals. This long term follow-up studies of 1458 human females exposed in utero to diagnostic x-rays and of 1458 matched unexposed controls studied in Baltimore, Maryland, included measurements of height, weight and school achievement. Women who had been exposed to x-rays in utero were significantly shorter in their mid-twenties than were their matched, unexposed controls, even after adjustment for other social and economic factors. However, additional follow-up revealed that mothers of exposed women were also shorter than the control mothers. Short stature appeared to be a selective factor for x-ray during pregnancy (mostly pelvimetry, 1947-1952). Mothers' and daughters' heights were similarly correctly among exposed and control mother-daughter pairs, suggesting that the height differences between exposed daughters and their controls were due to these selective factor rather than to any direct effect of radiation on growth. Exposed women reported poorer school achievement than control women. However, except for a higher proportion of exposed women leaving school because of pregnancy, these measurements were no longer significantly different when rates were simultaneously adjusted for socioeconomic differences between exposed and control women.

  10. Selective attention reduces physiological noise in the external ear canals of humans. II: Visual attention

    Science.gov (United States)

    Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis

    2014-01-01

    Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention. PMID:24732070

  11. Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

    Science.gov (United States)

    Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

    1994-01-01

    The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

  12. Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3- 3 H]glucose and a marker for gluconeogenesis, [U- 14 C]lactate or sodium [ 14 C]bicarbonate [ 14 C]bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6- 3 H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [ 14 C]glucose production or for dilution of 14 C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U- 14 C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [ 14 C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U- 14 C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [ 14 C]bicarbonate as tracer (P less than 0.05, vs. [ 14 C]-lactate as tracer). When [2- 14 C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14 CO 2 is a potentially useful marker for the gluconeogenetic process in vivo

  13. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

    Energy Technology Data Exchange (ETDEWEB)

    Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

    2017-07-15

    The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

  14. Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

    International Nuclear Information System (INIS)

    Tomkinson, B.; Jonsson, A-K

    1991-01-01

    Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

  15. Analyzing the 3D Structure of Human Carbonic Anhydrase II and Its Mutants Using Deep View and the Protein Data Bank

    Science.gov (United States)

    Ship, Noam J.; Zamble, Deborah B.

    2005-01-01

    The self directed study of a 3D image of a biomolecule stresses the complex nature of the intra- and intermolecular interactions that come together to define its structure. This is made up of a series of in vitro experiments with a wild-type and mutants forms of human carbonic anhydrase II (hCAII) that examine the structure function relationship…

  16. Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

    NARCIS (Netherlands)

    van den Hoek, J. A.; Al, E. J.; Huisman, J. G.; Goudsmit, J.; Coutinho, R. A.

    1991-01-01

    The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three

  17. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS related complex, a phase I/II study

    NARCIS (Netherlands)

    van der Wouw, P. A.; van Leeuwen, R.; van Oers, R. H.; Lange, J. M.; Danner, S. A.

    1991-01-01

    Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II

  18. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  19. Relative frequency of Human T-cell Lymphotropic Virus I/II in HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Mohsen Meidani

    2014-01-01

    Conclusion: In our survey, relative frequency of HTLV-I/II was 1.8% in HIV+ patients. This study reveals that relative frequency of HTLV-I/II in HIV positive patients is considerable but determining the need for screening of HTLV-I/II requires further investigation.

  20. Soil physical degradation by human activities in the zone II of the basin of Burgos, Tamaulipas, Mexico

    International Nuclear Information System (INIS)

    Arias Mino, F.; Espinosa Rmirez, M.; Andrade Limas, E.; Castro Meza, B.; Romero Diaz, A.

    2009-01-01

    The objective of this work was to characterize the physical degradation of the soil for antropic activities during the years 2007 and 2008 in the II zone of the Burgos Basin in Tamaulipas, Mexico. In this region, human action manifests itself due to activities such as agriculture, livestock and industry. The conventional farming, based mainly on the cultivation of sorghum, is characterized by great mechanization and tilling the soil which has contributed in large measure to aggravate erosion processes. There is also some logging, mainly for charcoal production and, recently, has joined the exploration and exploitation of natural gas. We used the methodology for Assessment of Soil Degradation (ASSOD) to identify, located and define the types of soil degradation within physiographic units. Results showed that nearly 74% of the study area presents some kind of degradation. The main process was water erosion, followed, by compaction and wind erosion. The main factors are essentially overgrazing and inadequate farming practices. Approximately 60% of the units evaluated presented a moderate level of degradation, but the speed of this process indicates that maintenance works are needed to reverse. (Author) 7 refs.

  1. Downregulation of Type II Diabetes Mellitus and Maturity Onset Diabetes of Young Pathways in Human Pancreatic Islets from Hyperglycemic Donors

    Directory of Open Access Journals (Sweden)

    Jalal Taneera

    2014-01-01

    Full Text Available Although several molecular pathways have been linked to type 2 diabetes (T2D pathogenesis, it is uncertain which pathway has the most implication on the disease. Changes in the expression of an entire pathway might be more important for disease pathogenesis than changes in the expression of individual genes. To identify the molecular alterations in T2D, DNA microarrays of human pancreatic islets from donors with hyperglycemia n=20 and normoglycemia n=58 were subjected to Gene Set Enrichment Analysis (GSEA. About 178 KEGG pathways were investigated for gene expression changes between hyperglycemic donors compared to normoglycemic. Pathway enrichment analysis showed that type II diabetes mellitus (T2DM and maturity onset diabetes of the young (MODY pathways are downregulated in hyperglycemic donors, while proteasome and spliceosome pathways are upregulated. The mean centroid of gene expression of T2DM and MODY pathways was shown to be associated positively with insulin secretion and negatively with HbA1c level. To conclude, downregulation of T2DM and MODY pathways is involved in islet function and might be involved in T2D. Also, the study demonstrates that gene expression profiles from pancreatic islets can reveal some of the biological processes related to regulation of glucose hemostats and diabetes pathogenesis.

  2. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  3. Regulation of hypoxia-inducible factor-1α (HIF-1α expression by interleukin-1β (IL-1 β, insulin-like growth factors I (IGF-I and II (IGF-II in human osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Angelica Rossi Sartori-Cintra

    2012-01-01

    Full Text Available OBJECTIVE: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α can regulate cytokines (catabolic action and/or growth factors (anabolic action in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β and insulin-like growth factors I (IGF-I and II (IGF-II and to determine the involvement of the phosphatidylinositol-3kinase (PI-3K pathway in this process. METHODS: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. RESULTS: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.

  4. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...... a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...

  5. Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing.

    Science.gov (United States)

    Dong, De-Li; Chen, Chang; Huang, Wei; Chen, Yan; Zhang, Xiao-Lan; Li, Zhe; Li, Yue; Yang, Bao-Feng

    2008-08-20

    Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present study was to characterize the CORM2-induced current and to access the relation with CO releasing. CORM2 (100 microM) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 microM), La(3+) (10 microM) or 2-aminoethoxydiphenyl borate (100 microM). CO (10 microM), CORM3 (100, 200 microM) and RuCl(3) (100 microM) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing.

  6. Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study.

    Science.gov (United States)

    Muhonen, Virpi; Salonius, Eve; Haaparanta, Anne-Marie; Järvinen, Elina; Paatela, Teemu; Meller, Anna; Hannula, Markus; Björkman, Mimmi; Pyhältö, Tuomo; Ellä, Ville; Vasara, Anna; Töyräs, Juha; Kellomäki, Minna; Kiviranta, Ilkka

    2016-05-01

    The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n = 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:745-753, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. Trans- and cis-2-phenylindole platinum(II) complexes as cytotoxic agents against human breast adenocarcinoma cell lines

    Science.gov (United States)

    Tomé, Maria; López, Concepción; González, Asensio; Ozay, Bahadir; Quirante, Josefina; Font-Bardía, Mercè; Calvet, Teresa; Calvis, Carme; Messeguer, Ramon; Baldomá, Laura; Badía, Josefa

    2013-09-01

    The synthesis and characterization of the new 2-phenylindole derivative: C8H3N-2-C6H5-3NOMe-5OMe (3c) and the trans- and cis-isomers of [Pt(3c)Cl2(DMSO)] complexes (4c and 5c, respectively) are described. The crystal structures of 4c·CH2Cl2 and 5c confirm: (a) the existence of a Pt-Nindole bond, (b) the relative arrangement of the Cl- ligands [trans- (in 4c) or cis- (in 5c)] and (c) the anti-(E) configuration of the oxime. The cytotoxic assessment of C8H3N-2-(C6H4-4‧R1)-3NOMe-5R2 [with R1 = R2 = H (3a); R1 = Cl, R2 = H (3b) and R1 = H, R2 = OMe (3c)] and the geometrical isomers of [Pt(L)Cl2(DMSO)] with L = 3a-3c [trans- (4a-4c) and cis- (5a-5c), respectively] against human breast adenocarcinoma cell lines (MDA-MB231 and MCF-7) is also reported and reveals that all the platinum(II) complexes (except 4a) are more cytotoxic than cisplatin in front of the MCF7 cell line. Electrophoretic DNA migration studies of the synthesized compounds in the absence and in the presence of topoisomerase-I have been performed, in order to get further insights into their mechanism of action.

  8. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S.; Krause, T.; van Geel, P. P.; Willenbrock, R.; Pagel, I.; Pinto, Y. M.; Buikema, H.; van Gilst, W. H.; Lindschau, C.; Paul, M.; Inagami, T.; Ganten, D.; Urata, H.

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  9. Overexpression of the human angiotensin II type 1 receptor in the rat heart augments load induced cardiac hypertrophy

    NARCIS (Netherlands)

    Hoffmann, S; van Geel, PP; Willenbrock, R; Pagel, [No Value; Pinto, YM; Buikema, H; van Gilst, WH; Lindschau, C; Paul, M; Inagami, T; Ganten, D; Urata, H

    2001-01-01

    Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT(1) receptors. However, the role of myocardial AT(1) receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that

  10. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  11. SLIM-MAUD: an approach to assessing human error probabilities using structured expert judgment. Volume II. Detailed analysis of the technical issues

    International Nuclear Information System (INIS)

    Embrey, D.E.; Humphreys, P.; Rosa, E.A.; Kirwan, B.; Rea, K.

    1984-07-01

    This two-volume report presents the procedures and analyses performed in developing an approach for structuring expert judgments to estimate human error probabilities. Volume I presents an overview of work performed in developing the approach: SLIM-MAUD (Success Likelihood Index Methodology, implemented through the use of an interactive computer program called MAUD-Multi-Attribute Utility Decomposition). Volume II provides a more detailed analysis of the technical issues underlying the approach

  12. Type II cGMP‑dependent protein kinase inhibits the migration, invasion and proliferation of several types of human cancer cells.

    Science.gov (United States)

    Wu, Min; Wu, Yan; Qian, Hai; Tao, Yan; Pang, Ji; Wang, Ying; Chen, Yongchang

    2017-10-01

    Previous studies have indicated that type II cyclic guanosine monophosphate (cGMP)‑dependent protein kinase (PKG II) could inhibit the proliferation and migration of gastric cancer cells. However, the effects of PKG II on the biological functions of other types of cancer cells remain to be elucidated. Therefore, the aim of the present study was to investigate the effects of PKG II on cancer cells derived from various types of human tissues, including A549 lung, HepG2 hepatic, OS‑RC‑2 renal, SW480 colon cancer cells and U251 glioma cells. Cancer cells were infected with adenoviral constructs coding PKG II (Ad‑PKG II) to up‑regulate PKG II expression, and treated with 8‑(4‑chlorophenylthio) (8‑pCPT)‑cGMP to activate the kinase. A Cell Counting kit 8 assay was used to detect cell proliferation. Cell migration was measured using a Transwell assay, whereas a terminal deoxynucleotidyl transferase 2'‑deoxyuridine, 5'‑triphosphate nick‑end labeling assay was used to detect cell apoptosis. A pull‑down assay was used to investigate the activation of Ras‑related C3 botulinum toxin substrate (Rac) 1 and western blotting was used to detect the expression of proteins of interest. The present results demonstrated that EGF (100 ng/ml, 24 h) promoted the proliferation and migration of cancer cells, and it suppressed their apoptosis. In addition, treatment with EGF enhanced the activation of Rac1, and up‑regulated the protein expression of proliferating cell nuclear antigen, matrix metalloproteinase (MMP)2, MMP7 and B‑cell lymphoma (Bcl)‑2, whereas it down‑regulated the expression of Bcl‑2‑associated X protein. Transfection of cancer cells with Ad‑PKG II, and PKG II activation with 8‑pCPT‑cGMP, was identified to counteract the effects triggered by EGF. The present results suggested that PKG II may exert inhibitory effects on the proliferation and migration of various types of cancer cells.

  13. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

  14. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

    NARCIS (Netherlands)

    A.G.A. Bijvoet (Agnes); A.J.J. Reuser (Arnold); H. van Hirtum (Hans); M.A. Kroos (Marian); E.H. van de Kamp; O. Schoneveld; P. Visser (Pim); J.P. Brakenhoff (Just); M. Weggeman (Miranda); E.J.J.M. van Corven (Emiel); A.T. van der Ploeg (Ans)

    1999-01-01

    textabstractPompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal

  15. Human leukocyte antigen class I and II alleles and cervical adenocarcinoma: a pooled analysis of two epidemiologic studies

    Directory of Open Access Journals (Sweden)

    Mahboobeh eSafaeian

    2014-06-01

    Full Text Available Associations between human leukocyte antigens (HLA alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC, the major histologic subtype. We evaluated the association between HLA class I (A, B, and C and class II (DRB1 and DQB1 loci and risk of cervical adenocarcinoma (ADC, a less common but aggressive histologic subtype.We pooled data from the Eastern and Western US cervical cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n=630 ADC; n=775 controls. Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type and 38 non a priori common alleles, as odds ratios (OR and 95% confidence intervals (CI, adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls. Three of the a priori alleles were significantly associated with decreased risk of ADC (DRB1*13:01 (OR=0.61; 95%CI:0.41-0.93, DRB1*13:02 (OR=0.49; 95%CI:0.31-0.77, and DQB1*06:03 (OR=0.64; 95%CI:0.42-0.95; one was associated with increased risk (B*07:02(OR=1.39; 95%CI:1.07-1.79. Among alleles not previously reported, DQB1*06:04 (OR=0.46; 95%CI: 0.27-0.78 was associated with decreased risk of ADC and C*07:02 (OR=1.41; 95%CI:1.09-1.81 was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR=1.33; 95%CI:1.01-1.76 and decreased risk with DRB1*13:02/DQB1*06:04 (OR=0.41; 95%CI:0.21-0.80. Results suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18 related tumors, consistent with the hypothesis that HLA recognition is HPV type specific.

  16. Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.

    Science.gov (United States)

    Dutta, Shovan; Celestine, Michael J; Khanal, Supreet; Huddleston, Alexis; Simms, Colin; Arca, Jessa Faye; Mitra, Amlan; Heller, Loree; Kraj, Piotr J; Ledizet, Michel; Anderson, John F; Neelakanta, Girish; Holder, Alvin A; Sultana, Hameeda

    2018-01-01

    Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100μM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen) 2 ]Cl 2 , (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen) 3 ]Cl 3 , (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl 2 ·2H 2 O) or cobalt(II) chloride hexahydrate (CoCl 2 ·6H 2 O) alone had no effects as "free" cations

  17. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  18. ‘Fortress Europe’: Compliance of the Dublin II Regulation with the European Convention for the Protection of Human Rights and Fundamental Freedoms

    Directory of Open Access Journals (Sweden)

    Joanna Lenart

    2012-06-01

    Full Text Available Recently, the Dublin II Regulation, a cornerstone of the emerging Common European Asylum System, has been gravely criticised, especially in context of the living conditions and general situation of asylum seekers in Greece. The main concerns regard the potential noncompliance of the Dublin II Regulation with the European Convention on Human Rights ('ECHR', particularly with Article 3 - the prohibition of torture or inhuman or degrading treatment. This article examines the competing views in this respect. It analyses the relationship between EU law and the ECHR, protection of rights of refugees under the 1951 Convention relating to the Status of Refugees and main deficiencies of the Dublin II Regulation. The analysis starts with the non-equivalent protection of asylum seekers throughout the EU and finishes with the very limited definition of a family member and case law relevant to the principle of non-refoulement. This article concludes that the Dublin II Regulation per se cannot be deemed noncompliant with the ECHR. However, it emphasises the urgent need to change relevant legal provisions, or at least enforcement, and proposes possible solutions therein.

  19. Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vandenberg, P.; Khillan, J.S.; Prockop, D.J.; Helminen, H.; Kontusaari, S.; Ala-Kokko, L. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1991-09-01

    A minigene version of the human gene for type II procollagen (COL2AI) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro{alpha} chains that associate with normal pro{alpha} chains and thereby cause degradation of the shortened and normal pro{alpha} chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing the minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro{alpha}1(II) chains that were disulfide-linked to normal mouse pro{alpha}1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide.

  20. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis.

    Science.gov (United States)

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio

    2016-06-20

    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  1. Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y.

    Science.gov (United States)

    Tosi, Giovanna; Pilotti, Elisabetta; Mortara, Lorenzo; De Lerma Barbaro, Andrea; Casoli, Claudio; Accolla, Roberto S

    2006-08-22

    The master regulator of MHC-II gene transcription, class II transactivator (CIITA), acts as a potent inhibitor of human T cell leukemia virus type 2 (HTLV-2) replication by blocking the activity of the viral Tax-2 transactivator. Here, we show that this inhibitory effect takes place at the nuclear level and maps to the N-terminal 1-321 region of CIITA, where we identified a minimal domain, from positions 64-144, that is strictly required to suppress Tax-2 function. Furthermore, we show that Tax-2 specifically cooperates with cAMP response element binding protein-binding protein (CBP) and p300, but not with p300/CBP-associated factor, to enhance transcription from the viral promoter. This finding represents a unique difference with respect to Tax-1, which uses all three coactivators to transactivate the human T cell leukemia virus type 1 LTR. Direct sequestering of CBP or p300 is not the primary mechanism by which CIITA causes suppression of Tax-2. Interestingly, we found that the transcription factor nuclear factor Y, which interacts with CIITA to increase transcription of MHC-II genes, exerts a negative regulatory action on the Tax-2-mediated HTLV-2 LTR transactivation. Thus, CIITA may inhibit Tax-2 function, at least in part, through nuclear factor Y. These findings demonstrate the dual defensive role of CIITA against pathogens: it increases the antigen-presenting function for viral determinants and suppresses HTLV-2 replication in infected cells.

  2. Crystallization and preliminary X-ray analysis of the complexes between a Fab and two forms of human insulin-like growth factor II

    International Nuclear Information System (INIS)

    Newman, Janet; Cohen, Edward H.; Cosgrove, Leah; Kopacz, Kris; Dransfield, Daniel T.; Adams, Timothy E.; Peat, Thomas S.

    2009-01-01

    Complexes of both hIGF-II and hIGF-IIE with a Fab have been crystallized and investigated by X-ray analysis. Elevated expression of insulin-like growth factor II (IGF-II) is frequently observed in a variety of human malignancies, including breast, colon and liver cancer. As IGF-II can deliver a mitogenic signal through both the type 1 insulin-like growth factor receptor (IGF-IR) and an alternately spliced form of the insulin receptor (IR-A), neutralizing the biological activity of this growth factor directly is an attractive therapeutic option. One method of doing this would be to find antibodies that bind tightly and specifically to the peptide, which could be used as protein therapeutics to lower the peptide levels in vivo and/or to block the peptide from binding to the IGF-IR or IR-A. To address this, Fabs were selected from a phage-display library using a biotinylated precursor form of the growth factor known as IGF-IIE as a target. Fabs were isolated that were specific for the E-domain C-terminal extension and for mature IGF-II. Four Fabs selected from the library were produced, complexed with IGF-II and set up in crystallization trials. One of the Fab–IGF-II complexes (M64-F02–IGF-II) crystallized readily, yielding crystals that diffracted to 2.2 Å resolution and belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.7, b = 106.9, c = 110.7 Å. There was one molecule of the complete complex in the asymmetric unit. The same Fab was also crystallized with a longer form of the growth factor, IGF-IIE. This complex crystallized in space group P2 1 2 1 2 1 , with unit-cell parameters a = 50.7, b = 107, c = 111.5 Å, and also diffracted X-rays to 2.2 Å resolution

  3. Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency.

    Science.gov (United States)

    Wezynfeld, Nina Ewa; Bonna, Arkadiusz; Bal, Wojciech; Frączyk, Tomasz

    2015-04-01

    Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.

  4. Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.

    Science.gov (United States)

    Guimond, Marie-Odile; Battista, Marie-Claude; Nikjouitavabi, Fatemeh; Carmel, Maude; Barres, Véronique; Doueik, Alexandre A; Fazli, Ladan; Gleave, Martin; Sabbagh, Robert; Gallo-Payet, Nicole

    2013-07-01

    Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture. AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate. AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells. AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance. Copyright © 2013 Wiley Periodicals, Inc.

  5. Quercetin alters the DNA damage response in human hematopoietic stem and progenitor cells via TopoII- and PI3K-dependent mechanisms synergizing in leukemogenic rearrangements.

    Science.gov (United States)

    Biechonski, Shahar; Gourevich, Dana; Rall, Melanie; Aqaqe, Nasma; Yassin, Muhammad; Zipin-Roitman, Adi; Trakhtenbrot, Luba; Olender, Leonid; Raz, Yael; Jaffa, Ariel J; Grisaru, Dan; Wiesmuller, Lisa; Elad, David; Milyavsky, Michael

    2017-02-15

    Quercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined. In this study we describe novel and potentially genotoxic Que activities in suppressing non-homologous end joining and homologous recombination pathways downstream of MLL cleavage. Using pharmacological dissection of DNA-PK, ATM and PI3K signalling we defined PI3K inhibition by Que with a concomitant decrease in the abundance of key DNA repair genes to be responsible for DNA repair inhibition. Evidence for the downstream TopoII-independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Importantly, by engaging a tissue engineered placental barrier, we have established the extent of Que transplacental transfer and hence provided the evidence for Que reaching fetal HSPCs. Thus, Que exhibits genotoxic effects in human HSPCs via different mechanisms when applied continuously and at high concentrations. In light of the demonstrated Que transfer to the fetal compartment our findings are key to understanding the mechanisms underlying infant leukemia and provide molecular markers for the development of safety values. © 2016 UICC.

  6. Human and Organizational Issues in the Army After Next - II: A Conference Held 24-26 June 1998

    National Research Council Canada - National Science Library

    Drillings, Michael

    1998-01-01

    .... Some of the topics discussed were Future Personnel Management, Teams and Organizations, Information Technology, The Leadership Challenge, Army Science Board of Human Behavior in Combat and Strategic...

  7. 3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

    OpenAIRE

    Yamasaki, Keishi; Rahman, Mohammed Hablbur; Tsutsumi, Yasuhiro; Maruyama, Toru; Ahmed, Shamim; Kragh-Hansen; Otagiri, Masaki

    2000-01-01

    Purpose: The purpose of this study was to confirm the hypothesis that a site-II-to-site-I displacement takes place when some nonsteroidal anti-inflammatory drugs are displaced by another drug from their high-affinity binding site to a site of lower affinity on human serum albumin (HSA).Methods: Diclofenac, sodium salt, was used as a representative example because of its prominent reversal of the Cotton effect. Effects of site-specific drugs on the free fraction of diclofenac were determined b...

  8. Human Retroviruses and AIDS. A compilation and analysis of nucleic acid and amino acid sequences: I--II; III--V

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States); Wain-Hobson, S. [ed.] [Laboratory of Molecular Retrovirology, Pasteur Inst.; Smith, R.F. [ed.] [Baylor Coll. of Medicine, Houston, TX (United States). Dept. of Pharmacology; Pavlakis, G.N. [ed.] [National Cancer Inst., Frederick, MD (United States). Cancer Research Facility

    1993-12-31

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (I) HIV and SIV Nucleotide Sequences; (II) Amino Acid Sequences; (III) Analyses; (IV) Related Sequences; and (V) Database Communications. Information within all the parts is updated at least twice in each year, which accounts for the modes of binding and pagination in the compendium.

  9. Application of the human needs conceptual model of dental hygiene to the role of the clinician : part II.

    Science.gov (United States)

    Walsh, M M; Darby, M

    1993-01-01

    In summary, the theories of Maslow and of Yura and Walsh have been highlighted as background for understanding the human needs conceptual model of dental hygiene. In addition, 11 human needs have been identified and defined as being especially related to dental hygiene care, and a sample evaluation tool for their clinical assessment and a dental hygiene care plan have been presented. The four concepts of client, environment, health/oral health, and dental hygiene actions explained in terms of human need theory, and the 11 human needs related to dental hygiene care constitute the human needs conceptual model of dental hygiene. Within the framework of the human needs conceptual model of dental hygiene, the dental hygiene process is a systematic approach to dental hygiene care that involves assessment of the 11 human needs related to dental hygiene care; analysis of deficits in these needs; determination of the dental hygiene care plan based on identified deficits; implementation of dental hygiene interventions stated in the care plan; and evaluation of the effectiveness of dental hygiene interventions in achieving specific goals, including subsequent reassessment and revision of the dental hygiene care plan. This human needs conceptual model for dental hygiene provides a guide for comprehensive and humanistic client care. This model allows the dental hygienist to view each client (whether an individual or a group) holistically to prevent oral disease and to promote health and wellness. Dental hygiene theorists are encouraged to expand this model or to develop additional conceptual models based on dental hygiene's paradigm.

  10. New modulated design, docking and synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV complex as potential topoisomerase II inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines.

    Science.gov (United States)

    Tabassum, Sartaj; Afzal, Mohd; Arjmand, Farukh

    2014-03-03

    New carbohydrate-conjugate heterobimetallic complexes [C₂₂H₅₀N₆O₁₃CuSnCl₂] (3) and [C₂₂H₅₈N₆O₁₇NiSnCl₂] (4) were synthesized from their monometallic analogs [C₂₂H₅₂N₆O₁₃Cu] (1) and [C₂₂H₆₀N₆O₁₇Ni] (2) containing N-glycoside ligand (L). In vitro DNA binding studies of L and complexes (1-4) with CT DNA were carried out by employing various biophysical and molecular docking techniques which revealed that heterobimetallic complex 3 strongly binds to DNA in comparison to 4, monometallic complexes (1 and 2) and the free ligand. Complex 3 cleaves pBR322 DNA via hydrolytic pathway (confirmed by T4 DNA ligase assay) and inhibited Topo-II activity in a dose-dependent manner. Furthermore, complex 3 was docked into the ATPase domain of human-Topo-II in order to probe the possible mechanism of inhibition. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Chiral Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine and its Phase I and II Metabolites following Controlled Administration to Humans.

    OpenAIRE

    Steuer Andrea E; Schmidhauser Corina; Schmid Yasmin; Rickli Anna; Liechti Matthias E; Kraemer Thomas

    2015-01-01

    Generally, pharmacokinetic studies on 3,4-methylenedioxymethamphetamine (MDMA) in blood have been performed after conjugate cleavage, without taking into account that phase II metabolites represent distinct chemical entities with their own effects and stereoselective pharmacokinetics. The aim of the present study was to stereoselectively investigate the pharmacokinetics of intact glucuronide and sulfate metabolites of MDMA in blood plasma after a controlled single MDMA dose. Plasma samples fr...

  12. Insight into eukaryotic topoisomerase II-inhibiting fused heterocyclic compounds in human cancer cell lines by molecular docking.

    Science.gov (United States)

    Taskin, T; Yilmaz, S; Yildiz, I; Yalcin, I; Aki, E

    2012-01-01

    Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Unfortunately, its wide therapeutic application is often hindered by multidrug resistance (MDR), low water solubility and toxicity. In our previous study, new derivatives of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were synthesized and exhibited better inhibitory activity compared with the drug etoposide itself. To expose the binding interactions between the eukaryotic topoisomerase II and the active heterocyclic compounds, docking studies were performed, using the software Discovery Studio 2.1, based on the crystal structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was conducted on a selected set of 31 fused heterocyclic compounds with variation in structure and activity. The structural analyses indicate coordinate and hydrogen bonding interactions, van der Waals interactions and hydrophobic interactions between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible for the preference of inhibition and potency. Collectively, the results demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant anti-tumour drug candidates that should be further studied.

  13. Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology Os Vírus T-Linfotrópicos Humanos tipo I (HTLV-I e tipo II (HTLV-II na Guiana Francesa: epidemiologia clínica e molecular

    Directory of Open Access Journals (Sweden)

    Mirdad Kazanji

    2003-10-01

    Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.Os autores apresentam uma revisão dos estudos epidemiológicos realizados pelo seu grupo de pesquisa sobre a infecção pelos vírus T-linfotrópicos humanos tipo I (HTLV-I e tipo II (HTLV-II e doenças associadas na Guiana Francesa, desde 1984. A Guiana Francesa é um Departamento de Ultramar da França, situado entre o Brasil e o Suriname. A população é caracterizada por uma grande variedade de grupos étnicos, incluindo diversas comunidades de origem africana e outras de origem indígena. Diversos inquéritos epidemiológicos sobre gestantes e em aldeias remotas mostraram que o HTLV-I é altamente endêmico nessas áreas, mas que o vírus é restrito a grupos de origem africana, particularmente os Noir-Marrons. Nessa população endêmica, os resultados de uma an

  14. Effect of Cell Sheet Manipulation Techniques on the Expression of Collagen Type II and Stress Fiber Formation in Human Chondrocyte Sheets.

    Science.gov (United States)

    Wongin, Sopita; Waikakul, Saranatra; Chotiyarnwong, Pojchong; Siriwatwechakul, Wanwipa; Viravaidya-Pasuwat, Kwanchanok

    2018-03-01

    Cell sheet technology is applied to human articular chondrocytes to construct a tissue-like structure as an alternative treatment for cartilage defect. The effect of a gelatin manipulator, as a cell sheet transfer system, on the quality of the chondrocyte sheets was investigated. The changes of important chondrogenic markers and stress fibers, resulting from the cell sheet manipulation, were also studied. The chondrocyte cell sheets were constructed with patient-derived chondrocytes using a temperature-responsive polymer and a gelatin manipulator as a transfer carrier. The properties of the cell sheets, including sizes, expression levels of collagen type II and I, and the localization of the stress fibers, were assessed and compared with those of the cell sheets harvested without the gelatin manipulator. Using the gelatin manipulator, the original size of the chondrocyte cell sheets was retained with abundant stress fibers, but with a decrease in the expression of collagen type II. Without the gelatin manipulator, although the cell shrinkage occurred, the cell sheet with suppressed stress fiber formation showed significantly higher levels of collagen type II. These results support our observations that stress fiber formation in chondrocyte cell sheets affected the production of chondrogenic markers. These densely packed tissue-like structures possessed a good chondrogenic activity, indicating their potential for use in autologous chondrocyte implantation to treat cartilage defects.

  15. Tyrosine411 and Arginine410 of Human Serum Albumin Play an Important Role in the Binding of Sodium 4-Phenylbutyrate to Site II.

    Science.gov (United States)

    Enokida, Taisuke; Yamasaki, Keishi; Okamoto, Yuko; Taguchi, Kazuaki; Ishiguro, Takako; Maruyama, Toru; Seo, Hakaru; Otagiri, Masaki

    2016-06-01

    Sodium 4-phenylbutyrate (PB) has many pharmacological activities; therefore extending its clinical use to the treatment of a wider variety of diseases would be desirable. However, our knowledge of the binding of PB to plasma proteins is not extensive. To address this issue in more detail, we characterized the protein binding of PB. Binding experiments showed that PB mainly binds to human serum albumin (HSA) in plasma. PB was also found to bind to a single site on HSA, which was identified as site II by fluorescent probe displacement experiment. Furthermore, an appropriate alkyl chain length and a carboxylic group in the PB structure were required for PB binding to HSA, suggesting that hydrophobic (and van der Waals) and electrostatic interactions are involved as binding modes. The contributions of hydrogen bonding and/or van der Waals interactions were also indicated by thermodynamic analyses. Tyrosine411 and arginine410 were identified as being involved in the binding of PB to site II, based on binding experiments using chemically modified- and mutant-HSA preparations. In conclusion, the available evidence indicates that PB binds to site II of HSA with assistance by multiple forces and that tyrosine411 and arginine410 both play important roles in this phenomenon. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Dual Inhibition of Topoisomerase II and Tyrosine Kinases by the Novel Bis-Fluoroquinolone Chalcone-Like Derivative HMNE3 in Human Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yong-Chao Ma

    Full Text Available Both tyrosine kinase and topoisomerase II (TopII are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cellular apoptosis was determined using Hoechst 33258 fluorescence staining and the terminal deoxynucleotidyl transferase (TdT dUTP nick-end labeling (TUNEL assay. The expression of activated Caspase-3 was examined by immunocytochemistry. The tyrosine kinase activity was measured with a human receptor tyrosine kinase (RTK detection kit using a horseradish peroxidase (HRP-conjugated phosphotyrosine (pY20 antibody as the substrate. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. The expression levels of the P53, Bax, Bcl-2, Caspase-3, -8, -9, p-cSrc, c-Src and topoisomerase II proteins were detected by western blot analysis. The proliferation of five of the six cancer cell lines was significantly inhibited by HMNE3 at 0.312 to 10 μmol/L in a time- and dose-dependent manner. Treatment of the Capan-1 and Panc-1 cells with 1.6 to 3.2 μM HMNE3 for 48 h significantly increased the percentage of apoptotic cells (P<0.05, and this effect was accompanied by a decrease in tyrosine kinase activity. HMNE3 potentially inhibited tyrosine kinase activity in vitro with an IC50 value of 0.64±0.34 μmol/L in Capan-1 cells and 3.1±0.86 μmol/L in Panc-1 cells. The activity of c-Src was significantly inhibited by HMNE3 in a dose

  17. Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

    Science.gov (United States)

    Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

    2010-04-01

    We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

  18. Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

    International Nuclear Information System (INIS)

    Miyatake, Kazumasa; Tsuji, Kunikazu; Yamaga, Mika; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Muneta, Takeshi

    2013-01-01

    Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis

  19. Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

    Energy Technology Data Exchange (ETDEWEB)

    Miyatake, Kazumasa [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Tsuji, Kunikazu, E-mail: ktsuji.gcoe@tmd.ac.jp [International Research Center for Molecular Science in Tooth and Bone Diseases (Global Center of Excellence Program), Tokyo Medical and Dental University, Tokyo (Japan); Yamaga, Mika; Yamada, Jun; Matsukura, Yu; Abula, Kahaer [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); Sekiya, Ichiro [Section of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo (Japan); Muneta, Takeshi [Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Tokyo (Japan); International Research Center for Molecular Science in Tooth and Bone Diseases (Global Center of Excellence Program), Tokyo Medical and Dental University, Tokyo (Japan)

    2013-02-01

    Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.

  20. Investigation of Virtual Digital Human and Robotic Device Technology Merger Complimented by Haptics and Autostereoscopic Displays, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — As expected, the STTR Phase I investigation confirmed that the Digital Virtual Human (DVH) and Robonaut technologies can be merged, and that haptic and...

  1. Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

  2. An analysis of the human reliability on Three Mile Island II accident considering THERP and ATHEANA methodologies

    International Nuclear Information System (INIS)

    Fonseca, Renato Alves da; Alvim, Antonio Carlos Marques

    2005-01-01

    The research on the Analysis of the Human Reliability becomes more important every day, as well as the study of the human factors and the contributions of the same ones to the incidents and accidents, mainly in complex plants or of high technology. The analysis here developed it uses the methodologies THERP (Technique for Human Error Prediction) and ATHEANA (A Technique for Human Error Analysis), as well as, the tables and the cases presented in THERP Handbook and to develop a qualitative and quantitative study of an occurred nuclear accident. The chosen accident was it of Three Mile Island (TMI). The accident analysis has revealed a series of incorrect actions that resulted in the permanent loss of the reactor and shutdown of Unit 2. This study also aims at enhancing the understanding of the THERP and ATHEANA methods and at practical applications. In addition, it is possible to understand the influence of plant operational status on human failures and the influence of human failures on equipment of a system, in this case, a nuclear power plant. (author)

  3. Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-02-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

  4. Nhe I and Hinc II polymorphisms in the human laminin B1 chain gene on 7q22

    Energy Technology Data Exchange (ETDEWEB)

    Pikkarainen, T; Savolainen, E R; Tryggvason, K [Univ. of Oulu (Finland)

    1989-06-12

    pHL-40 and pHL-42 are overlapping cDNA clones that code for 4.2 kb of the 3{prime} end of the 5.5 kb mRNA. Nhe I detects a two allele polymorphism with fragments of 4.3 kb or 4.0 kb and an invariant band of 10.0 kb. Hinc II detects a two allele polymorphism with fragments of 6.6 kb or 5.5 kb and 1.1 kb and invariant bands of 7.8 kb, 4.0 kb, 3.3 kb, 2.3 kb and 0.6 kb. The allele frequency was studied in 60 chromosomes of unrelated Finnish individuals. The probe was localized to chromosome 7q22 by somatic cell and in situ hybridization. Co-dominant inheritance of the Nhe I RFLP was shown in one family and of the Hinc II RFLP in five families.

  5. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  6. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  7. Stimulation of the Angiotensin II AT2 Receptor is Anti-inflammatory in Human Lipopolysaccharide-Activated Monocytic Cells

    DEFF Research Database (Denmark)

    Menk, Mario; Graw, Jan Adriaan; von Haefen, Clarissa

    2015-01-01

    and the translational level over course of time. Treatment with C21 attenuated the expression of TNFα, IL-6, and IL-10 after LPS challenge in both cell lines in a time- and dose-dependent manner. We conclude that selective AT2 receptor stimulation acts anti-inflammatory in human monocytes. Modulation of cytokine......Recently, AT2 receptors have been discovered on the surface of human immunocompetent cells such as monocytes. Data on regulative properties of this receptor on the cellular immune response are poor. We hypothesized that direct stimulation of the AT2 receptor mediates anti-inflammatory responses...... in these cells. Human monocytic THP-1 and U937 cells were stimulated with lipopolysaccharide (LPS) and the selective AT2 receptor agonist Compound 21 (C21). Expression of pro- and anti-inflammatory cytokines IL-6, IL-10, tumor necrosis factor-α (TNFα), and IL-1β were analyzed on both the transcriptional...

  8. Why is Organizing Human Resource Development so Problematic? Perspectives from the Learning-Network Theory (Part II)

    Science.gov (United States)

    Poell, Rob F.; Van Der Krogt, Ferd

    2017-01-01

    Purpose: Human resource development (HRD) is an important field within management. Developing employees is often regarded as an instrument to improve the internal labor market and support organizational change. Organizing HRD to these ends, however, is frequently a problematic affair, in terms of training effectiveness, participant motivation and…

  9. Why is organizing human resource development so problematic? : Perspectives from the learning-network theory (Part II)

    NARCIS (Netherlands)

    Poell, R.F.; van der Krogt, F.J.

    2017-01-01

    Purpose Human resource development (HRD) is an important field within management. Developing employees is often regarded as an instrument to improve the internal labor market and support organizational change. Organizing HRD to these ends, however, is frequently a problematic affair, in terms of

  10. New experimental diffractive-optical data on E.Land's Retinex mechanism in human color vision: Part II

    Science.gov (United States)

    Lauinger, N.

    2007-09-01

    A better understanding of the color constancy mechanism in human color vision [7] can be reached through analyses of photometric data of all illuminants and patches (Mondrians or other visible objects) involved in visual experiments. In Part I [3] and in [4, 5 and 6] the integration in the human eye of the geometrical-optical imaging hardware and the diffractive-optical hardware has been described and illustrated (Fig.1). This combined hardware represents the main topic of the NAMIROS research project (nano- and micro- 3D gratings for optical sensors) [8] promoted and coordinated by Corrsys 3D Sensors AG. The hardware relevant to (photopic) human color vision can be described as a diffractive or interference-optical correlator transforming incident light into diffractive-optical RGB data and relating local RGB onto global RGB data in the near-field behind the 'inverted' human retina. The relative differences at local/global RGB interference-optical contrasts are available to photoreceptors (cones and rods) only after this optical pre-processing.

  11. Fundamental dynamic characteristics of human skull : Part II - Measurement and FE modeling of stress wave propagation after impact loading

    Czech Academy of Sciences Publication Activity Database

    Horáček, Jaromír; Trnka, Jan; Pešek, Luděk; Veselý, Eduard

    2004-01-01

    Roč. 11, č. 3 (2004), s. 177-190 ISSN 1210-2717 R&D Projects: GA ČR GV106/98/K019 Institutional research plan: CEZ:AV0Z2076919 Keywords : biomechanics of human head * bone conduction * skull FE model Subject RIV: BI - Acoustics

  12. Human Trafficking in the United States. Part II. Survey of U.S. Government Web Resources for Publications and Data

    Science.gov (United States)

    Panigabutra-Roberts, Anchalee

    2012-01-01

    This second part of a two-part series is a survey of U.S. government web resources on human trafficking in the United States, particularly of the online publications and data included on agencies' websites. Overall, the goal is to provide an introduction, an overview, and a guide on this topic for library staff to use in their research and…

  13. A Plasmid Containing the Human Metallothionein II Gene Can Function as an Antibody-assisted Electrophoretic Biosensor for Heavy Metals

    Science.gov (United States)

    2015-01-16

    Biol. Chem. 273:7127–7133. Brugnera, E., Georgiev, O., Radtke , F., et al. 1994. Cloning, chromosomal mapping and characterization of the human metal...Signaling events for metallothionein induction. Mutat. Res. 533:211–226. Heuchel, R., Radtke , F., Georgiev, O., et al. 1994. The transcription factor MTF

  14. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module II. Human Systems and Patient Assessment.

    Science.gov (United States)

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on human systems and patient assessment is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Four units are presented: (1) medical terminology, which covers some common prefixes and suffixes and the use of the medical dictionary; (2) an overview of the…

  15. Quality of Life Theory II. Quality of Life as the Realization of Life Potential: A Biological Theory of Human Being

    Directory of Open Access Journals (Sweden)

    Soren Ventegodt

    2003-01-01

    Full Text Available This review presents one of the eight theories of the quality of life (QOL used for making the SEQOL (self-evaluation of quality of life questionnaire or the quality of life as realizing life potential. This theory is strongly inspired by Maslow and the review furthermore serves as an example on how to fulfill the demand for an overall theory of life (or philosophy of life, which we believe is necessary for global and generic quality-of-life research.Whereas traditional medical science has often been inspired by mechanical models in its attempts to understand human beings, this theory takes an explicitly biological starting point. The purpose is to take a close view of life as a unique entity, which mechanical models are unable to do. This means that things considered to be beyond the individual's purely biological nature, notably the quality of life, meaning in life, and aspirations in life, are included under this wider, biological treatise. Our interpretation of the nature of all living matter is intended as an alternative to medical mechanism, which dates back to the beginning of the 20th century. New ideas such as the notions of the human being as nestled in an evolutionary and ecological context, the spontaneous tendency of self-organizing systems for realization and concord, and the central role of consciousness in interpreting, planning, and expressing human reality are unavoidable today in attempts to scientifically understand all living matter, including human life.

  16. Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase

    DEFF Research Database (Denmark)

    Christensen, Caspar Elo; Kragelund, Birthe B; von Wettstein-Knowles, Penny

    2007-01-01

    Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual...... activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high...... degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic...

  17. PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer

    International Nuclear Information System (INIS)

    Owadally, Waheeda; Hurt, Chris; Timmins, Hayley; Parsons, Emma; Townsend, Sarah; Patterson, Joanne; Hutcheson, Katherine; Powell, Ned; Beasley, Matthew; Palaniappan, Nachi; Robinson, Max; Jones, Terence M.; Evans, Mererid

    2015-01-01

    Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes. The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint. PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity

  18. Species-related exposure of phase II metabolite gemfibrozil 1-O-β-glucuronide between human and mice: A net induction of mouse P450 activity was revealed.

    Science.gov (United States)

    Luo, Min; Dai, Manyun; Lin, Hante; Xie, Minzhu; Lin, Jiao; Liu, Aiming; Yang, Julin

    2017-12-01

    Gemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, six volunteers were recruited and took a therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0.75%) for 7 days, following which a cocktail-based inhibitory DDI experiment was performed. Plasma samples and liver tissues from mice were collected for determination of gemfibrozil, gem-glu concentration and cytochrome p450 enzyme (P450) induction analysis. In human, the molar ratio of gem-glu/gemfibrozil was 15% and 10% at the trough concentration and the concentration at 1.5 h after the 6th dose. In contrast, this molar ratio at steady state in mice was 91%, demonstrating a 6- to 9-fold difference compared with that in human. Interestingly, a net induction of P450 activity and in vivo inductive DDI potential in mice was revealed. The P450 activity was not inhibited although the gem-glu concentration was high. These data suggested species difference of relative gem-glu exposure between human and mice, as well as a net inductive DDI potential of gemfibrozil in mouse model. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity

    International Nuclear Information System (INIS)

    Nascimento, Martha do

    1996-01-01

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of β cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author)

  20. Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kirman, Christopher R., E-mail: ckirman@summittoxicology.com [Summit Toxicology, Orange Village, OH, 44022 (United States); Suh, Mina, E-mail: msuh@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States); Hays, Sean M., E-mail: shays@summittoxicology.com [Summit Toxicology, Allenspark, CO, 8040 (United States); Gürleyük, Hakan, E-mail: hakan@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); Gerads, Russ, E-mail: russ@brooksrand.com [Brooks Applied Labs, Bothell, WA, 98011 (United States); De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, 16132 Genoa (Italy); Parker, William, E-mail: william.parker@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Lin, Shu, E-mail: shu.lin@duke.edu [Duke University Medical Center, Department of Surgery, Durham, NC, 27710 (United States); Haws, Laurie C., E-mail: lhaws@toxstrategies.com [ToxStrategies, Inc., Katy, TX, 77494 (United States); Harris, Mark A., E-mail: mharris@toxstrategies.com [ToxStrategies, Inc., Austin, TX, 78751 (United States); Proctor, Deborah M., E-mail: dproctor@toxstrategies.com [ToxStrategies, Inc., Mission Viejo, CA, 92692 (United States)

    2016-09-01

    To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (< 0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. - Highlights: • SIDMS allows for measurement of Cr(VI) reduction rate in gastric fluid ex vivo • Human gastric fluid has three reducing pools • Cr(VI) in drinking water at < 0.7 mg/L is rapidly reduced in human gastric fluid • Reduction rate is concentration- and pH-dependent • A refined PK

  1. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  2. Near infrared spectroscopy combined with multivariate analysis for monitoring the ethanol precipitation process of fraction I + II + III supernatant in human albumin separation

    Science.gov (United States)

    Li, Can; Wang, Fei; Zang, Lixuan; Zang, Hengchang; Alcalà, Manel; Nie, Lei; Wang, Mingyu; Li, Lian

    2017-03-01

    Nowadays, as a powerful process analytical tool, near infrared spectroscopy (NIRS) has been widely applied in process monitoring. In present work, NIRS combined with multivariate analysis was used to monitor the ethanol precipitation process of fraction I + II + III (FI + II + III) supernatant in human albumin (HA) separation to achieve qualitative and quantitative monitoring at the same time and assure the product's quality. First, a qualitative model was established by using principal component analysis (PCA) with 6 of 8 normal batches samples, and evaluated by the remaining 2 normal batches and 3 abnormal batches. The results showed that the first principal component (PC1) score chart could be successfully used for fault detection and diagnosis. Then, two quantitative models were built with 6 of 8 normal batches to determine the content of the total protein (TP) and HA separately by using partial least squares regression (PLS-R) strategy, and the models were validated by 2 remaining normal batches. The determination coefficient of validation (Rp2), root mean square error of cross validation (RMSECV), root mean square error of prediction (RMSEP) and ratio of performance deviation (RPD) were 0.975, 0.501 g/L, 0.465 g/L and 5.57 for TP, and 0.969, 0.530 g/L, 0.341 g/L and 5.47 for HA, respectively. The results showed that the established models could give a rapid and accurate measurement of the content of TP and HA. The results of this study indicated that NIRS is an effective tool and could be successfully used for qualitative and quantitative monitoring the ethanol precipitation process of FI + II + III supernatant simultaneously. This research has significant reference value for assuring the quality and improving the recovery ratio of HA in industrialization scale by using NIRS.

  3. Near infrared spectroscopy combined with multivariate analysis for monitoring the ethanol precipitation process of fraction I+II+III supernatant in human albumin separation.

    Science.gov (United States)

    Li, Can; Wang, Fei; Zang, Lixuan; Zang, Hengchang; Alcalà, Manel; Nie, Lei; Wang, Mingyu; Li, Lian

    2017-03-15

    Nowadays, as a powerful process analytical tool, near infrared spectroscopy (NIRS) has been widely applied in process monitoring. In present work, NIRS combined with multivariate analysis was used to monitor the ethanol precipitation process of fraction I+II+III (FI+II+III) supernatant in human albumin (HA) separation to achieve qualitative and quantitative monitoring at the same time and assure the product's quality. First, a qualitative model was established by using principal component analysis (PCA) with 6 of 8 normal batches samples, and evaluated by the remaining 2 normal batches and 3 abnormal batches. The results showed that the first principal component (PC1) score chart could be successfully used for fault detection and diagnosis. Then, two quantitative models were built with 6 of 8 normal batches to determine the content of the total protein (TP) and HA separately by using partial least squares regression (PLS-R) strategy, and the models were validated by 2 remaining normal batches. The determination coefficient of validation (R p 2 ), root mean square error of cross validation (RMSECV), root mean square error of prediction (RMSEP) and ratio of performance deviation (RPD) were 0.975, 0.501g/L, 0.465g/L and 5.57 for TP, and 0.969, 0.530g/L, 0.341g/L and 5.47 for HA, respectively. The results showed that the established models could give a rapid and accurate measurement of the content of TP and HA. The results of this study indicated that NIRS is an effective tool and could be successfully used for qualitative and quantitative monitoring the ethanol precipitation process of FI+II+III supernatant simultaneously. This research has significant reference value for assuring the quality and improving the recovery ratio of HA in industrialization scale by using NIRS. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Human papillomaviruses associated with epidermodysplasia verruciformis. II. Molecular cloning and biochemical characterization of human papillomavirus 3a, 8, 10, and 12 genomes.

    OpenAIRE

    Kremsdorf, D; Jablonska, S; Favre, M; Orth, G

    1983-01-01

    The DNAs of four human papillomaviruses (HPVs) that were found in the benign lesions of three patients suffering from epidermodysplasia verruciformis have been characterized. The flat wart-like lesions and the macular lesions of patient 1 contained two viruses, HPV-3a and HPV-8, respectively, whose genomes had previously been only partially characterized. The flat wart-like lesions of patient 2 and the macular lesions of patient 3 each contained a virus previously considered as belonging to t...

  5. Culture of normal human blood cells in a diffusion chamber system II. Lymphocyte and plasma cell kinetics

    International Nuclear Information System (INIS)

    Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

    1979-01-01

    Normal human blood leukocytes were cultured in Millipore diffusion chambers implanted into the peritoneal cavities of irradiated mice. The evaluation of survival and proliferation kinetics of cells in lymphyocytic series suggested that the lymphoid cells are formed from transition of small and/or large lymphocytes, and the lymphoblasts from the lymphoid cells. There was also evidence indicating that some of the cells in these two compartments are formed by proliferation. The evaluation of plasmacytic series suggested that the plasma cells are formed from plasmacytoid-lymphocytes by transition, and the latter from the transition of lymphocytes. In addition, relatively a small fraction of cells in these two compartments are formed by proliferation. mature plasma cells do not and immature plasma cells do proliferate. Estimation of magnitude of plasma cells formed in the cultures at day 18 indicated that at least one plasma cell is formed for every 6 normal human blood lymphocytes introduced into the culture

  6. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

    Science.gov (United States)

    Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2014-01-01

    In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Heterologous expression, purification and characterization of human β-1,2-N-acetylglucosaminyltransferase II using a silkworm-based Bombyx mori nucleopolyhedrovirus bacmid expression system.

    Science.gov (United States)

    Miyazaki, Takatsugu; Kato, Tatsuya; Park, Enoch Y

    2018-02-03

    β-1,2-N-Acetylglucosaminyltransferase II (GnTII, EC 2.4.1.143) is a Golgi-localized type II transmembrane enzyme that catalyzes the transfer of N-acetylglucosamine to the 6-arm of the trimanosyl core of N-glycans, an essential step in the conversion of oligomannose-type to complex-type N-glycans. Despite its physiological importance, there have been only a few reports on the heterologous expression and structure-function relationship of this enzyme. Here, we constructed a silkworm-based Bombyx mori nucleopolyhedrovirus bacmid expression system and expressed human GnTII (hGnTII) lacking the N-terminal cytosolic tail and transmembrane region. The recombinant hGnTII was purified from silkworm larval hemolymph in two steps by using tandem affinity purification tags, with a yield of approximately 120 μg from 10 mL hemolymph, and exhibited glycosyltransferase activity and strict substrate specificity. The enzyme was found to be N-glycosylated by the enzymatic cleavage of glycans, while hGnTII expressed in insect cells had not been reported to be glycosylated. Although insects typically produce pauci-mannosidic-type glycans, the structure of N-glycans in the recombinant hGnTII was suggested to be of the complex type, and the removal of the glycans did not affect the enzymatic activity. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor.

    Science.gov (United States)

    Hombach, Andreas; Köhler, Heike; Rappl, Gunter; Abken, Hinrich

    2006-10-15

    Immune elimination of tumor cells requires the close cooperation between CD8+ CTL and CD4+ Th cells. We circumvent MHC class II-restriction of CD4+ T cells by expression of a recombinant immunoreceptor with an Ab-derived binding domain redirecting specificity. Human CD4+ T cells grafted with an immunoreceptor specific for carcinoembryonic Ag (CEA) are activated to proliferate and secrete cytokines upon binding to CEA+ target cells. Notably, redirected CD4+ T cells mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but mediated by perforin and granzyme because cytolysis is inhibited by blocking the release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha. CD4+ T cells redirected by Ab-derived immunoreceptors in a MHC class II-independent fashion substantially extend the power of an adoptive, Ag-triggered immunotherapy not only by CD4+ T cell help, but also by cytolytic effector functions. Because cytolysis is predominantly mediated via granzyme/perforin, target cells that are resistant to death receptor signaling become sensitive to a cytolytic attack by engineered CD4+ T cells.

  9. Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

    Directory of Open Access Journals (Sweden)

    Olfat Shaker

    2013-01-01

    Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

  10. Isolation of a cDNA for a Growth Factor of Vascular Endothelial Cells from Human Lung Cancer Cells: Its Identity with Insulin‐like Growth Factor II

    Science.gov (United States)

    Hagiwara, Koichi; Kobayashi, Tatsuo; Tobita, Masato; Kikyo, Nobuaki; Yazaki, Yoshio

    1995-01-01

    We have found growth‐promoting activity for vascular endothelial cells in the conditioned medium of a human lung cancer cell line, T3M‐11. Purification and characterization of the growth‐promoting activity have been carried out using ammonium sulfate precipitation and gel‐exclusion chromatography. The activity migrated as a single peak just after ribonuclease. It did not bind to a heparin affinity column. These results suggest that the activity is not a heparin‐binding growth factor (including fibroblast growth factors) or a vascular endothelial growth factor. To identify the molecule exhibiting the growth‐promoting activity, a cDNA encoding the growth factor was isolated through functional expression cloning in COS‐1 cells from a cDNA library prepared from T3M‐11 cells. The nucleotide sequence encoded by the cDNA proved to be identical with that of insulin‐like growth factor II. PMID:7730145

  11. Puzzle-based versus traditional lecture: comparing the effects of pedagogy on academic performance in an undergraduate human anatomy and physiology II lab.

    Science.gov (United States)

    Stetzik, Lucas; Deeter, Anthony; Parker, Jamie; Yukech, Christine

    2015-06-23

    A traditional lecture-based pedagogy conveys information and content while lacking sufficient development of critical thinking skills and problem solving. A puzzle-based pedagogy creates a broader contextual framework, and fosters critical thinking as well as logical reasoning skills that can then be used to improve a student's performance on content specific assessments. This paper describes a pedagogical comparison of traditional lecture-based teaching and puzzle-based teaching in a Human Anatomy and Physiology II Lab. Using a single subject/cross-over design half of the students from seven sections of the course were taught using one type of pedagogy for the first half of the semester, and then taught with a different pedagogy for the second half of the semester. The other half of the students were taught the same material but with the order of the pedagogies reversed. Students' performance on quizzes and exams specific to the course, and in-class assignments specific to this study were assessed for: learning outcomes (the ability to form the correct conclusion or recall specific information), and authentic academic performance as described by (Am J Educ 104:280-312, 1996). Our findings suggest a significant improvement in students' performance on standard course specific assessments using a puzzle-based pedagogy versus a traditional lecture-based teaching style. Quiz and test scores for students improved by 2.1 and 0.4% respectively in the puzzle-based pedagogy, versus the traditional lecture-based teaching. Additionally, the assessments of authentic academic performance may only effectively measure a broader conceptual understanding in a limited set of contexts, and not in the context of a Human Anatomy and Physiology II Lab. In conclusion, a puzzle-based pedagogy, when compared to traditional lecture-based teaching, can effectively enhance the performance of students on standard course specific assessments, even when the assessments only test a limited

  12. The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression.

    Science.gov (United States)

    Ho, Nelson; Morrison, Jodi; Silva, Andreza; Coomber, Brenda L

    2016-01-06

    Cancer cells heavily rely on the glycolytic pathway regardless of oxygen tension. Hexokinase II (HKII) catalyses the first irreversible step of glycolysis and is often overexpressed in cancer cells. 3-Bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of altering critical metabolic pathways in cancer cells. Abnormal vasculature within tumours leads to heterogeneous microenvironments, including glucose availability, which may affect drug sensitivity. The aim of the present study was to elucidate the mechanisms by which 3BP acts on colorectal cancer (CRC) cells with focus on the HKII/Akt signalling axis. High HKII-expressing cell lines were more sensitive to 3BP than low HKII-expressing cells. 3BP-induced rapid Akt phosphorylation at site Thr-308 and cell death via both apoptotic and necrotic mechanisms. Cells grown under lower glucose concentrations showed greater resistance towards 3BP. Cells with HKII knockdown showed no changes in 3BP sensitivity, suggesting the effects of 3BP are independent of HKII expression. These results emphasize the importance of the tumour microenvironment and glucose availability when considering therapeutic approaches involving metabolic modulation. © 2016 Authors.

  13. Lack of cross-resistance to fostriecin in a human small-cell lung carcinoma cell line showing topoisomerase II-related drug resistance

    NARCIS (Netherlands)

    de Jong, Steven; Zijlstra, J G; Mulder, Nanno; de Vries, Liesbeth

    1991-01-01

    Cells exhibiting decreased topoisomerase II (Topo II) activity are resistant to several drugs that require Topo II as an intermediate. These drugs are cytotoxic due to the formation of a cleavable complex between the drug, Topo II and DNA. Fostriecin belongs to a new class of drugs that inhibit Topo

  14. Soil physical degradation by human activities in the zone II of the basin of Burgos, Tamaulipas, Mexico; Degradacion fisica del suelo por actividades antorpicas en la zona II de la cuenca de burgos, Tamaulipas, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Arias Mino, F.; Espinosa Rmirez, M.; Andrade Limas, E.; Castro Meza, B.; Romero Diaz, A.

    2009-07-01

    The objective of this work was to characterize the physical degradation of the soil for antropic activities during the years 2007 and 2008 in the II zone of the Burgos Basin in Tamaulipas, Mexico. In this region, human action manifests itself due to activities such as agriculture, livestock and industry. The conventional farming, based mainly on the cultivation of sorghum, is characterized by great mechanization and tilling the soil which has contributed in large measure to aggravate erosion processes. There is also some logging, mainly for charcoal production and, recently, has joined the exploration and exploitation of natural gas. We used the methodology for Assessment of Soil Degradation (ASSOD) to identify, located and define the types of soil degradation within physiographic units. Results showed that nearly 74% of the study area presents some kind of degradation. The main process was water erosion, followed, by compaction and wind erosion. The main factors are essentially overgrazing and inadequate farming practices. Approximately 60% of the units evaluated presented a moderate level of degradation, but the speed of this process indicates that maintenance works are needed to reverse. (Author) 7 refs.

  15. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    DEFF Research Database (Denmark)

    Grey, Michael James; Ladouceur, Michel; Andersen, Jacob B.

    2001-01-01

    1. The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. 2. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h(-1) with the left ankle...... = 0.007), whereas the short latency component was unchanged (P = 0.653). 7. An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. 8. Our results support...

  16. DJ-1 Modulates Nuclear Erythroid 2-Related Factor-2-Mediated Protection in Human Primary Alveolar Type II Cells in Smokers.

    Science.gov (United States)

    Bahmed, Karim; Messier, Elise M; Zhou, Wenbo; Tuder, Rubin M; Freed, Curt R; Chu, Hong Wei; Kelsen, Steven G; Bowler, Russell P; Mason, Robert J; Kosmider, Beata

    2016-09-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.

  17. Copper (II)

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Valine (2 - amino - 3 – methylbutanoic acid), is a chemical compound containing .... Stability constant (Kf). Gibb's free energy. ) (. 1. −. ∆. Mol. JG. [CuL2(H2O)2] ... synthesis and characterization of Co(ii), Ni(ii), Cu (II), and Zn(ii) complexes with ...

  18. Human development II: We Need an Integrated Theory for Matter, Life and Consciousness to Understand Life and Healing

    Directory of Open Access Journals (Sweden)

    Sören Ventegodt

    2006-01-01

    Full Text Available For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient’s brain-mind and body-mind coming closer together due to the development of what we call “deep” cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call “holistic biology for holistic medicine”. We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination, brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor, and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain

  19. Human development II: we need an integrated theory for matter, life and consciousness to understand life and healing.

    Science.gov (United States)

    Ventegodt, Søren; Hermansen, Tyge Dahl; Nielsen, Maj Lyck; Clausen, Birgitte; Merrick, Joav

    2006-07-06

    For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient's brain-mind and body-mind coming closer together due to the development of what we call "deep" cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call "holistic biology for holistic medicine". We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination), brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor), and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain and consciousness, the

  20. Three-dimensional modelling of the human carotid artery using the lattice Boltzmann method: II. Shear analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, J [Cardiovascular Research Group, Physics, University of New England, Armidale, NSW 2351 (Australia); Buick, J M [Mechanical and Design Engineering, Anglesea Building, Anglesea Road, University of Portsmouth, Portsmouth, PO1 3DJ (United Kingdom)

    2008-10-21

    Near-wall shear is known to be important in the pathogenesis and progression of atherosclerosis. In this paper, the shear field in a three-dimensional model of the human carotid artery is presented. The simulations are performed using the lattice Boltzmann model and are presented at six times of interest during a physiologically accurate velocity waveform. The near-wall shear rate and von Mises effective shear are also examined. Regions of low near-wall shear rates are observed near the outer wall of the bifurcation and in the lower regions of the external carotid artery. These are regions where low near-wall velocity and circulatory flows have been observed and are regions that are typically prone to atherosclerosis.

  1. Three-dimensional modelling of the human carotid artery using the lattice Boltzmann method: II. Shear analysis

    International Nuclear Information System (INIS)

    Boyd, J; Buick, J M

    2008-01-01

    Near-wall shear is known to be important in the pathogenesis and progression of atherosclerosis. In this paper, the shear field in a three-dimensional model of the human carotid artery is presented. The simulations are performed using the lattice Boltzmann model and are presented at six times of interest during a physiologically accurate velocity waveform. The near-wall shear rate and von Mises effective shear are also examined. Regions of low near-wall shear rates are observed near the outer wall of the bifurcation and in the lower regions of the external carotid artery. These are regions where low near-wall velocity and circulatory flows have been observed and are regions that are typically prone to atherosclerosis.

  2. Functional brain mapping using H{sub 2}{sup 15}O positron emission tomography (II): mapping of human working memory

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Sung; Lee, Dong Soo; Lee, Sang Kun; Nam, Hyun Woo; Kim, Seok Ki; Park, Kwang Suk; Jeong, Jae Min; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    1998-08-01

    To localize and compare the neural basis of verbal and visual human working memory, we performed functional activation study using H{sub 2}{sup 15}O PET. Repeated H{sub 2}{sup 15}O PET scans with one control and three different activation tasks were performed on six right-handed normal volunteers. Each activation task was composed of 13 matching trials. On each trial, four targets, a fixation dot and a prove were presented sequentially and subject's tasks was to press a response button to indicate whether or not the prove was one of the previous targets. Short meaningful Korean words, simple drawings and monochromic pictures of human faces were used as matching objects for verbal or visual memory. All the images were spatially normalized and the differences between control and activation states were statistically analyzed using SPM96. Statistical analysis of verbal memory activation with short words showed activation in the left Broca's area, premotor cortex, cerebellum and right cingulate gyrus. In verbal memory with simple drawing, activation was shown in the larger regions including where activated with short words and left superior temporal cortex, basal ganglia, thalamus, prefrontal cortex, anterior portion of right superior temporal gyrus and right infero-lateral frontal cortex. On the other hand, the visual memory task activated predominantly right-sided structures, especially inferior frontal cortex, supplementary motor cortex and superior parietal cortex. The results are consistent with the hypothesis of the laterality and dissociation of the verbal and visual working memory from the invasive electrophysiological studies and emphasize the pivotal role of frontal cortex and cingulate gyrus in working memory system.

  3. Xenobiotic metabolism capacities of human skin in comparison with a 3D-epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: phase II enzymes.

    Science.gov (United States)

    Götz, Christine; Pfeiffer, Roland; Tigges, Julia; Ruwiedel, Karsten; Hübenthal, Ulrike; Merk, Hans F; Krutmann, Jean; Edwards, Robert J; Abel, Josef; Pease, Camilla; Goebel, Carsten; Hewitt, Nicola; Fritsche, Ellen

    2012-05-01

    The 7th Amendment to the EU Cosmetics Directive prohibits the use of animals in cosmetic testing for certain endpoints, such as genotoxicity. Therefore, skin in vitro models have to replace chemical testing in vivo. However, the metabolic competence neither of human skin nor of alternative in vitro models has so far been fully characterized, although skin is the first-pass organ for accidentally or purposely (cosmetics and pharmaceuticals) applied chemicals. Thus, there is an urgent need to understand the xenobiotic-metabolizing capacities of human skin and to compare these activities to models developed to replace animal testing. We have measured the activity of the phase II enzymes glutathione S-transferase, UDP-glucuronosyltransferase and N-acetyltransferase in ex vivo human skin, the 3D epidermal model EpiDerm 200 (EPI-200), immortalized keratinocyte-based cell lines (HaCaT and NCTC 2544) and primary normal human epidermal keratinocytes. We show that all three phase II enzymes are present and highly active in skin as compared to phase I. Human skin, therefore, represents a more detoxifying than activating organ. This work systematically compares the activities of three important phase II enzymes in four different in vitro models directly to human skin. We conclude from our studies that 3D epidermal models, like the EPI-200 employed here, are superior over monolayer cultures in mimicking human skin xenobiotic metabolism and thus better suited for dermatotoxicity testing. © 2012 John Wiley & Sons A/S.

  4. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhi, Xiuyi; Giroux-Leprieur, Etienne; Wislez, Marie; Hu, Mu; Zhang, Yi; Shi, Huaiyin; Du, Kaiqi; Wang, Lei

    2015-01-01

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.

  5. Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

    Science.gov (United States)

    Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

    2005-01-01

    We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

  6. NPRL-Z-1, as a new topoisomerase II poison, induces cell apoptosis and ROS generation in human renal carcinoma cells.

    Science.gov (United States)

    Wu, Szu-Ying; Pan, Shiow-Lin; Xiao, Zhi-Yan; Hsu, Jui-Ling; Chen, Mei-Chuan; Lee, Kuo-Hsiung; Teng, Che-Ming

    2014-01-01

    NPRL-Z-1 is a 4β-[(4"-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 2.38 µM via the MTT assay. We also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia-mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the activation of DNA damage signaling pathways, including Chk2, histone H2AX, and p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized the topoisomerase II (TOP2)-DNA complex, leading to TOP2cc formation. NPRL-Z-1-induced DNA damage signaling and apoptotic death was also reversed by TOP2α or TOP2β knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway and induced reactive oxygen species (ROS) generation. These results demonstrated that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z-1 may present a significant potential anticancer candidate against renal carcinoma.

  7. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R; Cassola, V F; Khoury, H J [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Prof. Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); De Melo Lima, V J [Department of Anatomy, Federal University of Pernambuco, Recife (Brazil); Robson Brown, K [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)], E-mail: rkramer@uol.com.br

    2010-01-07

    Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

  8. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

    Science.gov (United States)

    Kramer, R.; Cassola, V. F.; Khoury, H. J.; Vieira, J. W.; de Melo Lima, V. J.; Robson Brown, K.

    2010-01-01

    Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

  9. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    Science.gov (United States)

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  10. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    Science.gov (United States)

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  11. FY 1998 report on the result of the R and D of human sense measurement application technology. II. Main issue (1); 1998 nendo ningen kankaku keisoku oyo gijutsu no kenkyu kaihatsu itaku kenkyu seika hokokusho. 2. Honronhen (1)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    The paper reported the results of the FY 1998 R and D on human sense measurement application technology. Term I of this project is FY 1990-1994, when the interim evaluation was made. The project entered Term II of FY 1995-1998. In Term II, developments were made of the human sense measuring technology to make a 'measure' for health/safety and amenity/convenience which are important to human life, study of application examples for studying effectiveness by concretely applying this measuring technology to examples of products and working place/residential environment, evaluation simulation technology to qualitatively/objectively measure/evaluate amenity and adaptability in stead of humans, human sense database models which collected various human sense data obtained in measuring, etc. Through these technology development, the systematization of human sense indexes is attempted, and finally the following are conducted: development of measuring technology of kindness and evaluation equipment, environment/product design support, manual making for human sense measurement, construction of human sense database, etc. In FY 1998, the results of the measuring technology were mainly obtained. (NEDO)

  12. Contractile properties and sarcoplasmic reticulum calcium content in type I and type II skeletal muscle fibres in active aged humans.

    Science.gov (United States)

    Lamboley, C R; Wyckelsma, V L; Dutka, T L; McKenna, M J; Murphy, R M; Lamb, G D

    2015-06-01

    Muscle weakness in old age is due in large part to an overall loss of skeletal muscle tissue, but it remains uncertain how much also stems from alterations in the properties of the individual muscle fibres. This study examined the contractile properties and amount of stored intracellular calcium in single muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) adults. The maximum level of force production (per unit cross-sectional area) in fast twitch fibres in Old subjects was lower than in Young subjects, and the fibres were also less sensitive to activation by calcium. The amount of calcium stored inside muscle fibres and available to trigger contraction was also lower in both fast- and slow-twitch muscle fibres in the Old subjects. These findings indicate that muscle weakness in old age stems in part from an impaired capacity for force production in the individual muscle fibres. This study examined the contractile properties and sarcoplasmic reticulum (SR) Ca(2+) content in mechanically skinned vastus lateralis muscle fibres of Old (70 ± 4 years) and Young (22 ± 3 years) humans to investigate whether changes in muscle fibre properties contribute to muscle weakness in old age. In type II fibres of Old subjects, specific force was reduced by ∼17% and Ca(2+) sensitivity was also reduced (pCa50 decreased ∼0.05 pCa units) relative to that in Young. S-Glutathionylation of fast troponin I (TnIf ) markedly increased Ca(2+) sensitivity in type II fibres, but the increase was significantly smaller in Old versus Young (+0.136 and +0.164 pCa unit increases, respectively). Endogenous and maximal SR Ca(2+) content were significantly smaller in both type I and type II fibres in Old subjects. In fibres of Young, the SR could be nearly fully depleted of Ca(2+) by a combined caffeine and low Mg(2+) stimulus, whereas in fibres of Old the amount of non-releasable Ca(2+) was significantly increased (by > 12% of endogenous Ca(2+) content). Western

  13. Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

    Science.gov (United States)

    Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

    2008-05-01

    The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.

  14. Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon [College of Medicine, Univ. of Korea, Seoul (Korea, Republic of)

    2003-07-01

    Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology.

  15. Radioactive cDNA microarray (II): Gene expression profiling of antidepressant treatment by human cDNA microarray

    International Nuclear Information System (INIS)

    Lee, Ji Hye; Kang, Rhee Hun; Ham, Byung Joo; Lee, Min Su; Shin, Kyung Ho; Choe, Jae Gol; Kim, Meyoung Kon

    2003-01-01

    Major depressive disorder is a prevalent psychiatric disorder in primary care, associated with impaired patient functioning and well-being. Fluoxetine is a selective serotonin-reuptake inhibitors (SSRIs) and is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Objectives ; the aims of this study were two-fold: (1) to determine the usefulness for investigation of the transcription profiles in depression patients, and (2) to assess the differences in gene expression profiles between positive response group and negative response groups by fluoxetine treatment. This study included 53 patients with major depression (26 in positive response group with antidepressant treatment, 27 in negative response group with antidepressant treatment), and 53 healthy controls. To examine the difference of gene expression profile in depression patients, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 genes in total. Using 33p-labeled probes, this method provided highly sensitive gene expression profiles including brain receptors, drug metabolism, and cellular signaling. Gene transcription profiles were classified into several categories in accordance with the antidepressant gene-regulation. The gene profiles were significantly up-(22 genes) and down-(16 genes) regulated in the positive response group when compared to the control group. Also, in the negative response group, 35 genes were up-regulated and 8 genes were down-regulated when compared to the control group. Consequently, we demonstrated that radioactive human cDNA microarray is highly likely to be an efficient technology for evaluating the gene regulation of antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), by using high-throughput biotechnology

  16. Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors

    International Nuclear Information System (INIS)

    Randazzo, P.A.; Jarett, L.

    1990-01-01

    The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity

  17. Fold-recognition and comparative modeling of human α2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Balaji Petety V

    2006-04-01

    Full Text Available Abstract Background The 3-D structure of none of the eukaryotic sialyltransferases (SiaTs has been determined so far. Sequence alignment algorithms such as BLAST and PSI-BLAST could not detect a homolog of these enzymes from the protein databank. SiaTs, thus, belong to the hard/medium target category in the CASP experiments. The objective of the current work is to model the 3-D structures of human SiaTs which transfer the sialic acid in α2,3-linkage viz., ST3Gal I, II, III, IV, V, and VI, using fold-recognition and comparative modeling methods. The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%. Results Unlike the sequence similarity servers, fold-recognition servers identified CstII, a α2,3/8 dual-activity SiaT from Campylobacter jejuni as the homolog of all the six ST3Gals; the level of sequence similarity between CstII and ST3Gals is only 15–20% and the similarity is restricted to well-characterized motif regions of ST3Gals. Deriving template-target sequence alignments for the entire ST3Gal sequence was not straightforward: the fold-recognition servers could not find a template for the region preceding the L-motif and that between the L- and S-motifs. Multiple structural templates were identified to model these regions and template identification-modeling-evaluation had to be performed iteratively to choose the most appropriate templates. The modeled structures have acceptable stereochemical properties and are also able to provide qualitative rationalizations for some of the site-directed mutagenesis results reported in literature. Apart from the predicted models, an unexpected but valuable finding from this study is the sequential and structural relatedness of family GT42 and family GT29 SiaTs. Conclusion The modeled 3-D structures can be used for docking and other modeling studies and for the rational identification of residues to be mutated to impart desired properties such as altered stability, substrate

  18. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C

    1992-01-01

    is induced in the transformed heterogeneous rat islet cell clone, NHI-6F, by transient in vivo passage. During this process a transfected human insulin gene is coactivated with the endogenous nonallelic rat insulin I and II genes. Newly established cultures from NHI-6F insulinomas having a high frequency...

  19. Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal).

    Science.gov (United States)

    Spínola, H; Lemos, A; Couto, A R; Parreira, B; Soares, M; Dutra, I; Bruges-Armas, J; Brehm, A; Abreu, S

    2017-12-01

    This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.04) as protective. HLA-DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA-DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04-DQA1*03:01-DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1). © 2017 John Wiley & Sons Ltd.

  20. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  1. Type I and type II interferons upregulate functional type I interleukin-1 receptor in a human fibroblast cell line TIG-1.

    Science.gov (United States)

    Takii, T; Niki, N; Yang, D; Kimura, H; Ito, A; Hayashi, H; Onozaki, K

    1995-12-01

    The regulation of type I interleukin-1 receptor (IL-1R) expression by type I, interferon (IFN)-alpha A/D, and type II IFN, IFN-gamma, in a human fibroblast cell line TIG-1 was investigated. After 2 h stimulation with human IFN-alpha A/D or IFN-gamma, the levels of type I IL-1R mRNA increased. We previously reported that IL-1 upregulates transcription and cell surface molecules of type I IL-1R in TIG-1 cells through induction of prostaglandin (PG) E2 and cAMP accumulation. However, indomethacin was unable to inhibit the effect of IFNs, indicating that IFNs augment IL-1R expression through a pathway distinct from that of IL-1. The augmentation was also observed in other fibroblast cell lines. Nuclear run-on assays and studies of the stability of mRNA suggested that the increase in IL-1R mRNA was a result of the enhanced transcription of IL-1R gene. Binding studies using 125I-IL-1 alpha revealed that the number of cell surface IL-1R increased with no change in binding affinity by treatment with these IFNs. Pretreatment of the cells with IFNs enhanced IL-1-induced IL-6 production, indicating that IFNs upregulate functional IL-1R. IL-1 and IFNs are produced by the same cell types, as well as by the adjacent different cell types, and are concomitantly present in lesions of immune and inflammatory reactions. These results therefore suggest that IFNs exhibit synergistic effects with IL-1 through upregulation of IL-1R. Augmented production of IL-6 may also contribute to the reactions.

  2. Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

    Science.gov (United States)

    Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex. PMID:29361739

  3. The Antiproliferative Effect of Chakasaponins I and II, Floratheasaponin A, and Epigallocatechin 3-O-Gallate Isolated from Camellia sinensis on Human Digestive Tract Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Niichiro Kitagawa

    2016-11-01

    Full Text Available Acylated oleanane-type triterpene saponins, namely chakasaponins I (1 and II (2, floratheasaponin A (3, and their analogs, together with catechins—including (–-epigallocatechin 3-O-gallate (4, flavonoids, and caffeine—have been isolated as characteristic functional constituents from the extracts of “tea flower”, the flower buds of Camellia sinensis (Theaceae, which have common components with that of the leaf part. These isolates exhibited antiproliferative activities against human digestive tract carcinoma HSC-2, HSC-4, MKN-45, and Caco-2 cells. The antiproliferative activities of the saponins (1–3, IC50 = 4.4–14.1, 6.2–18.2, 4.5–17.3, and 19.3–40.6 µM, respectively were more potent than those of catechins, flavonoids, and caffeine. To characterize the mechanisms of action of principal saponin constituents 1–3, a flow cytometric analysis using annexin-V/7-aminoactinomycin D (7-AAD double staining in HSC-2 cells was performed. The percentage of apoptotic cells increased in a concentration-dependent manner. DNA fragmentation and caspase-3/7 activation were also detected after 48 h. These results suggested that antiproliferative activities of 1–3 induce apoptotic cell death via activation of caspase-3/7.

  4. A flow cytometry-based method for a high-throughput analysis of drug-stabilized topoisomerase II cleavage complexes in human cells.

    Science.gov (United States)

    de Campos-Nebel, Marcelo; Palmitelli, Micaela; González-Cid, Marcela

    2016-09-01

    Topoisomerase II (Top2) is an important target for anticancer therapy. A variety of drugs that poison Top2, including several epipodophyllotoxins, anthracyclines, and anthracenediones, are widely used in the clinic for both hematologic and solid tumors. The poisoning of Top2 involves the formation of a reaction intermediate Top2-DNA, termed Top2 cleavage complex (Top2cc), which is persistent in the presence of the drug and involves a 5' end of DNA covalently bound to a tyrosine from the enzyme through a phosphodiester group. Drug-induced Top2cc leads to Top2 linked-DNA breaks which are the major responsible for their cytotoxicity. While biochemical detection is very laborious, quantification of drug-induced Top2cc by immunofluorescence-based microscopy techniques is time consuming and requires extensive image segmentation for the analysis of a small population of cells. Here, we developed a flow cytometry-based method for the analysis of drug-induced Top2cc. This method allows a rapid analysis of a high number of cells in their cell cycle phase context. Moreover, it can be applied to almost any human cell type, including clinical samples. The methodology is useful for a high-throughput analysis of drugs that poison Top2, allowing not just the discrimination of the Top2 isoform that is targeted but also to track its removal. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

  5. Metabolism of apolipoproteins A-I and A-II in human high-density lipoprotein: a mathematical approach for analysis of their specific activity decay curves

    International Nuclear Information System (INIS)

    Atmeh, R.F.

    1987-01-01

    The differential rate equations describing the compartmental model of human high-density lipoprotein (HDL) were integrated by means of Laplace transforms and an exponential equation was obtained for each of the three compartments. These equations were used to fit the observed plasma decay data and give estimates for the rate constants of the system by means of a written computer program. Furthermore, these estimates were used to calculate the exponential constants of the integrated equations. Consequently, the amount of label in any of the intravascular, extravascular, and urine compartments can be calculated as a fraction of the original dose of label at any time point. This method was tested using data for the (AI)HDL subclass because it contains only apolipoprotein A-I as the major apolipoprotein and does not contain apolipoprotein A-II. The calculated plasma and urine radioactivity data were compared with the experimentally obtained data from two normolipoproteinemic subjects and found to be in good agreement. The significance of this method is its application to the analysis of the decay data of the individual apolipoproteins of (AI + AII) HDL subclass where the urinary radioactivity data resulting from the individual apolipoprotein breakdown on the native particle cannot be measured experimentally at present. Such data are essential for the detailed calculation of the kinetic parameters of these apolipoproteins

  6. Intracellular distribution and mechanisms of actions of photosensitizer Zinc(II)-phthalocyanine solubilized in Cremophor EL against human hepatocellular carcinoma HepG2 cells.

    Science.gov (United States)

    Shao, Jingwei; Dai, Yongchao; Zhao, Wenna; Xie, Jingjing; Xue, Jinping; Ye, Jianhui; Jia, Lee

    2013-03-01

    Zinc(II)-phthalocyanine (ZnPc) is a metal photosensitizer. In the present study, we formulated the poorly-soluble ZnPc in Cremophor EL solution to enhance its solubility and determined its intracellular distribution and mechanisms of action on human hepatocellular carcinoma HepG2 cells. ZnPc uptake by the cells reached a plateau by 8h. ZnPc primarily located in mitochondria, lysosome and endoplasmic reticulum. The concentration-growth inhibition curves of ZnPc on the cell lines were pharmacodynamically enhanced by 10-50 folds by irradiation. Once irradiated, ZnPc produced significant amount of reactive oxygen species (ROS), activated caspase-3 and caspase-9, arrested cell cycle mainly at G2/M stage, and decreased membrane potential (ΔΨm) of HepG2 cells. In conclusion, the present study first elucidated cellular and molecular mechanisms of ZnPc on HepG2 cells. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

    Science.gov (United States)

    Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

    2014-12-01

    Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

  8. Intermediate conformation between native β-sheet and non-native α-helix is a precursor of trifluoroethanol-induced aggregation of Human Carbonic Anhydrase-II

    International Nuclear Information System (INIS)

    Gupta, Preeti; Deep, Shashank

    2014-01-01

    Highlights: • HCAII forms amyloid-like aggregates at moderate concentration of trifluoroethanol. • Protein adopts a state between β-sheet and α-helix at moderate % of TFE. • Hydrophobic surface(s) of partially structured conformation forms amyloid. • High % of TFE induces stable α-helical state preventing aggregation. - Abstract: In the present work, we examined the correlation between 2,2,2-trifluoroethanol (TFE)-induced conformational transitions of human carbonic anhydrase II (HCAII) and its aggregation propensity. Circular dichroism data indicates that protein undergoes a transition from β-sheet to α-helix on addition of TFE. The protein was found to aggregate maximally at moderate concentration of TFE at which it exists somewhere between β-sheet and α-helix, probably in extended non-native β-sheet conformation. Thioflavin-T (ThT) and Congo-Red (CR) assays along with fluorescence microscopy and transmission electron microscopy (TEM) data suggest that the protein aggregates induced by TFE possess amyloid-like features. Anilino-8-naphthalene sulfonate (ANS) binding studies reveal that the exposure of hydrophobic surface(s) was maximum in intermediate conformation. Our study suggests that the exposed hydrophobic surface and/or the disruption of the structural features protecting a β-sheet protein might be the major reason(s) for the high aggregation propensity of non-native intermediate conformation of HCAII

  9. Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.

    Science.gov (United States)

    van der Bel, René; Coolen, Bram F; Nederveen, Aart J; Potters, Wouter V; Verberne, Hein J; Vogt, Liffert; Stroes, Erik S G; Krediet, C T Paul

    2016-03-28

    The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, PMRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  10. The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema.

    Science.gov (United States)

    Tan, Li Hui; Bahmed, Karim; Lin, Chih-Ru; Marchetti, Nathaniel; Bolla, Sudhir; Criner, Gerard J; Kelsen, Steven; Madesh, Muniswamy; Kosmider, Beata

    2018-02-23

    Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.

  11. CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

    Directory of Open Access Journals (Sweden)

    Ming-Horng Tsai

    2017-08-01

    Full Text Available Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9 induced migration of human aortic smooth muscle cells (HASMCs is the most common and basic pathological feature. Carbon monoxide (CO, a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2 on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47phox, Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed. Keywords: Angiotensin II, Carbon monoxide, Human aortic smooth muscle cell, Inflammation, Matrix metallopeptidase

  12. Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

    Directory of Open Access Journals (Sweden)

    Aftab A. Ansari

    2003-01-01

    Full Text Available In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1 to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR β1*0301 pulsed with the influenza A matrix 1 (58-66 peptide (M1 were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC. Pretreatment of these M1-VAC targets with IFN-γ partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-γ pretreated W-1's could not process tetanus toxin (TT or present the TT(830-843 peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-γ to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-γ pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.

  13. Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

    Science.gov (United States)

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-02-10

    The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients with metastatic human epidermal growth factor receptor 2-positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m(2) once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. © 2014 by American Society of Clinical Oncology.

  14. Angiotensin II receptor one (AT1) mediates dextrose induced endoplasmic reticulum stress and superoxide production in human coronary artery endothelial cells.

    Science.gov (United States)

    Haas, Michael J; Onstead-Haas, Luisa; Lee, Tracey; Torfah, Maisoon; Mooradian, Arshag D

    2016-10-01

    Renin-angiotensin-aldosterone system (RAAS) has been implicated in diabetes-related vascular complications partly through oxidative stress. To determine the role of angiotensin II receptor subtype one (AT1) in dextrose induced endoplasmic reticulum (ER) stress, another cellular stress implicated in vascular disease. Human coronary artery endothelial cells with or without AT1 receptor knock down were treated with 27.5mM dextrose for 24h in the presence of various pharmacologic blockers of RAAS and ER stress and superoxide (SO) production were measured. Transfection of cells with AT1 antisense RNA knocked down cellular AT1 by approximately 80%. The ER stress was measured using the placental alkaline phosphatase (ES-TRAP) assay and western blot analysis of glucose regulated protein 78 (GRP78), c-jun-N-terminal kinase 1 (JNK1), phospho-JNK1, eukaryotic translation initiation factor 2α (eIF2α) and phospho-eIF2α measurements. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. In cells with AT1 knock down, dextrose induced ER stress was significantly blunted and treatment with 27.5mM dextrose resulted in significantly smaller increase in SO production compared to 27.5mM dextrose treated and sham transfected cells. Dextrose induced ER stress was reduced with pharmacologic blockers of AT1 (losartan and candesartan) and mineralocorticoid receptor blocker (spironolactone) but not with angiotensin converting enzyme inhibitors (captopril and lisinopril). The dextrose induced SO generation was inhibited by all pharmacologic blockers of RAAS tested. The results indicate that dextrose induced ER stress and SO production in endothelial cells are mediated at least partly through AT1 receptor activation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

    Science.gov (United States)

    Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

    2015-01-01

    Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

  16. Structural and catalytic characterization of a thermally stable and acid-stable variant of human carbonic anhydrase II containing an engineered disulfide bond

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D.; Habibzadegan, Andrew [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); Tu, Chingkuang; Silverman, David N. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States)

    2013-08-01

    The X-ray crystallographic structure of the disulfide-containing HCAII (dsHCAII) has been solved to 1.77 Å resolution and revealed that successful oxidation of the cysteine bond was achieved while also retaining desirable active-site geometry. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration of CO{sub 2} to bicarbonate and a proton. Recently, there has been industrial interest in utilizing CAs as biocatalysts for carbon sequestration and biofuel production. The conditions used in these processes, however, result in high temperatures and acidic pH. This unfavorable environment results in rapid destabilization and loss of catalytic activity in CAs, ultimately resulting in cost-inefficient high-maintenance operation of the system. In order to negate these detrimental industrial conditions, cysteines at residues 23 (Ala23Cys) and 203 (Leu203Cys) were engineered into a wild-type variant of human CA II (HCAII) containing the mutation Cys206Ser. The X-ray crystallographic structure of the disulfide-containing HCAII (dsHCAII) was solved to 1.77 Å resolution and revealed that successful oxidation of the cysteine bond was achieved while also retaining desirable active-site geometry. Kinetic studies utilizing the measurement of {sup 18}O-labeled CO{sub 2} by mass spectrometry revealed that dsHCAII retained high catalytic efficiency, and differential scanning calorimetry showed acid stability and thermal stability that was enhanced by up to 14 K compared with native HCAII. Together, these studies have shown that dsHCAII has properties that could be used in an industrial setting to help to lower costs and improve the overall reaction efficiency.

  17. The human RNA polymerase II-associated factor 1 (hPaf1: a new regulator of cell-cycle progression.

    Directory of Open Access Journals (Sweden)

    Nicolas Moniaux

    2009-09-01

    Full Text Available The human PAF (hPAF complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle.Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation.Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development.

  18. A clinical stydy on the effectiveness of slow - resorbing collagen membrane barrier therapy to guide regeneration in mandibular class II furcations in human

    Directory of Open Access Journals (Sweden)

    Abolfazli N

    1998-09-01

    Full Text Available The present clinical trial was designed to evaluate the regenerative potential of periodontal tissues in degree II"nfurcation defects at mandibular molars of human using a slow-resorbing collagen membrane and a surgical treatment"ntechnique based on the principles of guided tissue regeneration."nThe patient sampleinclude 8 subjects who had periodontal lessions in right and left mandibular molars regions, including moderate to advance periodonal destruction within the radicular area. Following a baseline examination including recording the clinical measurements (PD, Al, HC, F.G.M , the furcation- involved molars were randomly assigned in each patient to either a test or a control treatment procedure. Included the evevation of mucoperiosteal flaps, recording measurement from the cemento enamel junction (C.E.J directly coronal to the furcation area to the alveolar crest and to the base of the defect-Horizontal furcation measurements were also made using a William's probe, finally a collagen membrrane placed on the involved area to cover the entrance of the furcation and adjucent root surfaces as well as a portion of the alveolar bone apical to the crest. The flaps were repositioned and secured with interdental sutures. A procedure identical to the one used at the test teeth was Performed at the control teeth region with the exception of the placement of the collagen membrance. Following surgery all patients were placed on a plaque control regimen. All Patients received normal postsurgical care and at 6 month post-surgery were scheduled for re-entry surgery. Before re-entry surgery all clinical parameters recorded again. The re-entry mucoperiosteal flaps were designed to expose the furcation area for measurements, as describedabove. There was clinical improvement in all measurements made in both the test and control patients (especially in test group over the 6 month period. The horizontal and vertical furcation measurements did yield a

  19. NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ

    DEFF Research Database (Denmark)

    Karosiene, Edita; Rasmussen, Michael; Blicher, Thomas

    2013-01-01

    Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importa......MHCIIpan-3.0 method is the first pan-specific predictor covering all HLA class II molecules with known sequences including HLA-DR, HLA-DP, and HLA-DQ. The NetMHCpan-3.0 method is available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.0....

  20. Photophysical characterisation and studies of the effect of palladium(II) 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin on isometric contraction of isolated human mesenteric artery: Good news for photodynamic therapy

    Czech Academy of Sciences Publication Activity Database

    Dimitrova, D. Z.; Kubát, Pavel; Dimitrov, S.; Belokonski, E.; Bogoeva, V.

    2014-01-01

    Roč. 11, č. 3 (2014), s. 391-399 ISSN 1572-1000 R&D Projects: GA ČR(CZ) GA13-12496S Institutional support: RVO:61388955 Keywords : Palladium(II) 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin * Human mesenteric artery * Isometric contraction Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.014, year: 2014

  1. The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation.

    Science.gov (United States)

    Xiao, Yucheng; Blumenthal, Kenneth; Jackson, James O; Liang, Songping; Cummins, Theodore R

    2010-12-01

    The voltage-gated sodium channel Na(v)1.7 plays a crucial role in pain, and drugs that inhibit hNa(v)1.7 may have tremendous therapeutic potential. ProTx-II and huwentoxin-IV (HWTX-IV), cystine knot peptides from tarantula venoms, preferentially block hNa(v)1.7. Understanding the interactions of these toxins with sodium channels could aid the development of novel pain therapeutics. Whereas both ProTx-II and HWTX-IV have been proposed to preferentially block hNa(v)1.7 activation by trapping the domain II voltage-sensor in the resting configuration, we show that specific residues in the voltage-sensor paddle of domain II play substantially different roles in determining the affinities of these toxins to hNa(v)1.7. The mutation E818C increases ProTx-II's and HWTX-IV's IC(50) for block of hNa(v)1.7 currents by 4- and 400-fold, respectively. In contrast, the mutation F813G decreases ProTx-II affinity by 9-fold but has no effect on HWTX-IV affinity. It is noteworthy that we also show that ProTx-II, but not HWTX-IV, preferentially interacts with hNa(v)1.7 to impede fast inactivation by trapping the domain IV voltage-sensor in the resting configuration. Mutations E1589Q and T1590K in domain IV each decreased ProTx-II's IC(50) for impairment of fast inactivation by ~6-fold. In contrast mutations D1586A and F1592A in domain-IV increased ProTx-II's IC(50) for impairment of fast inactivation by ~4-fold. Our results show that whereas ProTx-II and HWTX-IV binding determinants on domain-II may overlap, domain II plays a much more crucial role for HWTX-IV, and contrary to what has been proposed to be a guiding principle of sodium channel pharmacology, molecules do not have to exclusively target the domain IV voltage-sensor to influence sodium channel inactivation.

  2. In vitro effects of estrogen and progesterone containing drugs on human erythrocyte carbonic anhydrase I and II isozymes in women smokers and nonsmokers

    Directory of Open Access Journals (Sweden)

    Mine Islimye Taskin

    2015-09-01

    Conclusion: The results of the current study provide important information to clinicians about how to consider the possible adverse effects of these drugs which are produced as a result of inhibition of CA I and CA II enzyme. Clinicians should take into consideration the side effects caused by CA I and CA II enzyme inhibition when prescribing these drugs in the treatment of different clinical conditions, especially in women who smoke.

  3. Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

    Science.gov (United States)

    Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

    2017-05-01

    Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of

  4. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    International Nuclear Information System (INIS)

    Cantú de León, David; Yu, Neng; Yunis, Edmond J; Granados, Julio; Pérez-Montiel, Delia; Villavicencio, Verónica; Carranca, Alejandro García; Betancourt, Alejandro Mohar; Acuña-Alonzo, Victor; López-Tello, Alberto; Vargas-Alarcón, Gilberto; Barquera, Rodrigo

    2009-01-01

    The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

  5. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

    Science.gov (United States)

    Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

    2016-03-20

    Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

  6. TO BE IS NOT-TO-BE: NIHILISM, IDEOLOGY AND THE QUESTION OF BEING IN HEIDEGGER’S POLITICAL PHILOSOPHY PART II: TRUTH, HUMANISM AND TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Mihai NOVAC

    2016-06-01

    Full Text Available Allegedly, Heidegger never quite finished Being and Time: his initial intention had consisted in the determination of the meaning of Being as such, apart from Dasein’s own existentiality. Afterwards, however, and despite the growing public excitement revolving around the published unfinished version of his project, his preoccupations, thematic conceptuality and very language, apparently started to shift away towards a strange and unfamiliar stance which he would never leave. Quite surely, his Nazi flirtation and subsequent withdrawal did not help in bringing clarity over this. On the other hand, this was not necessarily unexpected (although not necessarily to be expected, as well. What I mean to say is that for someone reading Being and time in spirit and not in law, the possibility of such a substantive rethought of his initial scheme is present throughout the work. One’s changing one’s mind with respect to oneself is, after all, one of the basic possibilities conveyed by Dasein’s achieved resoluteness [Entschlossenheit]. Furthermore, despite his apparent reorientation, I think we can speak of some sort of attitudinal unity between Heidegger’s initial and later work, conceptually mediated by the relationship between Dasein’s Being-unto-death [Sein-zum-Tode] and the so called concealedness [Verborgenheit] of Being.. That is precisely what I aim to lay bare through this conceptual reconstruction of some of his later works: (i On the Essence of Truth (1930 and (ii Letter on Humanism (1946. Basically, I will try to show that if in Being and Time he tried to come to Being from Dasein, in his later work he tries to get to Da-sein from Being, fact which unsurprisingly brought along some reconsiderations but that, broadly speaking, essentially amounts to what he set out to do in his initial ontological project. Surprisingly, the most concrete instance of this pendulation between Dasein and Being is to be found, at least to my knowledge, in

  7. Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.

    Science.gov (United States)

    Mishra, Ritu; Benlhabib, Houda; Guo, Wei; Lerma Cervantes, Connie B; Mendelson, Carole R

    2018-06-01

    The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMP-induced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. Copyright © 2018 American Society for Microbiology.

  8. Biosorption of Fe (II) and Cd (II) ions from aqueous solution using a ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Biosorption of Fe (II) and Cd (II) ions from aqueous solution using a low cost ... human activities in the environment poses a lot of risk ... ion exchange or reverse osmosis, electrochemical treatment ..... is the adsorption coefficient, n indicates the.

  9. Immunoassays for the measurement of IGF-II, IGFBP-2 and -3, and ICTP as indirect biomarkers of recombinant human growth hormone misuse in sport. Values in selected population of athletes.

    Science.gov (United States)

    Abellan, Rosario; Ventura, Rosa; Palmi, Ilaria; di Carlo, Simonetta; Bacosi, Antonella; Bellver, Montse; Olive, Ramon; Pascual, Jose Antonio; Pacifici, Roberta; Segura, Jordi; Zuccaro, Piergiorgio; Pichini, Simona

    2008-11-04

    Insulin-like growth factor-II (IGF-II), insulin-like growth factor binding proteins (IGFBPs) -2 and -3 and C-terminal telopeptide of type I collagen (ICTP) have been proposed, among others, as indirect biomarkers of the recombinant human growth hormone misuse in sport. An extended intra- and inter-laboratory validation of commercially available immunoassays for biomarkers detection was performed. ELISA assays for total IGF-II, IGFBP-2 and IGFBP-3 (IGF-II/ELISA1: DSLabs, IGFBP-2/ELISA2: Biosource, and IGFBP-3/ELISA3: BioSource) and an EIA assay for ICTP (ICTP/EIA: Orion Diagnostica) were evaluated. The inter- and intra-laboratory precision values were acceptable for all evaluated assays (maximum imprecision of 30% and 66% were found only for the lowest quality control samples of IGF-II and IGFBP-3). Correct accuracy was obtained for all inter-laboratory immunoassays and for IGFBP-2 intra-laboratory immunoassay. The range of concentrations found in serum samples under investigation was always covered by the calibration curves of the studied immunoassays. However, 11% and 15% of the samples felt below the estimated LOQ for IGF-II and ICTP, respectively, in the zone where lower precision was obtained. Although the majority of evaluated assays showed an overall reliability not always suitable for antidoping control analysis, relatively high concordances between laboratory results were obtained for all assays. Evaluated immunoassays were used to measure serum concentrations of IGF-II, IGFBP-2 and -3 and ICTP in elite athletes of various sport disciplines at different moments of the training season; in recreational athletes at baseline conditions and finally in sedentary individuals. Serum IGF-II was statistically higher both in recreational and elite athletes compared to sedentary individuals. Elite athletes showed lower IGFBP-2 and higher IGFBP-3 concentration with respect to recreational athletes and sedentary people. Among elite athletes, serum IGFBP-3 (synchronized

  10. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  11. MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study.

    Science.gov (United States)

    Albarran Y Carvajal, Antonio; de la Garza, Alfonso; Cruz Quiroz, Benitez Jose Cecilio; Vazquez Zea, Eduardo; Díaz Estrada, Ismael; Mendez Fuentez, Ernesto; López Contreras, Mario; Andrade-Manzano, Alejandro; Padilla, Santiago; Varela, Axel Ramírez; Rosales, Ricardo

    2007-01-01

    Human papillomavirus (HPV) is the etiologic agent for warts and cervical cancer. In Mexico, the death rate from cervical cancer is extremely high, and statistical data show that since 1990 the number of deaths is increasing. Condylomas and cancer of the penis are the most common lesions presented in men; bladder and prostate cancer in men are also associated with the presence of HPV. Since HPV is transmitted by sexual intercourse, treating both partners is necessary in order to eliminate the virus in the population. Approaches to this include preventative vaccines such as Gardasil, and therapeutic vaccines to treat established infections in both men and women. This will be the only way to decrease the numbers of deaths due to this malignancy. We conducted a phase I/II clinical trial to evaluate the potential use of the recombinant vaccinia viral vaccine MVA E2 (composed of modified vaccinia virus Ankara [MVA] expressing the E2 gene of bovine papillomavirus) to treat flat condyloma lesions associated with oncogenic HPV in men. Fifty male patients with flat condyloma lesions were treated with either MVA E2 therapeutic vaccine or fluorouracil (5-fluorouracil). Thirty men received the therapeutic vaccine, at a total of 10(6) virus particles per dose, administered directly into the urethra once every week over a 4-week period. Twenty control patients were treated with 5% fluorouracil 1mL twice weekly over a 4-week period directly into the urethra. Reduction of lesions or absence of papillomavirus infection was monitored by colposcopy and histologic analysis. The immune response after MVA E2 treatment was determined by measuring the antibodies against the MVA E2 virus and by analyzing the lymphocyte cytotoxic activity against cancer cells bearing oncogenic papillomavirus. Presence of papillomavirus was determined by the Hybrid Capture method. Twenty-eight of 30 patients showed no lesion or presence of papillomavirus as diagnosed by colposcopy and brush histologic

  12. Growth-dependent modulation of casein kinase II and its substrate nucleolin in primary human cell cultures and HeLa cells

    DEFF Research Database (Denmark)

    Schneider, H R; Issinger, O G

    1989-01-01

    We have previously provided evidence that casein kinase II (CKII) and its substrate nucleolin increase concomitantly during certain development stages during embryogenesis (Schneider et al., Eur. J. Biochem. 161, 733-738). We now show that during normal growth of primary cell cultures and He...

  13. Human-like behavior of robot arms: general considerations and the handwriting task-part II: The robot arm in handwriting

    NARCIS (Netherlands)

    Potkonjak, V.; Kostic, D.; Tzafestas, S.; Popovic, M.; Lazarevic, M.; Djordjevic, G.

    2001-01-01

    This paper (Part II) investigates the motion of a redundant anthropomorphic arm during the writing task. Two approaches are applied. The first is based on the concept of distributed positioning which is suitable to model the "writing" task before the occurrence of fatigue symptoms. The second

  14. TBscore II

    DEFF Research Database (Denmark)

    Rudolf, Frauke; Lemvik, Grethe; Abate, Ebba

    2013-01-01

    Abstract Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing...... them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start...

  15. Pb II

    African Journals Online (AJOL)

    Windows User

    This investigation describes the use of non-living biomass of Aspergillus caespitosus for removal of ... Pb(II) production has exceeded 3.5 million tons per year. It has been used in the ... This biomass was selected after screening a wide range of microbes. .... prolonged, which proved better biopolymer in metal uptake (Gadd ...

  16. Optimization of automation: II. Estimation method of ostracism rate based on the loss of situation awareness of human operators in nuclear power plants

    International Nuclear Information System (INIS)

    Lee, Seung Min; Kim, Man Cheol; Kim, Jong Hyun; Seong, Poong Hyun

    2015-01-01

    Highlights: • We analyze the relationship between Out-of-the-Loop and the loss of human operators’ situation awareness. • We propose an ostracism rate estimation method by only considering the negative effects of automation. • The ostracism rate reflects how much automation interrupts human operators to receive information. • The higher the ostracism rate is, the lower the accuracy of human operators’ SA will be. - Abstract: With the introduction of automation in various industries including the nuclear field, its side effect, referred to as the Out-of-the-Loop (OOTL) problem, has emerged as a critical issue that needs to be addressed. Many studies have been attempted to analyze and solve the OOTL problem, but this issue still needs a clear solution to provide criteria for introducing automation. Therefore, a quantitative estimation method for identifying negative effects of automation is proposed in this paper. The representative aspect of the OOTL problem in nuclear power plants (NPPs) is that human operators in automated operations are given less information than human operators in manual operations. In other words, human operators have less opportunity to obtain needed information as automation is introduced. From this point of view, the degree of difficulty in obtaining information from automated systems is defined as the Level of Ostracism (LOO). Using the LOO and information theory, we propose the ostracism rate, which is a new estimation method that expresses how much automation interrupts human operators’ situation awareness. We applied production rules to describe the human operators’ thinking processes, Bayesian inference to describe the production rules mathematically, and information theory to calculate the amount of information that human operators receive through observations. The validity of the suggested method was proven by conducting an experiment. The results show that the ostracism rate was significantly related to the accuracy

  17. Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. II. Neurobehavioral effects of white spirit in rat and human

    NARCIS (Netherlands)

    Lammers, J.H.C.M.; Emmen, H.H.; Muijser, H.; Hoogendijk, E.M.G.; McKee, R.H.; Owen, D.E.; Kulig, B.M.

    2007-01-01

    To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate

  18. Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis

    OpenAIRE

    Ebrahim, Karim; Shirazi, Farshad H.; Vatanpour, Hosein; zare, Abas; Kobarfard, Farzad; Rabiei, Hadi

    2014-01-01

    Purpose Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against...

  19. Study of the interaction between two newly synthesized cyclometallated platinum (II) complexes and human serum albumin: Spectroscopic characterization and docking simulation

    Energy Technology Data Exchange (ETDEWEB)

    Yousefi, Reza, E-mail: ryousefi@shirazu.ac.ir [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Mohammadi, Roghayeh [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Taheri-Kafrani, Asghar [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Bagher Shahsavani, Mohammad [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Dadkhah Aseman, Marzieh; Masoud Nabavizadeh, S.; Rashidi, Mehdi [Department of Chemistry, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Poursasan, Najmeh; Moosavi-Movahedi, Ali-Akbar [Institute of Biochemistry and Biophysics (IBB), the University of Tehran, Tehran (Iran, Islamic Republic of)

    2015-03-15

    This study describes HSA binding properties of two cyclometalated platinum (II) complexes with non-leaving lipophilic ligands; deprotonated 2-phenylpyridine (ppy): C{sub 1} and deprotonated benzo [h]quinolone (bhq): C{sub 2}, using UV–vis, fluorescence and circular dichroism (CD) spectroscopy. The absorption spectra of HSA decreased in the presence of increasing concentration of these complexes, reflecting HSA structural alteration after drug's binding. Also the thermodynamic parameters (ΔG, ΔH and ΔS) that obtained from Trp fluorescence study revealed that the interaction between these complexes and HSA were spontaneous. In addition, C{sub 1} with flexible chemical structure indicated significantly higher fluorescence quenching and binding affinity to HSA than C{sub 2} which possesses a higher structural rigidity. The ANS fluorescence results also indicated that two Pt (II) complexes were competing for binding to the hydrophobic regions of HSA. Moreover, CD results demonstrated that C{sub 2} complex induced alteration of HSA conformation to more significant extent compared to C{sub 1}. The molecular docking results revealed the involvement of π–π stacking and hydrophobic interaction between these complexes and the protein. Overall, this study may highlight the significance of structural flexibility in designing of future anticancer Pt (II) complexes with improved binding affinity for HSA. - Highlights: • HSA is a general transport carrier for a wide variety of ligands such as metabolites and pharmaceutical drugs. • The HSA binding properties of two structurally related cyclometallated platinum (II) complexes (C{sub 1} and C{sub 2}) were studied. • The complexes can bind to HSA and induce structural alteration in this protein. • The thermodynamic parameters revealed that the interactions were spontaneous and mainly hydrophobic driven. • C{sub 1} with flexible chemical structure indicated a higher binding affinity for HSA than C{sub 2}.

  20. Selective flotation-spectrophotometric determination of trace copper(II) in natural waters, human blood and drug samples using phenanthraquinone monophenylthiosemicarbazone.

    Science.gov (United States)

    Khalifa, M E; Akl, M A; Ghazy, S E

    2001-06-01

    Copper(II) forms 1:1 and 1:2 intense red complexes with phenanthraquinone monophenylthiosemicarbazone (PPT) at pH 3-3.5 and > or =6.5, respectively. These complexes exhibit maximal absorbance at 545 and 517 nm, the molar absorptivity being 2.3 x 10(4) and 4.8 x 10(4) l mol(-1) cm(-1), respectively. However, the 1:1 complex was quantitatively floated with oleic acid (HOL) surfactant in the pH range 4.5-5.5, providing a highly selective and sensitive procedure for the spectrophotometric determination of CuII. The molar absorptivity of the floated Cu-PPT complex was 1.5 x 10(5) l mol)(-1) cm(-1). Beer's law was obeyed over the range 3-400 ppb at 545 nm. The analytical parameters affecting the flotation process and hence the determination of copper traces were reported. Also, the structure of the isolated solid complex and the mechanism of flotation were suggested. Moreover, the procedure was successfully applied to the analysis of CuII in natural waters, serum blood and some drug samples.

  1. Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth

    International Nuclear Information System (INIS)

    Quackenbush, E.; Clabby, M.; Gottesdiener, K.M.; Barbosa, J.; Jones, N.H.; Strominger, J.L.; Speck, S.; Leiden, J.M.

    1987-01-01

    Complementary DNA (cDNA) clones encoding the heavy chain of the heterodimeric human membrane glycoprotein 4F2 have been isolated by immunoscreening of a λgt11 expression library. The identity of these clones has been confirmed by hybridization to RNA and DNA prepared from mouse L-cell transfectants, which were produced by whole cell gene transfer and selected for cell-surface expression of the human 4F2 heavy chain. DNA sequence analysis suggest that the 4F2 heavy-chain cDNAs encode an approximately 526-amino acid type II membrane glycoprotein, which is composed of a large C-terminal extracellular domain, a single potential transmembrane region, and a 50-81 amino acid N-terminal intracytoplasmic domain. Southern blotting experiments have shown that the 4F2 heavy-chain cDNAs are derived from a single-copy gene that has been highly conserved during mammalian evolution

  2. Identification of phase I and II metabolites of the new designer drug α-pyrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).

    Science.gov (United States)

    Paul, Michael; Bleicher, Sergej; Guber, Susanne; Ippisch, Josef; Polettini, Aldo; Schultis, Wolfgang

    2015-11-01

    Pyrrolidinophenones represent one emerging class of newly encountered drugs of abuse, also known as 'new psychoactive substances', with stimulating psychoactive effects. In this work, we report on the detection of the new designer drug α-pyrrolidinohexiophenone (α-PHP) and its phase I and II metabolites in a human urine sample of a drug abuser. Determination and structural elucidation of these metabolites have been achieved by liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). By tentative identification, the exact and approximate structures of 19 phase I metabolites and nine phase II glucuronides were elucidated. Major metabolic pathways revealed the reduction of the ß-keto moieties to their corresponding alcohols, didesalkylation of the pyrrolidine ring, hydroxylation and oxidation of the aliphatic side chain leading to n-hydroxy, aldehyde and carboxylate metabolites, and oxidation of the pyrrolidine ring to its lactam followed by ring cleavage and additional hydroxylation, reduction and oxidation steps and combinations thereof. The most abundant phase II metabolites were glucuronidated ß-keto-reduced alcohols. Besides the great number of metabolites detected in this sample, α-PHP is still one of the most abundant ions together with its ß-keto-reduced alcoholic dihydro metabolite. Monitoring of these metabolites in clinical and forensic toxicology may unambiguously prove the abuse of the new designer drug α-PHP. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP(+)-induced cell death in human neuroblastoma SH-SY5Y cells: the impact of cell differentiation state.

    Science.gov (United States)

    Jantas, D; Greda, A; Golda, S; Korostynski, M; Grygier, B; Roman, A; Pilc, A; Lason, W

    2014-08-01

    Recent studies have documented that metabotropic glutamate receptors from group II and III (mGluR II/III) are a potential target in the symptomatic treatment of Parkinson's disease (PD), however, the neuroprotective effects of particular mGluR II/III subtypes in relation to PD pathology are recognized only partially. In the present study, we investigated the effect of various mGluR II/III activators in the in vitro model of PD using human neuroblastoma SH-SY5Y cell line and mitochondrial neurotoxin MPP(+). We demonstrated that all tested mGluR ligands: mGluR II agonist - LY354740, mGluR III agonist - ACPT-I, mGluR4 PAM - VU0361737, mGluR8 agonist - (S)-3,4-DCPG, mGluR8 PAM - AZ12216052 and mGluR7 allosteric agonist - AMN082 were protective against MPP(+)-evoked cell damage in undifferentiated (UN-) SH-SY5Y cells with the highest neuroprotection mediated by mGluR8-specific agents. However, in retinoic acid- differentiated (RA-) SH-SY5Y cells we found protection mediated only by mGluR8 activators. We also demonstrated the cell proliferation stimulating effect for mGluR4 and mGluR8 PAMs. Next, we showed that the protection mediated by mGluR II/III activators in UN-SH-SY5Y was not accompanied by the modulation of caspase-3 activity, however, a decrease in the number of apoptotic nuclei was found. Finally, we showed that the inhibitor of necroptosis, necrostatin-1 blocked the mGluR III-mediated protection. Altogether our comparative in vitro data add a further proof to neuroprotective effects of mGluR agonists or PAMs and point to mGluR8 as a promising target for neuroprotective interventions in PD. The results also suggest the participation of necroptosis-related molecular pathways in neuroprotective effects of mGluR III activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Synthesis, spectroscopic characterization of palladium(II)-orthohydroxyacetophenone azine nano-optical sensor doped in sol–gel matrix and its use as probe for assessment of α-amylase activity in human saliva

    Energy Technology Data Exchange (ETDEWEB)

    El-Sayed, B.A. [Chemistry department, Faculty of Science, al Azhr University, Cairo (Egypt); Abo-Aly, M.M., E-mail: aboalymoh@hotmail.com [Chemistry department, Faculty of Science, Ain Shams University, Cairo (Egypt); Attia, M.S.; Gamal, S. [Chemistry department, Faculty of Science, Ain Shams University, Cairo (Egypt)

    2016-01-15

    PdAPA (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel matrix is synthesized. It is characterized using UV-visible, infrared spectra and TEM image. A novel, simple, sensitive spectrofluorometric method was developed for measuring the activity of the α-amylase enzyme in human saliva for smokers and non-smokers with age range (17–64 years) based on the quenching of the luminescence intensity at 450 nm of the new synthesized complex characterized by various concentrations of the maltose released from the hydrolysis of starch by α-amylase enzyme and was successfully used as nano-optical sensor. The calibration plot was achieved over the concentration range 4.7×10{sup −6}–9.3×10{sup −10} mol L{sup −1} maltose with a correlation coefficient of 0.996 and a detection minimum limit value of 7.55×10{sup −10} mol L{sup −1}. The method was satisfactorily used for the assessment of the α-amylase activity in a number of human saliva samples for various smokers and non-smoker's volunteers. - Highlights: • The (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel was prepared. • It was used for the assessment of of α-amylase enzyme activity. • By maltose resulting from the reaction of α-amylase enzyme with starch. • A novel, simple, sensitive and precise spectrofluorometric method was developed.

  5. Chromogranin B and Secretogranin II in transgenic mice overexpressing human APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in Alzheimer patients.

    Science.gov (United States)

    Willis, Michael; Prokesch, Manuela; Hutter-Paier, Birgit; Windisch, Manfred; Stridsberg, Mats; Mahata, Sushil K; Kirchmair, Rudolf; Wietzorrek, Georg; Knaus, Hans-Günther; Jellinger, Kurt; Humpel, Christian; Marksteiner, Josef

    2008-03-01

    Chromogranin B and secretogranin II are major soluble constituents of large dense core vesicles of presynaptic structures and have been found in neuritic plaques of Alzheimer patients. We examined the distribution and expression of these peptides in both transgenic mice over expressing human amyloid-beta protein precursor APP751 with the London (V717I) and Swedish (K670M/N671L) mutations and in human post-mortem brain. In transgenic mice, the number of amyloid-beta plaques and chromogranin immunopositive plaques increased from 6 to 12 months. About 60% of amyloid-beta plaques were associated with chromogranin B and about 40% with secretogranin II. Chromogranin immunoreactivity appeared mainly as swollen dystrophic neurites. Neither synaptophysin- nor glial fibrillary acidic protein- immunoreactivity was expressed in chromogranin immunoreactive structures at any timepoint. Density of chromogranin peptides in hippocampal structures did not change in transgenic animals at any timepoint, even though animals had a poorer performance in the Morris water maze task. In conclusion, our findings in transgenic animals partly resembled findings in Alzheimer patients. Chromogranin peptides were associated with amyloid-beta plaques, but were not reduced in specific brain areas as previously reported by our group. Therefore specific changes of chromogranin peptides observed in Alzheimer patients can be related to amyloid-beta pathology only.

  6. Synthesis, spectroscopic characterization of palladium(II)-orthohydroxyacetophenone azine nano-optical sensor doped in sol–gel matrix and its use as probe for assessment of α-amylase activity in human saliva

    International Nuclear Information System (INIS)

    El-Sayed, B.A.; Abo-Aly, M.M.; Attia, M.S.; Gamal, S.

    2016-01-01

    PdAPA (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel matrix is synthesized. It is characterized using UV-visible, infrared spectra and TEM image. A novel, simple, sensitive spectrofluorometric method was developed for measuring the activity of the α-amylase enzyme in human saliva for smokers and non-smokers with age range (17–64 years) based on the quenching of the luminescence intensity at 450 nm of the new synthesized complex characterized by various concentrations of the maltose released from the hydrolysis of starch by α-amylase enzyme and was successfully used as nano-optical sensor. The calibration plot was achieved over the concentration range 4.7×10 −6 –9.3×10 −10 mol L −1 maltose with a correlation coefficient of 0.996 and a detection minimum limit value of 7.55×10 −10 mol L −1 . The method was satisfactorily used for the assessment of the α-amylase activity in a number of human saliva samples for various smokers and non-smoker's volunteers. - Highlights: • The (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel was prepared. • It was used for the assessment of of α-amylase enzyme activity. • By maltose resulting from the reaction of α-amylase enzyme with starch. • A novel, simple, sensitive and precise spectrofluorometric method was developed.

  7. Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.

    Science.gov (United States)

    Ding, Kang; Wang, Yan; Jiang, Weimin; Zhang, Yu; Yin, Hongping; Fang, Zhuyuan

    2015-03-25

    Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage. We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method. We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4. Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

  8. Residue Phe112 of the Human-Type Corrinoid Adenosyltransferase (PduO) Enzyme of Lactobacillus reuteri Is Critical to the Formation of the Four-Coordinate Co(II) Corrinoid Substrate and to the Activity of the Enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Mera, Paola E.; St. Maurice, Martin; Rayment, Ivan; Escalante-Semerena, Jorge C.; UW

    2009-06-08

    ATP:Corrinoid adenosyltransferases (ACAs) catalyze the transfer of the adenosyl moiety from ATP to cob(I)alamin via a four-coordinate cob(II)alamin intermediate. At present, it is unknown how ACAs promote the formation of the four-coordinate corrinoid species needed for activity. The published high-resolution crystal structure of the ACA from Lactobacillus reuteri (LrPduO) in complex with ATP and cob(II)alamin shows that the environment around the alpha face of the corrin ring consists of bulky hydrophobic residues. To understand how these residues promote the generation of the four-coordinate cob(II)alamin, variants of the human-type ACA enzyme from L. reuteri (LrPduO) were kinetically and structurally characterized. These studies revealed that residue Phe112 is critical in the displacement of 5,6-dimethylbenzimidazole (DMB) from its coordination bond with the Co ion of the ring, resulting in the formation of the four-coordinate species. An F112A substitution resulted in a 80% drop in the catalytic efficiency of the enzyme. The explanation for this loss of activity was obtained from the crystal structure of the mutant protein, which showed cob(II)alamin bound in the active site with DMB coordinated to the cobalt ion. The crystal structure of an LrPduO(F112H) variant showed a DMB-off/His-on interaction between the corrinoid and the enzyme, whose catalytic efficiency was 4 orders of magnitude lower than that of the wild-type protein. The analysis of the kinetic parameters of LrPduO(F112H) suggests that the F112H substitution negatively impacts product release. Substitutions of other hydrophobic residues in the Cbl binding pocket did not result in significant defects in catalytic efficiency in vitro; however, none of the variant enzymes analyzed in this work supported AdoCbl biosynthesis in vivo.

  9. Treatment of Mandibular Molar Class II Furcation Defects in Humans With Bovine Porous Bone Mineral in Combination With Plasma Rich in Growth Factors

    Directory of Open Access Journals (Sweden)

    S. Sadat Mansouri

    2012-01-01

    Full Text Available Objective: The purpose of the present randomized clinical trial study was to compare the effectiveness of Bovine Porous Bone Mineral (BPBM with and without Plasma Rich in Growth Factors (PRGF in the treatment of mandibular Class II furcation defects.Materials and Methods: In seven patients, nine pairs of symmetric buccal or lingual mandibular class II furcation defects were treated. In each patient, one defect received BPBM (control and the other received BPBM/PRGF (test by random assignment. Clinical measurements were made both at baseline and 6-month evaluation.Results: Similar improvements were observed with both treatment modalities.Significant reductions were gained in the gingival index, probing depth and relative vertical clinical attachment level. Plaque index and gingival recession changes were not significant in both groups. The mean probing depth reductions were 2.67±0.87 mm for the control group and 3.22±1.56 mm for the test group(p<0.001. The mean relative vertical clinical attachment level gains were 1.57±0.96 mm (p<0.001 and 1.65±1.24 mm (p<0.004 in the control and test groups, respectively. In the test group, the relative horizontal clinical attachment level reduced from 5.87±0.96 mm to 4.58±1.02 mm (p<0.02. No significant differenceswere observed in all clinical parameters 6 months postoperatively between the two groups.Conclusion: The application of a combined technique using BPBM/PRGF, compared to the BPBM alone, resulted in greater healing, although not significant, in the treatment of mandibular class II furcation defects.

  10. Mouse glutamate carboxypeptidaseII (GCPII) has a similar enzyme activity and inhibition profile but a different tissue distribution to human GCPII

    Czech Academy of Sciences Publication Activity Database

    Knedlík, Tomáš; Vorlová, Barbora; Navrátil, Václav; Tykvart, Jan; Sedlák, František; Vaculín, Š.; Franěk, M.; Šácha, Pavel; Konvalinka, Jan

    2017-01-01

    Roč. 7, č. 9 (2017), s. 1362-1378 ISSN 2211-5463 R&D Projects: GA ČR(CZ) GA16-02938S; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : glutamate carboxypeptidase II * mouse animal model * neuronal disorders * prostate cancer * prostate-specific membrane antigen Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.143, year: 2016 http://onlinelibrary.wiley.com/doi/10.1002/2211-5463.12276/full

  11. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-439 Small Diameter Bomb Increment II (SDB II) As of FY 2017 President’s Budget Defense... Bomb Increment II (SDB II) DoD Component Air Force Joint Participants Department of the Navy Responsible Office References SAR Baseline (Production...Mission and Description Small Diameter Bomb Increment II (SDB II) is a joint interest United States Air Force (USAF) and Department of the Navy

  12. Human decidua-derived mesenchymal stem cells differentiate into functional alveolar type II-like cells that synthesize and secrete pulmonary surfactant complexes.

    Directory of Open Access Journals (Sweden)

    Alejandro Cerrada

    Full Text Available Lung alveolar type II (ATII cells are specialized in the synthesis and secretion of pulmonary surfactant, a lipid-protein complex that reduces surface tension to minimize the work of breathing. Surfactant synthesis, assembly and secretion are closely regulated and its impairment is associated with severe respiratory disorders. At present, well-established ATII cell culture models are not available. In this work, Decidua-derived Mesenchymal Stem Cells (DMSCs have been differentiated into Alveolar Type II- Like Cells (ATII-LCs, which display membranous cytoplasmic organelles resembling lamellar bodies, the organelles involved in surfactant storage and secretion by native ATII cells, and accumulate disaturated phospholipid species, a surfactant hallmark. Expression of characteristic ATII cells markers was demonstrated in ATII-LCs at gene and protein level. Mimicking the response of ATII cells to secretagogues, ATII-LCs were able to exocytose lipid-rich assemblies, which displayed highly surface active capabilities, including faster interfacial adsorption kinetics than standard native surfactant, even in the presence of inhibitory agents. ATII-LCs could constitute a highly useful ex vivo model for the study of surfactant biogenesis and the mechanisms involved in protein processing and lipid trafficking, as well as the packing and storage of surfactant complexes.

  13. Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood

    International Nuclear Information System (INIS)

    Ovsyannikova, Inna G.; Johnson, Kenneth L.; Naylor, Stephen; Muddiman, David C.; Poland, Gregory A.

    2003-01-01

    This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines

  14. Safety and Efficacy of NEXT-II®, a Novel Water-Soluble, Undenatured Type II Collagen inHealthy Human SubjectsSuffering from Occasional Knee Joint Pain

    Directory of Open Access Journals (Sweden)

    Orie Yoshinari

    2015-07-01

    Full Text Available Background: Oral administration of a novel water-soluble undenatured type II collagen (NEXT-II® has been demonstrated to ameliorate the signs and symptoms of rheumatoid arthritis (RA in animal models. In the present investigation, we conducted a pilot study to examine the efficacy and safety of NEXT-II® in borderline subjects defined as healthy and non-diseased state, but with potential risks in knee joint health. Method: We employed Western Ontario McMaster Index (WOMAC score and Visual Analog Scale (VAS scores to assess the extent of improvement in the knee joints in these volunteers following supplementation of 40 mg NEXT-II® (10 mg as undenatured type II collagen over a period of 12 weeks. Result: The results demonstrated that NEXT-II® treatment significantly reduced WOMAC and VAS scores compared to subjects at baseline. Specifically, in the evaluation using VAS, the borderline subjects at resting, walking, and going up and down the stairs revealed significant improvement when compared to the baseline. Conclusion: The results of the studies demonstrated that NEXT-II® might be an ingredient which is safe and effective in the application of dietary supplement in ameliorating joint pain and symptoms of the borderline subjects without any adverse events.

  15. Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases.

    Science.gov (United States)

    Stephen, Selvaraj; Ambroise, Stanley; Pradeep, Jothimani; Gunasekaran, Dhandapany; Sangeetha, Balakrishnan; Sarangapani, Kengamuthu

    2017-09-01

    Seroprevalence of Q fever (QF) caused by Coxiella burnetii has been reported from different parts of India. Usually serological/molecular tests are employed for detection of infection. The present study was undertaken to verify the validity of three different QF phase II IgM ELISA kits for acute QF diagnosis by comparing with the gold standard indirect fluorescent antibody assay (IFA). Fifty eight serum samples collected from 42 patients (26 patients provided acute sample only and 16 both acute and convalescent samples) which were examined by all three commercial kits, were cross-checked with QF Phase II IgM IFA for confirmation. Eleven patients were positive for C. burnetii antibodies by IFA in acute and/or convalescent serum samples. Taking IFA as a reference, percentages of sensitivity, specificity, positive predictive value and negative predictive value for Virion-Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03, 84.62 and 100, 25.81, 32.35, 100 per cent, respectively. The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction.

  16. The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice

    DEFF Research Database (Denmark)

    Wintmo, P.; Johansen, S. H.; Hansen, P. B. L.

    2017-01-01

    Aim: The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. Methods: AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic...... minipumps for 4 weeks. Results: In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n = 7-9, P ... increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16 weeks (n = 13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes. Conclusion: AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse...

  17. Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part II. Effect of process variables on protein model drug encapsulation efficiency

    Czech Academy of Sciences Publication Activity Database

    Shubhra, Q. T. H.; Feczkó, T.; Kardos, A. F.; Tóth, J.; Macková, Hana; Horák, Daniel; Dósa, G.; Gyenis, J.

    2014-01-01

    Roč. 31, č. 2 (2014), s. 156-165 ISSN 0265-2048 R&D Projects: GA AV ČR(CZ) KAN401220801 Institutional support: RVO:61389013 Keywords : encapsulation efficiency * experimental design * human serum albumin Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 1.585, year: 2014

  18. Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies

    NARCIS (Netherlands)

    Steenbakkers, Peter G. A.; Baeten, Dominique; Rovers, Eric; Veys, Eric M.; Rijnders, Antonius W. M.; Meijerink, Jan; de Keyser, Filip; Boots, Annemieke M. H.

    2003-01-01

    Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta

  19. Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2010-01-01

    In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

  20. Human remains from the Moravian Gravettian. Morphology and taphonomy of additional elements from Dolní Vĕstonice II and Pavlov I

    Czech Academy of Sciences Publication Activity Database

    Trinkaus, E.; Svoboda, Jiří; Wojtal, P.; Nývltová Fišáková, Miriam; Wilczyński, J.

    2010-01-01

    Roč. 20, č. 6 (2010), s. 645-669 ISSN 1047-482X Institutional research plan: CEZ:AV0Z80010507 Keywords : Dolní Věstonice * Pavlov * Gravettian * human remains * morphology Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 0.802, year: 2010

  1. Determination of telmisartan in human blood plasma: Part II: Liquid chromatography-tandem mass spectrometry method development, comparison to immunoassay and pharmacokinetic study

    NARCIS (Netherlands)

    Hempen, C.M.; Gläsle-Schwarz, Liane; Kunz, Ulrich; Karst, U.

    2006-01-01

    A new liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) method with on-line sample clean-up for the determination of telmisartan in human blood plasma is presented. This technique is compared to a previously introduced enzyme-linked immunosorbent

  2. World Development Report, 1980. Part I: Adjustment and Growth in the 1980s. Part II: Poverty and Human Development. Annex: World Development Indicators. With Summary.

    Science.gov (United States)

    Isenman, Paul; And Others

    The report, third in a series of annual publications, examines some of the difficulties and prospects in areas of social and economic progress and human development which developing countries face during the next decade. Distinguishing oil-importing from oil-exporting developing countries, the first part of the report presents global and regional…

  3. Identification of mononuclear cells in human blood. II. Evaluation of morphological and immunological aspects of native and formaldehyde-fixed cell populations

    NARCIS (Netherlands)

    Schuit, H.R.E.; Hijmans, W.

    1980-01-01

    The presence of surface-associated immunoglobulins and Fc receptors on mononuclear cells from normal human blood waas investigated by the direct immunofluorescence technique combined with phase-contrast microscopy. Formaldehyde-fixed cells were compared to unfixed cells and to cells preincubated at

  4. Synovial Fluid Filtration by Articular Cartilage with a Worn-out Surface Zone in the Human Ankle Joint during Walking- II. Numerical Results for Steady Pure Sliding

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2000-01-01

    Roč. 45, č. 4 (2000), s. 375-396 ISSN 0001-7043 R&D Projects: GA ČR GA103/00/0008 Keywords : biphasic articular cartilage * biphasic synovial fluid * boundary lubrication * human ankle joint Subject RIV: BK - Fluid Dynamics

  5. Migration of the model HCR to the SAIC/TRC in the analysis of human reliability of the APS de CN Vandellos II

    International Nuclear Information System (INIS)

    Nos, V.; Rosa, J. C. de la; Hernandez, H.

    2011-01-01

    This paper describes the systematics of adaptation and conversion of models, to migrate the detailed analysis of human actions from the APS (in operation at power) of NPP Vandellos, which uses the HCR to SAIC-CRT model. Are offered the results achieved after the migration and the main conclusions.

  6. Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.

    Science.gov (United States)

    Fernandes, Ana S; Costa, Judite; Gaspar, Jorge; Rueff, José; Cabral, M Fátima; Cipriano, Madalena; Castro, Matilde; Oliveira, Nuno G

    2012-09-01

    The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.

  7. Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

    Science.gov (United States)

    Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

    2016-01-01

    Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

  8. A study of the human immune response to Lolium perenne (rye) pollen and its components, Lol p I and Lol p II (Rye I and Rye II). II. Longitudinal variation of antibody levels in relation to symptomatology and pollen exposure and correction of seasonally elevated antibody levels to basal values.

    Science.gov (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Marsh, D G

    1987-11-01

    This study used a standardized, dialyzed, Lolium perenne (ryegrass) pollen extract and two of its well-characterized components, Lol p I (Rye I) and Lol p II (Rye II), to characterize the longitudinal variation of both IgE and IgG antibody (Ab) levels, as well as total serum IgE levels, in 20 grass-allergic subjects followed for 13 months. Ab levels declined toward a basal level just before, and increased just after, the grass-pollination season, returning to the same basal level just before the next grass-pollination season. The least complex allergen, Lol II, demonstrated the most uniform pattern of variation in both IgE and IgG Ab levels. Total serum IgE levels demonstrated the least regular pattern of variation. Grass-pollen counts were strongly correlated with symptom-medication scores for these subjects (rs = 0.87). Initial values were correlated with the rise in total IgE and IgE Ab to Lol II across the grass-pollen season. Skin test results were correlated with initial IgE Ab levels for L. perenne pollen extract and Lol II. Finally, a procedure for correcting IgE Ab levels to basal values was proposed and tested. The correction procedure, for each IgE Ab, was based on the average rise during the grass-pollination season (or average decline after the grass-pollination season) observed for all subjects with that IgE Ab.

  9. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity; Desenvolvimento e padronizacao da tecnica de radioimunoensaio para a determinacao de pro-insulina humana e sua aplicacao no estudo do diabetes mellitus tipo II associado a obesidade

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Martha do

    1996-12-31

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of {beta} cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author) 133 refs., 17 figs., 36 tabs.

  10. Development and standardization of radioimmunoassay technique for human proinsulin determining and its use in the study of type II diabetes mellitus associated to obesity; Desenvolvimento e padronizacao da tecnica de radioimunoensaio para a determinacao de pro-insulina humana e sua aplicacao no estudo do diabetes mellitus tipo II associado a obesidade

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Martha do

    1997-12-31

    The availability of immunoassay methodology for proinsulin is important to define its physiological and pathophysiological significance in humans. Serum concentration of proinsulin are elevated in patients with type II Diabetes Mellitus (NIDDM) and recently diagnosed Type I, so a raised circulating concentration of proinsulin may serve as an early indicator of {beta} cells dysfunction. recently, in NIDDM the serum concentrations of proinsulin and its B-chain-C-peptide junctional split form, des (31-32), were found to correlate with diastolic blood pressure, a risk factor for cardiovascular disease. The development of a sensitive and specific radioimmunoassay (RIA) methodology for proinsulin has been difficult due to its low concentration in serum and the presence of proinsulin conversion intermediates in fluids and tissues. Also other potentially cross-reactive peptides, including insulin and C-peptide, can interfere in the assay. This work describe a highly specific human proinsulin RIA developed by using biosynthetic human proinsulin (hPI) as immunogen, standard and tracer. (author) 133 refs., 17 figs., 36 tabs.

  11. Topoisomerase II poisoning by indazole and imidazole complexes ...

    Indian Academy of Sciences (India)

    Unknown

    These molecules constitute two of the few most effective anticancer ruthenium compounds. ... however was hindered due to toxic side effects on the human body. Our ... cells. The catalytic cycle of topoisomerase II (topo II) typically involves ...

  12. Activation of Group II Metabotropic Glutamate Receptors Increases Proliferation but does not Influence Neuronal Differentiation of a Human Neural Stem Cell Line

    DEFF Research Database (Denmark)

    Dindler, Anne; Blaabjerg, Morten; Kamand, Morad

    2018-01-01

    of pharmacological activation and inhibition of mGluR2/3 on proliferation, differentiation and viability of a human neural stem cell line. Immunofluorescence staining revealed the presence of mGluR2/3 receptors on both proliferating and differentiating stem cells, including cells differentiated into β-tubulin III....... Western blot analysis revealed that the active, dimeric form of mGluR2/3 was mainly present on the proliferating cells, which may explain our findings. The present study emphasises the importance of glutamate and mGluRs on regulation of human neural stem cells and suggests a significant role of mGluR2....../3 during cell proliferation. This article is protected by copyright. All rights reserved....

  13. Tomo II

    OpenAIRE

    Llano Zapata, José Eusebio

    2015-01-01

    Memorias, histórico, físicas, crítico, apologéticas de la América Meridional con unas breves advertencias y noticias útiles, a los que de orden de Su Majestad hubiesen de viajar y describir aquellas vastas regiones. Reino Vegetal, Tomo II. Por un anónimo americano en Cádiz por los años de 1757. Muy Señor mío, juzgo que los 20 artículos del libro que remití a Vuestra Merced le habrán hecho formar el concepto que merece la fecundidad de aquellos países en las producciones minerales. Y siendo es...

  14. Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors

    OpenAIRE

    Wu, Shwu-Yuan; Zhou, Tianyuan; Chiang, Cheng-Ming

    2003-01-01

    Mediator is a general cofactor implicated in the functions of many transcriptional activators. Although Mediator with different protein compositions has been isolated, it remains unclear how Mediator facilitates activator-dependent transcription, independent of its general stimulation of basal transcription. To define the mechanisms of Mediator function, we isolated two forms of human Mediator complexes (Mediator-P.5 and Mediator-P.85) and demonstrated that Mediator-P.5 clearly functions by e...

  15. Modelling ecological and human exposure to POPs in Venice lagoon - Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models.

    Science.gov (United States)

    Radomyski, Artur; Giubilato, Elisa; Ciffroy, Philippe; Critto, Andrea; Brochot, Céline; Marcomini, Antonio

    2016-11-01

    The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The 'Phytoplankton', 'Aquatic Invertebrate', 'Fish', 'Human intake' and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. [Effect of Mn(II) on the error-prone DNA polymerase iota activity in extracts from human normal and tumor cells].

    Science.gov (United States)

    Lakhin, A V; Efremova, A S; Makarova, I V; Grishina, E E; Shram, S I; Tarantul, V Z; Gening, L V

    2013-01-01

    The DNA polymerase iota (Pol iota), which has some peculiar features and is characterized by an extremely error-prone DNA synthesis, belongs to the group of enzymes preferentially activated by Mn2+ instead of Mg2+. In this work, the effect of Mn2+ on DNA synthesis in cell extracts from a) normal human and murine tissues, b) human tumor (uveal melanoma), and c) cultured human tumor cell lines SKOV-3 and HL-60 was tested. Each group displayed characteristic features of Mn-dependent DNA synthesis. The changes in the Mn-dependent DNA synthesis caused by malignant transformation of normal tissues are described. It was also shown that the error-prone DNA synthesis catalyzed by Pol iota in extracts of all cell types was efficiently suppressed by an RNA aptamer (IKL5) against Pol iota obtained in our work earlier. The obtained results suggest that IKL5 might be used to suppress the enhanced activity of Pol iota in tumor cells.

  17. Urban and suburban malaria in Rondônia (Brazilian Western Amazon II: perennial transmissions with high anopheline densities are associated with human environmental changes

    Directory of Open Access Journals (Sweden)

    Luiz Herman Soares Gil

    2007-06-01

    Full Text Available Longitudinal entomological surveys were performed in Vila Candelária and adjacent rural locality of Bate Estaca concomitantly with a clinical epidemiologic malaria survey. Vila Candelária is a riverside periurban neighborhood of Porto Velho, capital of the state of Rondônia in the Brazilian Amazon. High anopheline densities were found accompanying the peak of rainfall, as reported in rural areas of the region. Moreover, several minor peaks of anophelines were recorded between the end of the dry season and the beginning of the next rainy season. These secondary peaks were related to permanent anopheline breeding sites resulting from human activities. Malaria transmission is, therefore, observed all over the year. In Vila Candelária, the risk of malaria infection both indoors and outdoors was calculated as being 2 and 10/infecting bites per year per inhabitant respectively. Urban malaria in riverside areas was associated with two factors: (1 high prevalence of asymptomatic carriers in a stable human population and (2 high anopheline densities related to human environmental changes. This association is probably found in other Amazonian urban and suburban communities. The implementation of control measures should include environmental sanitation and better characterization of the role of asymptomatic carriers in malaria transmission.

  18. Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice is Critical for Development and Function of Human T and B Cells

    Science.gov (United States)

    2011-05-17

    class switch was preserved in DRAG mice. The human identity of Ig heavy and Figure 4. Human T cells developed by DRAG mice are functional. At 6 months...HSC-infused DRAG and control mice were immunized with 1 flocculation unit of TT vaccine (Sanofi Pasteur ) by the intramuscular route, and the titers...and CD8 T cells with preserved integrity of both TCR and non-TCR signaling pathways. It has been suggested that low frequency and functional

  19. The evolution of myiasis in humans and other animals in the Old and New Worlds (part II): biological and life-history studies.

    Science.gov (United States)

    Stevens, Jamie R; Wallman, James F; Otranto, Domenico; Wall, Richard; Pape, Thomas

    2006-04-01

    Myiasis, which is the dipteran parasitism of living vertebrates, occurs in several forms - ranging from benign to fatal, opportunistic to obligate - and seems to have evolved through two distinct routes: saprophagous and sanguinivorous. However, the convergent evolution of morphological and life-history traits seems to have had a major role in confusing the overall picture of how myiasis evolved and this simplistic division is further complicated by the existence of both ectoparasitic and endoparasitic species of myiasis-causing Diptera, the evolutionary affinities of which remain to be resolved. As discussed in part I of this review, if we are to elucidate how the different forms of parasitism arose, it is essential to separate the evolution of the various groups of myiasis-causing flies from the evolution of the myiasis habit per se. Accordingly, whereas we focused on recent landmark phylogenetics studies in part I, we use this framework to analyse relevant biochemical, immunological, behavioural, biogeographical and fossil evidence to elucidate the evolution of myiasis in part II.

  20. Human leukocyte antigen class I, class II, and tumor necrosis factor-alpha polymorphisms in a healthy elder Mexican Mestizo population

    Directory of Open Access Journals (Sweden)

    Llorente Luis

    2005-11-01

    Full Text Available Abstract Background There is strong evidence that an individual's genetic background is an important predisposing factor to longevity. In the present study we analysed the frequency of HLA class I, class II, as well as the TNF-α -308 polymorphism that may be related to an increased life span in Mexican Mestizo healthy elders. Results HLA typing was performed by polymerase chain reaction sequence specific oligonucleotide (PCR SSO reverse dot blot. The TNF-α -308 polymorphism was assessed by PCR restriction fragment length polymorphism. A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males. The TNF2 allele was also increased in the elder group when compared to young controls. The frequencies of the remaining alleles tested were not statistically different among groups. Conclusion These data suggest an ethnicity independent tendency of HLA-DRB1*11 in elder females to increase life span and a possible role of the TNF2 allele with the successful remodelling of senescent immune system.

  1. Study comparing human papillomavirus (HPV) real-time multiplex PCR and Hybrid Capture II INNO-LiPA v2 HPV genotyping PCR assays

    DEFF Research Database (Denmark)

    Iftner, Thomas; Germ, Liesje; Swoyer, Ryan

    2009-01-01

    methods has not been well characterized. Clinically, cytology is used to establish possible HPV infection. We evaluated the sensitivity and specificity of HPV multiplex PCR assays compared to those of the testing scheme of the Hybrid Capture II (HCII) assay followed by an HPV PCR/line hybridization assay...... (HCII-LiPA v2). SurePath residual samples were split into two aliquots. One aliquot was subjected to HCII testing followed by DNA extraction and LiPA v2 genotyping. The second aliquot was shipped to a second laboratory, where DNA was extracted and HPV multiplex PCR testing was performed. Comparisons...... were evaluated for 15 HPV types common in both assays. A slightly higher proportion of samples tested positive by the HPV multiplex PCR than by the HCII-LiPA v2 assay. The sensitivities of the multiplex PCR assay relative to those of the HCII-LiPA v2 assay for HPV types 6, 11, 16, and 18, for example...

  2. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    OpenAIRE

    McMahon, Laura W.; Zhang, Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellu...

  3. Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Trier, Nicole; Gonzalez-Izarzugaza, Jose Maria; Chailyan, Anna

    2018-01-01

    influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred...... by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex...

  4. Interferon-β lipofection II. Mechanisms involved in cell death and bystander effect induced by cationic lipid-mediated interferon-β gene transfer to human tumor cells.

    Science.gov (United States)

    Villaverde, M S; Gil-Cardeza, M L; Glikin, G C; Finocchiaro, L M E

    2012-06-01

    We evaluated the cytotoxic effects (apoptosis, necrosis and early senescence) of human interferon-β (hIFNβ) gene lipofection. The cytotoxicity of hIFNβ gene lipofection resulted equivalent to that of the corresponding addition of the recombinant protein (rhIFNβ) on human tumor cell lines derived from Ewing's sarcoma (EW7 and COH) and colon (HT-29) carcinomas. However, it was stronger than rhIFNβ on melanoma (M8) and breast adenocarcinoma (MCF7). To reveal the mechanisms involved in these differences, we compared the effects of hIFNβ gene and rhIFNβ protein on EW7 and M8 (sensitive and resistant to rhIFNβ protein, respectively). Lipofection with hIFNβ gene caused a mitochondrial potential decrease simultaneous with an increase of oxidative stress in both cell lines. However, rhIFNβ protein displayed the same pattern of response only in EW7-sensitive cell line. The great bystander effect of the hIFNβ gene lipofection, involving the production of reactive oxygen species, would be among the main causes of its success. In EW7, this effect killed >60% of EW7 cell population, even though only 1% of cells were expressing the transgene. As hIFNβ gene was effective even in the rhIFNβ protein-resistant M8 cell line and in a way not limited by low lipofection efficiency, these results strongly support the clinical potential of this approach.

  5. Assessment of exposure to radio frequency electromagnetic fields from smart utility meters in GB; part II) numerical assessment of induced SAR within the human body.

    Science.gov (United States)

    Qureshi, Muhammad R A; Alfadhl, Yasir; Chen, Xiaodong; Peyman, Azadeh; Maslanyj, Myron; Mann, Simon

    2018-04-01

    Human body exposure to radiofrequency electromagnetic waves emitted from smart meters was assessed using various exposure configurations. Specific energy absorption rate distributions were determined using three anatomically realistic human models. Each model was assigned with age- and frequency-dependent dielectric properties representing a collection of age groups. Generalized exposure conditions involving standing and sleeping postures were assessed for a home area network operating at 868 and 2,450 MHz. The smart meter antenna was fed with 1 W power input which is an overestimation of what real devices typically emit (15 mW max limit). The highest observed whole body specific energy absorption rate value was 1.87 mW kg -1 , within the child model at a distance of 15 cm from a 2,450 MHz device. The higher values were attributed to differences in dimension and dielectric properties within the model. Specific absorption rate (SAR) values were also estimated based on power density levels derived from electric field strength measurements made at various distances from smart meter devices. All the calculated SAR values were found to be very small in comparison to International Commission on Non-Ionizing Radiation Protection limits for public exposure. Bioelectromagnetics. 39:200-216, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Direct extraction of lead (II) from untreated human blood serum using restricted access carbon nanotubes and its determination by atomic absorption spectrometry.

    Science.gov (United States)

    Barbosa, Valéria Maria Pereira; Barbosa, Adriano Francisco; Bettini, Jefferson; Luccas, Pedro Orival; Figueiredo, Eduardo Costa

    2016-01-15

    Oxidized carbon nanotubes were covered with layers of bovine serum albumin to result in so-called restricted-access carbon nanotubes (RACNTs). This material can extract Pb(2+) ions directly from untreated human blood serum while excluding all the serum proteins. The RACNTs have a protein exclusion capacity of almost 100% and a maximum Pb(2+) adsorption capacity of 34.5mg g(-1). High resolution transmission electron microscopy, scanning transmission electron microscopy and energy dispersive spectroscopy were used to confirm the BSA layer and Pb(2+) adsorption sites. A mini-column filled with RACNTs was used in an on-line solid phase extraction system coupled to a thermospray flame furnace atomic absorption spectrometry. At optimized experimental conditions, the method has a detection limit as low as 2.1µg L(-1), an enrichment factor of 5.5, and inter- and intra-day precisions (expressed as relative standard deviation) of <8.1%. Recoveries of the Pb(2+) spiked samples ranged from 89.4% to 107.3% for the extraction from untreated human blood serum. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. The inhibitory effect of angiotensin II type 1 receptor blocker combined with radiation on the proliferation and invasion ability of human nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Wang Qiong; Zhao Wei; Li Guiling; Zhang Sheng; Wu Gang

    2008-01-01

    Objective: To investigate the effect of valsartan, an angiotensin II type 1 receptor (AT1 R) blocker, on radiosensitivity, invasive potential and proliferation activity of nasopharyngeal carcinoma cells(CNE-2) in vitro. Methods: Radiosensitization of valsartan on CNE-2 cells in vitro was investigated by colony forming assay. Effect of AT1R blocker combined with radiation on invasive potential of CNE-2 cells was evaluated using 24-well Matrigel invasion chambers (Transwell). Apoptosis-inducing effect of valsartan combined with radiation on apoptosis of CNE-2 was identified by flow cytometry (FCM). Results: When valsartan was given at 10 -9 , 10 -8 and 10 -7 mol/L combined with radiation, sensitivity enhancement ratios (SER) were 1.10, 1.20 and 1.36, and the invasive inhibition rates were 8.11%, 16.49% and 16.77%, respectively. The SER of valsartan on CNE-2 distinctly increased when the exposure time was increased. After 24 h exposure to 10 -8 mol/L valsartan combined with radiation, the apoptosis rate was 1.89% ± 0.09%, which was higher than 1.62% ± 0.06% in radiation alone group (t=4.79, P<0.05). Conclusions: AT1R blocker valsartan combined with radiation can significantly inhibit the proliferation activity of nasopharyngeal carcinoma cells in vitro in a dose- and time-dependent manner. Valsartan combined with radiation can potently inhibit the invasive potential of CNE-2, which may be involved in the mechanism of valsartan treatment in vivo. (authors)

  8. DJ-1 Modulates Nuclear Erythroid 2–Related Factor-2–Mediated Protection in Human Primary Alveolar Type II Cells in Smokers

    Science.gov (United States)

    Bahmed, Karim; Messier, Elise M.; Zhou, Wenbo; Tuder, Rubin M.; Freed, Curt R.; Chu, Hong Wei; Kelsen, Steven G.; Bowler, Russell P.; Mason, Robert J.

    2016-01-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2–related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases. PMID:27093578

  9. Human T-cell lymphotropic virus types I and II infections in a cohort of patients with neurological disorders in Belém, Pará, Brazil Infecção pelos vírus linfotrópicos humanos de células T tipos I e II entre pacientes com doença neurológica em Belém, Pará, Brasil

    Directory of Open Access Journals (Sweden)

    Olinda Macêdo

    2004-02-01

    Full Text Available Serum- and/or- cerebrospinal fluid (CSF samples obtained from 190 patients suffering from chronic, progressive neurological disease were screened for the presence of human T-cell lymphotropic viruses type I (HTLV-I and type II (HTLV-II antibodies over a six-year period (1996 to 2001 in Belém, Pará, Brazil. Patients were of both sexes (male subjects, 52% with ages ranging from 2 to 79 years (mean, 35.9. Overall, 15 (7.9% subjects - of whom 12 (80% were female adults - reacted HTLV-I/II-seropositive when screened by enzyme-linked immunosorbent assay (ELISA. Serum samples from 14 of these patients were also analyzed using a recombinant Western blot (WB assay that yielded HTLV-I-, HTLV-II-, and HTLV-I/II- reactivities for 10 (71.4%, 3 (21.4% and 1 (7.2% of them, respectively. The yearly rates of HTLV-I/II antibodies ranged from 2.6% (2001 to 21.7% (2000, with progressively increasing seropositivities from 1998 to 2000. Altogether, walking difficulty (n = 5 subjects, spasticity (n = 4 and leg weakness (n = 3 accounted for 80% of symptoms recorded among the 15 patients whose sera had antibodies to HTLV-I/II as detected by ELISA. These findings provide evidence that both HTLV-I and HTLV-II play a role in the development of chronic myelopathy in Belém, Pará, Northern Brazil.Amostras de soro e/ou líquido céfalo-raquidiano (LCR foram obtidas de 190 pacientes com quadro de doença neurológica crônica e progressiva, com vistas à detecção de anticorpos para os vírus linfotrópicos humanos de células T dos tipos I (HTLV-I e II (HTLV-II, durante um período de seis anos (1996 a 2001 em Belém, Pará, Brasil. O grupo compreendia ambos os sexos (homens, 52%, com idades variando de 2 a 79 anos (média, 35,9 anos. Tomando-se os resultados como um todo, 15 (7,9% indivíduos, incluindo 12 (80% mulheres adultas, apresentaram anticorpos para HTLV-I/II a partir da triagem pelo procedimento imunoenzimático (ELISA. Soros de 14 desses pacientes também foram

  10. NNDSS - Table II. Babesiosis to Campylobacteriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Babesiosis to Campylobacteriosis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  11. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  12. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  13. NNDSS - Table II. Shiga toxin to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Shiga toxin to Shigellosis - 2015. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  14. NNDSS - Table II. West Nile virus disease

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. West Nile virus disease - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  15. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  16. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  17. NNDSS - Table II. Mumps to Rabies, animal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Mumps to Rabies, animal - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  18. NNDSS - Table II. Legionellosis to Malaria

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Legionellosis to Malaria - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  19. NNDSS - Table II. Hepatitis (viral, acute) C

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) C - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  20. NNDSS - Table II. Babesiosis to Campylobacteriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Babesiosis to Campylobacteriosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  1. NNDSS - Table II. West Nile virus disease

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. West Nile virus disease - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  2. NNDSS - Table II. Giardiasis to Haemophilus influenza

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  3. NNDSS - Table II. Meningococcal to Pertussis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal to Pertussis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  4. NNDSS - Table II. Ehrlichiosis and Anaplasmosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Ehrlichiosis and Anaplasmosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  5. NNDSS - Table II. Cryptosporidiosis to Dengue

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Cryptosporidiosis to Dengue - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  6. NNDSS - Table II. Tetanus to Varicella

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Tetanus to Varicella - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  7. NNDSS - Table II. Chlamydia to Coccidioidomycosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Chlamydia to Coccidioidomycosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  8. NNDSS - Table II. Salmonellosis to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Salmonellosis to Shigellosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  9. NNDSS - Table II. West Nile to Zika

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. West Nile to Zika - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and...

  10. NNDSS - Table II. Babesiosis to Coccidioidomycosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Babesiosis to Coccidioidomycosis - 2014.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  11. NNDSS - Table II. Giardiasis to Haemophilus influenza

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2014. In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000...

  12. NNDSS - Table II. Giardiasis to Haemophilus influenza

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  13. NNDSS - Table II. Giardiasis to Haemophilus influenza

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  14. NNDSS - Table II. Giardiasis to Haemophilus influenza

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Giardiasis to Haemophilus influenza - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  15. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  16. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  17. NNDSS - Table II. Hepatitis (viral, acute)

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Hepatitis (viral, acute) - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases but...

  18. NNDSS - Table II. Meningococcal disease to Pertussis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Meningococcal disease to Pertussis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  19. NNDSS - Table II. Chlamydia to Coccidioidomycosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Chlamydia to Coccidioidomycosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  20. NNDSS - Table II. Tetanus to Varicella

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Tetanus to Varicella - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  1. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals...

  2. NNDSS - Table II. Legionellosis to Malaria

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Legionellosis to Malaria - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  3. NNDSS - Table II. Lyme disease to Meningococcal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  4. NNDSS - Table II. Lyme disease to Meningococcal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2014In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases...

  5. NNDSS - Table II. Lyme disease to Meningococcal

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Lyme disease to Meningococcal - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  6. NNDSS - Table II. Salmonellosis to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Salmonellosis to Shigellosis - 2014.In this Table, all conditions with a 5-year average annual national total of more than or equals 1,000 cases...

  7. NNDSS - Table II. West Nile virus disease

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. West Nile virus disease - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  8. NNDSS - Table II. Rubella to Salmonellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Rubella to Salmonellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  9. NNDSS - Table II. Ehrlichiosis/Anaplasmosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Ehrlichiosis/Anaplasmosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  10. NNDSS - Table II. Tetanus to Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Tetanus to Vibriosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding year),...

  11. NNDSS - Table II. Shiga toxin to Shigellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Shiga toxin to Shigellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  12. NNDSS - Table II. Babesiosis to Campylobacteriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Babesiosis to Campylobacteriosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  13. NNDSS - Table II. Babesiosis to Campylobacteriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Babesiosis to Campylobacteriosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  14. NNDSS - Table II. Rubella to Salmonellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Rubella to Salmonellosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year),...

  15. NNDSS - Table II. Tetanus to Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Tetanus to Vibriosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and...

  16. NNDSS - Table II. Chlamydia to Coccidioidomycosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Chlamydia to Coccidioidomycosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding...

  17. NNDSS - Table II. Ehrlichiosis/Anaplasmosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Ehrlichiosis/Anaplasmosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the preceding...

  18. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2015.In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  19. NNDSS - Table II. Invasive Pneumococcal to Legionellosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal to Legionellosis - 2016. In this Table, provisional* cases of selected† notifiable diseases (≥1,000 cases reported during the...

  20. Human placental growth hormone, insulin-like growth factor I and -II, and insulin requirements during pregnancy in type 1 diabetes

    DEFF Research Database (Denmark)

    Fuglsang, Jens; Lauszus, Finn; Flyvbjerg, Allan

    2003-01-01

    between hPGH and IGF-I in type 1 diabetes mellitus has not been investigated thoroughly. Furthermore, hPGH may be involved in the development of insulin resistance during pregnancy. In this prospective, longitudinal study, 51 type 1 diabetic subjects were followed with repeated blood sampling during...... pregnancy in type 1 diabetic subjects could not be related to hPGH levels.......Human placental GH (hPGH) replaces pituitary GH during pregnancy. hPGH is correlated to serum IGF-I in normal pregnancies and in pregnancies complicated by fetoplacental disorders. In gestational diabetes and type 2 diabetes no correlation between hPGH and IGF-I has been found. The relationship...

  1. Household exposure to violence and human rights violations in western Bangladesh (II: history of torture and other traumatic experience of violence and functional assessment of victims

    Directory of Open Access Journals (Sweden)

    Biswas Shuvodwip

    2009-11-01

    Full Text Available Abstract Background Organised crime and political violence (OPV and human rights violations have marred Bangladesh history since 1971. Little is known about the consequences for the oppressed population. This study describes the patterns of OPV and human rights violations in a disturbed area of Bangladesh and assesses the physical, emotional and social functioning of victims. Methods A total of 236 of selected participants in a household survey in Meherpur district were recruited for a detailed study. Interviews and physical examinations were used to obtain information about history of torture and other cruel, inhuman or degrading treatment or punishment (TCIDTP, and about injuries, pain frequency and intensity. Handgrip strength and standing balance performance were measured. The "WHO-5 Well-being" scale was used to assess the subjective emotional well-being of study participants. Results The majority of the reported cases of TCIDTP occurred in 2000-2008, 51% of incidents occurred during winter; 32.0% between 20:00 and midnight. Police involvement was reported in 75% of cases. Incidents took place at victims' homes (46.7%, or at the police station, military camp, in custody or in prison (21.9%. Participants experienced 1-10 TCIDTP methods and reported 0-6 injury locations on their bodies; 77.5% reported having at least two injuries. Less than half of the participants were able to stand on one leg for 30 seconds. Only 7.5% of males aged 25-44 had handgrip strength in both hands exceeding average values for healthy people at the same age. Over 85% of participants scored low ( Conclusion A detailed picture of characteristics of the victimisation is presented. The participants showed poor emotional well-being and reduced physical capacity. The results indicated that the simple and rapid method of assessment used here is a promising tool that could be used to monitor the quality and outcome of rehabilitation.

  2. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

    Science.gov (United States)

    Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

    2015-06-27

    The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT). II. An inter-laboratory study of the h-CLAT.

    Science.gov (United States)

    Sakaguchi, H; Ashikaga, T; Miyazawa, M; Yoshida, Y; Ito, Y; Yoneyama, K; Hirota, M; Itagaki, H; Toyoda, H; Suzuki, H

    2006-08-01

    Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen

  4. Dose-response relationship of dicentric chromosomes in human lymphocytes obtained for the fission neutron therapy facility MEDAPP at the research reactor FRM II.

    Science.gov (United States)

    Schmid, E; Wagner, F M; Romm, H; Walsh, L; Roos, H

    2009-02-01

    The biological effectiveness of neutrons from the neutron therapy facility MEDAPP (mean neutron energy 1.9 MeV) at the new research reactor FRM II at Garching, Germany, has been analyzed, at different depths in a polyethylene phantom. Whole blood samples were exposed to the MEDAPP beam in special irradiation chambers to total doses of 0.14-3.52 Gy at 2-cm depth, and 0.18-3.04 Gy at 6-cm depth of the phantom. The neutron and gamma-ray absorbed dose rates were measured to be 0.55 Gy min(-1) and 0.27 Gy min(-1) at 2-cm depth, while they were 0.28 and 0.25 Gy min(-1) at 6-cm depth. Although the irradiation conditions at the MEDAPP beam and the RENT beam of the former FRM I research reactor were not identical, neutrons from both facilities gave a similar linear-quadratic dose-response relationship for dicentric chromosomes at a depth of 2 cm. Different dose-response curves for dicentrics were obtained for the MEDAPP beam at 2 and 6 cm depth, suggesting a significantly lower biological effectiveness of the radiation with increasing depth. No obvious differences in the dose-response curves for dicentric chromosomes estimated under interactive or additive prediction between neutrons or gamma-rays and the experimentally obtained dose-response curves could be determined. Relative to (60)Co gamma-rays, the values for the relative biological effectiveness at the MEDAPP beam decrease from 5.9 at 0.14 Gy to 1.6 at 3.52 Gy at 2-cm depth, and from 4.1 at 0.18 Gy to 1.5 at 3.04 Gy at 6-cm depth. Using the best possible conditions of consistency, i.e., using blood samples from the same donor and the same measurement techniques for about two decades, avoiding the inter-individual variations in sensitivity or the differences in methodology usually associated with inter-laboratory comparisons, a linear-quadratic dose-response relationship for the mixed neutron and gamma-ray MEDAPP field as well as for its fission neutron part was obtained. Therefore, the debate on whether the fission

  5. Efficiency of Chitosan for the Removal of Pb (II, Fe (II and Cu (II Ions from Aqueous Solutions

    Directory of Open Access Journals (Sweden)

    Soheil Sobhanardakani

    2014-09-01

    Full Text Available Background: Heavy metals have been recognized as harmful environmental pollutant known to produce highly toxic effects on different organs and systems of both humans and animals. The aim of this paper is to evaluate the adsorption potential of chitosan for the removal of Pb(II, Fe(II and Cu(II ions from aqueous solutions. Methods: This study was conducted in laboratory scale. In this paper chitosan has been used as an adsorbent for the removal of Pb(II, Fe(II and Cu(II from aqueous solution. In batch tests, the effects of parameters like pH solution (1.0-8.0, initial metal concentrations (100-1000 mgL-1, contact time (5.0-150 min and adsorbent dose (1.0-7.0 g on the adsorption process were studied. Results: The results showed that the adsorption of Pb(II, Fe(II and Cu(II ions on chitosan strongly depends on pH. The experimental isothermal data were analyzed using the Langmuir and Freundlich equations and it was found that the removal process followed the Langmuir isotherm and maximum adsorption capacity for the adsorption of Pb(II, Fe(II and Cu(II ions by the chitosan were 55.5mg g−1, 71.4 mg g−1 and 59 mg g−1, respectively, under equilibrium conditions at 25±1 ºC. The adsorption process was found to be well described by the pseudo-second-order rate model. Conclusion: The obtained results showed that chitosan is a readily, available, economic adsorbent and was found suitable for removing Pb(II, Fe(II and Cu(II ions from aqueous solution.

  6. Determination of barium in natural waters by ICP-OES technique. Part II: Assessment of human exposure to barium in bottled mineral and spring waters produced in Poland.

    Science.gov (United States)

    Garboś, Sławomir; Swiecicka, Dorota

    2013-01-01

    A method of the classification of natural mineral and spring waters and maximum admissible concentration (MAC) levels of metals present in such types of waters are regulated by Commission Directive 2003/40/EC, Directive 2009/54/EC of the European Parliament and of the Council and Ordinance of Minister of Health of 30 March 2011 on the natural mineral waters, spring waters and potable waters. MAC of barium in natural mineral and spring waters was set at 1.0 mg/l, while World Health Organization determined the Ba guideline value in water intended for human consumption at the level of 0.7 mg/l. The aims of the study were: the determination of barium in natural mineral and spring waters (carbonated, non-carbonated and medium-carbonated waters) produced and bottled on the area of Poland, and assessment of human exposure to this metal presents in the above-mentioned types of waters. The study concerning barium determinations in 23 types of bottled natural mineral waters and 15 types of bottled spring waters (bought in Polish retail outlets) was conducted in 2010. The analyses were performed by validated method of determination of barium in water based on inductively coupled plasma optical emission spectrometry, using modern internal quality control scheme. Concentrations of barium determined in natural mineral and spring waters were in the ranges from 0.0136 mg/l to 1.12 mg/l and from 0.0044 mg/l to 0.43 mg/l, respectively. Only in the single case of natural mineral water the concentration of barium (1.12 mg/l), exceeded above-mentioned MAC for this metal, which is obligatory in Poland and the European Union - 1.0 mg/l. The long-term monitoring of barium concentration in another natural mineral water (2006 - 2010), in which incidental exceeding MAC was observed in 2006, was conducted. All measured barium concentrations in this water were lower than 1.0 mg/l and therefore, it is possible to state that the proper method of mixing waters taken from six independent

  7. Cd(II), Cu(II)

    African Journals Online (AJOL)

    user

    Depending on the way goethite was pretreated with oxalic acid, affinity for Cd(II) varied ...... Effects and mechanisms of oxalate on Cd(II) adsorption on goethite at different ... precipitation, surfactant mediation, hydrothermal and micro-emulsion.

  8. Household exposure to violence and human rights violations in western Bangladesh (II): history of torture and other traumatic experience of violence and functional assessment of victims

    Science.gov (United States)

    2009-01-01

    Background Organised crime and political violence (OPV) and human rights violations have marred Bangladesh history since 1971. Little is known about the consequences for the oppressed population. This study describes the patterns of OPV and human rights violations in a disturbed area of Bangladesh and assesses the physical, emotional and social functioning of victims. Methods A total of 236 of selected participants in a household survey in Meherpur district were recruited for a detailed study. Interviews and physical examinations were used to obtain information about history of torture and other cruel, inhuman or degrading treatment or punishment (TCIDTP), and about injuries, pain frequency and intensity. Handgrip strength and standing balance performance were measured. The "WHO-5 Well-being" scale was used to assess the subjective emotional well-being of study participants. Results The majority of the reported cases of TCIDTP occurred in 2000-2008, 51% of incidents occurred during winter; 32.0% between 20:00 and midnight. Police involvement was reported in 75% of cases. Incidents took place at victims' homes (46.7%), or at the police station, military camp, in custody or in prison (21.9%). Participants experienced 1-10 TCIDTP methods and reported 0-6 injury locations on their bodies; 77.5% reported having at least two injuries. Less than half of the participants were able to stand on one leg for 30 seconds. Only 7.5% of males aged 25-44 had handgrip strength in both hands exceeding average values for healthy people at the same age. Over 85% of participants scored low (political involvement, personal conflicts and the fear of neighbourhood violence strongly affected emotional well-being. Good emotional well-being correlated with increased political and social participation. Conclusion A detailed picture of characteristics of the victimisation is presented. The participants showed poor emotional well-being and reduced physical capacity. The results indicated that

  9. Household exposure to violence and human rights violations in western Bangladesh (II): history of torture and other traumatic experience of violence and functional assessment of victims.

    Science.gov (United States)

    Wang, Shr-Jie; Haque, Mohammad Akramul; Masum, Saber-Ud-Daula; Biswas, Shuvodwip; Modvig, Jens

    2009-11-27

    Organised crime and political violence (OPV) and human rights violations have marred Bangladesh history since 1971. Little is known about the consequences for the oppressed population. This study describes the patterns of OPV and human rights violations in a disturbed area of Bangladesh and assesses the physical, emotional and social functioning of victims. A total of 236 of selected participants in a household survey in Meherpur district were recruited for a detailed study. Interviews and physical examinations were used to obtain information about history of torture and other cruel, inhuman or degrading treatment or punishment (TCIDTP), and about injuries, pain frequency and intensity. Handgrip strength and standing balance performance were measured. The "WHO-5 Well-being" scale was used to assess the subjective emotional well-being of study participants. The majority of the reported cases of TCIDTP occurred in 2000-2008, 51% of incidents occurred during winter; 32.0% between 20:00 and midnight. Police involvement was reported in 75% of cases. Incidents took place at victims' homes (46.7%), or at the police station, military camp, in custody or in prison (21.9%). Participants experienced 1-10 TCIDTP methods and reported 0-6 injury locations on their bodies; 77.5% reported having at least two injuries. Less than half of the participants were able to stand on one leg for 30 seconds. Only 7.5% of males aged 25-44 had handgrip strength in both hands exceeding average values for healthy people at the same age. Over 85% of participants scored low (<13) on the 25-point "WHO-5 Well-being" scale. The number of years since the TCIDTP event, pain frequency, the need to quit a job to take care of an injured family member, political involvement, personal conflicts and the fear of neighbourhood violence strongly affected emotional well-being. Good emotional well-being correlated with increased political and social participation. A detailed picture of characteristics of the

  10. Zeolite scaffolds for cultures of human breast cancer cells. Part II: Effect of pure and hybrid zeolite membranes on neoplastic and metastatic activity control.

    Science.gov (United States)

    Tavolaro, Palmira; Martino, Guglielmo; Andò, Sebastiano; Tavolaro, Adalgisa

    2016-11-01

    This work is focused on the response of two invasive phenotypes of human breast cancer cells, MCF-7 and MDA-MB-231, grown on synthesized zeolite scaffolds in order to study the influence of those biomaterials in controlled conditions with and without anti-tumoral drug treatments. Our research was directed to the use of doxorubicin (DOX) and bergapten (5-MOP). The former is broadly considered the most active single agent available for the treatment of breast cancer, the second is a natural psoralen with an apoptotic effect. The results indicate that both drugs inhibit the cell viability of all cell lines grown on all zeolite scaffolds and that all Pure Zeolite Membranes are more responsive with respect to all Mixed Matrix Membranes. Moreover, the results after treatment with DOX at a concentration of 7.4μM for 24h, show that the expression of the matrix metalloproteinases (MMP-2 and MMP-9) is greatly reduced in both cell lines, especially in those adherent on Pure Zeolite Scaffolds. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Knockdown of αII spectrin in normal human cells by siRNA leads to chromosomal instability and decreased DNA interstrand cross-link repair

    International Nuclear Information System (INIS)

    McMahon, Laura W.; Zhang Pan; Sridharan, Deepa M.; Lefferts, Joel A.; Lambert, Muriel W.

    2009-01-01

    Nonerythroid α-spectrin (αIISp) is a structural protein involved in repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), which are defective in ability to repair cross-links. In order to further demonstrate the importance of the role that αIISp plays in normal human cells and in the repair defect in FA, αIISp was knocked down in normal cells using siRNA. Depletion of αIISp in normal cells by siRNA resulted in chromosomal instability and cellular hypersensitivity to DNA interstrand cross-linking agents. An increased number of chromosomal aberrations were observed and, following treatment with a DNA interstrand cross-linking agent, mitomycin C, cells showed decreased cell growth and survival and decreased formation of damage-induced αIISp and XPF nuclear foci. Thus depletion of αIISp in normal cells leads to a number of defects observed in FA cells, such as chromosome instability and a deficiency in cross-link repair.

  12. A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease.

    Science.gov (United States)

    Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme

    2009-02-01

    The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

  13. The Role of Damage-Associated Molecular Patterns (DAMPs in Human Diseases; Part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine

    Directory of Open Access Journals (Sweden)

    Walter G. Land

    2015-05-01

    Full Text Available This article is the second part of a review that addresses the role of damage-associated molecular patterns (DAMPs in human diseases by presenting examples of traumatic (systemic inflammatory response syndrome, cardiovascular (myocardial infarction, metabolic (type 2 diabetes mellitus, neurodegenerative (Alzheimer’s disease, malignant and infectious diseases. Various DAMPs are involved in the pathogenesis of all these diseases as they activate innate immune machineries including the unfolded protein response and inflammasomes. These subsequently promote sterile autoinflammation accompanied, at least in part, by subsequent adaptive autoimmune processes. This review article discusses the future role of DAMPs in routine practical medicine by highlighting the possibility of harnessing and deploying DAMPs either as biomarkers for the appropriate diagnosis and prognosis of diseases, as therapeutics in the treatment of tumours or as vaccine adjuncts for the prophylaxis of infections. In addition, this article examines the potential for developing strategies aimed at mitigating DAMPs-mediated hyperinflammatory responses, such as those seen in systemic inflammatory response syndrome associated with multiple organ failure.

  14. Fused pyrazine mono-N-oxides as bioreductive drugs. II cytotoxicity in human cells and oncogenicity in a rodent transformation assay

    International Nuclear Information System (INIS)

    Langmuir, Virginia K.; Laderoute, Keith R.; Mendonca, Holly L.; Sutherland, Robert M.; Hei, Tom K.; Liu, S.-X.; Hall, Eric J.; Naylor, Matthew A.; Adams, Gerald E.

    1996-01-01

    Purpose: To determine what structural moieties of the fused pyrazine mono-N-oxides are determining factors in their in vitro cytotoxicity and oncogenicity. Methods and Materials: A new series of experimental bioreductive drugs, fused pyrazine mono-N-oxides, was evaluated in vitro for aerobic and hypoxic cytotoxicity in the HT29 human colon adenocarcinoma cell line by using clonogenic assays. The relative oncogenicities of these compounds were also determined in aerobic cultures of C3H 10T1/2 mouse embryo fibroblasts by using a standard transformation assay. Results: Removal of the 4-methyl piperazine side chain from the parent compound, RB 90740, reduced the potency of the hypoxic cytotoxin. Reduction of the N-oxide function increased the aerobic cytotoxicity and eliminated most of the hypoxic/aerobic cytotoxic differential. The reduced N-oxide also had significant oncogenicity, consistent with a mechanism of genotoxicity following bioreduction of RB 90740. Conclusion: This new series of bioreductive compounds may be effective in cancer therapy, particularly the lead compound RB 90740. The oncogenic potential of these compounds is similar to that for other cancer therapies. Further studies should include evaluation of these compounds in vivo and the development of analogs with reduced oncogenic potential and retention of the hypoxic/aerobic cytotoxicity differential

  15. Cu(II) AND Zn(II)

    African Journals Online (AJOL)

    Preferred Customer

    SYNTHESIS OF 2,2-DIMETHYL-4-PHENYL-[1,3]-DIOXOLANE USING ZEOLITE. ENCAPSULATED Co(II), Cu(II) AND Zn(II) COMPLEXES. B.P. Nethravathi1, K. Rama Krishna Reddy2 and K.N. Mahendra1*. 1Department of Chemistry, Bangalore University, Bangalore-560001, India. 2Department of Chemistry, Government ...

  16. Elizabeth II uus kunstigalerii

    Index Scriptorium Estoniae

    1999-01-01

    Tähistamaks oma troonile asumise 50. aastapäeva, avab Elizabeth II 6. II 2002 Buckinghami palees uue kunstigalerii, mis ehitatakse palee tiibhoonena. Arhitekt John Simpson. Elizabeth II kunstikogust

  17. The enigma of capitalism - Beyond human power II and John Gabriel Borkman. Bjørnstjere Bjørnson and Henrik Ibsen as critics of capitalism

    Directory of Open Access Journals (Sweden)

    Fredrik Engelstad

    2015-02-01

    Full Text Available The mid-1890s saw the publication of two seminal critiques of capitalism in Norwegian drama: Bjørnstjerne Bjørnson’s Beyond Human Power – Second Play (1895, and Henrik Ibsen’s John Gabriel Borkman (1896. The obvious differences, as well as the similarities of these plays, invite a comparative analysis. Bjørnson’s play is a sociological depiction of class differences and class struggles, expressed in collective action strategies by employers, and a strange mixture of powerlessness and terrorism by the working class.  The main references are work relations and social and political collectivities. Nevertheless, identities and close social relations are a necessary part of social structures as well as dramatic plots. The analysis of Bjørnson’s play focuses on the relationships between individual lives and individual action on the one hand, and the broad social landscape on the other. John Gabriel Borkman is about a stagnated universe, where all of the main characters are trying to revive the past. Borkman is not about work and collectivities, but about financial capital. To Ibsen, financial capital is the ideal environment for research on the ambitions and shortcomings of individuals. Finance in one sense leads to the aggrandizement of individual power; it makes possible the idea that one man can rule the world. At the same time, there is a world of production in the Ibsenesque universe, as there is a world of social identities in Bjørnson. The inspiration for both plays may be found in the developments of capitalism during the latter half of the nineteenth century, but also in their intertextual relationships with Nietzsche and Goethe’s Faust.

  18. Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends.

    Science.gov (United States)

    Chuzhanova, Nadia; Abeysinghe, Shaun S; Krawczak, Michael; Cooper, David N

    2003-09-01

    Translocations and gross deletions are responsible for a significant proportion of both cancer and inherited disease. Although such gene rearrangements are nonuniformly distributed in the human genome, the underlying mutational mechanisms remain unclear. We have studied the potential involvement of various types of repetitive sequence elements in the formation of secondary structure intermediates between the single-stranded DNA ends that recombine during rearrangements. Complexity analysis was used to assess the potential of these ends to form secondary structures, the maximum decrease in complexity consequent to a gross rearrangement being used as an indicator of the type of repeat and the specific DNA ends involved. A total of 175 pairs of deletion/translocation breakpoint junction sequences available from the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] were analyzed. Potential secondary structure was noted between the 5' flanking sequence of the first breakpoint and the 3' flanking sequence of the second breakpoint in 49% of rearrangements and between the 5' flanking sequence of the second breakpoint and the 3' flanking sequence of the first breakpoint in 36% of rearrangements. Inverted repeats, inversions of inverted repeats, and symmetric elements were found in association with gross rearrangements at approximately the same frequency. However, inverted repeats and inversions of inverted repeats accounted for the vast majority (83%) of deletions plus small insertions, symmetric elements for one-half of all antigen receptor-mediated translocations, while direct repeats appear only to be involved in mediating simple deletions. These findings extend our understanding of illegitimate recombination by highlighting the importance of secondary structure formation between single-stranded DNA ends at breakpoint junctions. Copyright 2003 Wiley-Liss, Inc.

  19. Impact of the AD 79 explosive eruption on Pompeii, II. Causes of death of the inhabitants inferred by stratigraphic analysis and areal distribution of the human casualties

    Science.gov (United States)

    Luongo, Giuseppe; Perrotta, Annamaria; Scarpati, Claudio; De Carolis, Ernesto; Patricelli, Giovanni; Ciarallo, Annamaria

    2003-08-01

    Detailed descriptions of the effects of explosive eruptions on urban settlements available to volcanologists are relatively rare. Apart from disease and starvation, the largest number of human deaths caused by explosive eruptions in the twentieth century are due to pyroclastic flows. The relationship between the number of victims related to a specific hazard and the presence of urban settlements in the area covered by the eruption has been shown. However, pyroclastic falls are also extremely dangerous under certain conditions. These conclusions are based on archaeological and volcanological studies carried out on the victims of the well-known AD 79 eruption of Vesuvius that destroyed and buried the Roman city of Pompeii. The stratigraphic level in the pyroclastic deposit and the location of all the casualties found are described and discussed. The total number of victims recovered during the archaeological excavations amounts to 1150. Of these, 1044 well recognisable bodies plus an additional group of 100 individuals were identified based on the analysis of several groups of scattered bones. Of the former, 394 were found in the lower pumice lapilli fall deposit and 650 in the upper stratified ash and pumice lapilli pyroclastic density currents (PDCs) deposits. In addition, a tentative evaluation suggests that 464 corpses may still be buried in the unexcavated part of the city. According to the reconstruction presented in this paper, during the first phase of the eruption (August 24, AD 79) a huge quantity of pumice lapilli fell on Pompeii burying the city under 3 m of pyroclastic material. During this eruptive phase, most of the inhabitants managed to leave the city. However, 38% of the known victims were killed during this phase mainly as a consequence of roofs and walls collapsing under the increasing weight of the pumice lapilli deposit. During the second phase of the eruption (August 25, AD 79) 49% of the total victims were on the roadways and 51% inside

  20. Effect of physical exertion on the biological monitoring of exposure to various solvents following exposure by inhalation in human volunteers: II. n-Hexane.

    Science.gov (United States)

    Tardif, Robert; Nadeau, Véronique; Truchon, Ginette; Brochu, Martin

    2007-07-01

    This study evaluated the impact of physical exertion on two n-hexane (HEX) exposure indicators in human volunteers exposed under controlled conditions in an inhalation chamber. A group of four volunteers (two women, two men) were exposed to HEX (50 ppm; 176 mg/m(3)) according to several scenarios involving several periods when volunteers performed either aerobic (AERO), muscular (MUSC), or both AERO/MUSC types of exercise. The target intensities for 30-min exercise periods separated by 15-min rest periods were the following: REST, 50W AERO [time-weighted average intensity including resting period (TWAI): 38W], 50W AERO/MUSC (TWAI: 34W), 100W AERO/MUSC (TWAI: 63W), and 100W AERO (TWAI: 71W) for 7 hr (two 3-hr exposure periods separated by 1 hr without exposure) and 50W MUSC for 3 hr (TWAI: 31W). Alveolar air and urine samples were collected at different time intervals before, during, and after exposure to measure unchanged HEX in expired air (HEX-A) and urinary 2,5-hexanedione (2,5-HD). HEX-A levels during exposures involving AERO activities (TWAI: 38W and 71W) were significantly enhanced (approximately +14%) compared with exposure at rest. MUSC or AERO/MUSC exercises were also associated with higher HEX-A levels but only at some sampling times. In contrast, end-of-exposure (7 hr) urinary 2,5-HD (mean +/- SD) was not modified by physical exertion: 4.14 +/- 1.51 micromol/L (REST), 4.02 +/- 1.52 micromol/L (TWAI 34W), 4.25 +/- 1.53 micromol/L (TWAI 38W), 3.73 +/- 2.09 micromol/L (TWAI 63W), 3.6 +/- 1.34 micromol/L (TWAI 71W) even though a downward trend was observed. Overall, this study showed that HEX kinetics is practically insensitive to moderate variations in workload intensity; only HEX-A levels increased slightly, and urinary 2,5-HD levels remained unchanged despite the fact that all types of physical exercise increased the pulmonary ventilation rate.

  1. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II ...

    Indian Academy of Sciences (India)

    Unknown

    Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N RAMAN*, Y PITCHAIKANI RAJA and A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001, India e-mail: ra_man@123india.com.

  2. Environmental Change in Post-closure Safety Assessment of Solid Radioactive Waste Repositories. Report of Working Group 3 Reference Models for Waste Disposal of EMRAS II Topical Heading Reference Approaches for Human Dose Assessment. Environmental Modelling for Radiation Safety (EMRAS II) Programme

    International Nuclear Information System (INIS)

    2016-08-01

    Environmental assessment models are used for evaluating the radiological impact of actual and potential releases of radionuclides to the environment. They are essential tools for use in the regulatory control of routine discharges to the environment and also in planning measures to be taken in the event of accidental releases. They are also used for predicting the impact of releases which may occur far into the future, for example, from underground radioactive waste repositories. It is important to verify, to the extent possible, the reliability of the predictions of such models by a comparison with measured values in the environment or with predictions of other models. The IAEA has been organizing programmes of international model testing since the 1980s. These programmes have contributed to a general improvement in models, in the transfer of data and in the capabilities of modellers in Member States. IAEA publications on this subject over the past three decades demonstrate the comprehensive nature of the programmes and record the associated advances which have been made. From 2009 to 2011, the IAEA organized a programme entitled Environmental Modelling for Radiation Safety (EMRAS II), which concentrated on the improvement of environmental transfer models and the development of reference approaches to estimate the radiological impacts on humans, as well as on flora and fauna, arising from radionuclides in the environment. Different aspects were addressed by nine working groups covering three themes: reference approaches for human dose assessment, reference approaches for biota dose assessment and approaches for assessing emergency situations. This publication describes the work of the Reference Models for Waste Disposal Working Group

  3. The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.

    Science.gov (United States)

    Romeo, Megan; Hutchison, Tetiana; Malu, Aditi; White, Averi; Kim, Janice; Gardner, Rachel; Smith, Katie; Nelson, Katherine; Bergeson, Rachel; McKee, Ryan; Harrod, Carolyn; Ratner, Lee; Lüscher, Bernhard; Martinez, Ernest; Harrod, Robert

    2018-05-01

    In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30 II , associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma cells with elevated c-Myc expression. Our results allude to a pivotal role for p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in viral and non-viral lymphoid tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

    Science.gov (United States)

    Overton, Edgar Turner; Stapleton, Jack; Frank, Ian; Hassler, Shawn; Goepfert, Paul A.; Barker, David; Wagner, Eva; von Krempelhuber, Alfred; Virgin, Garth; Meyer, Thomas Peter; Müller, Jutta; Bädeker, Nicole; Grünert, Robert; Young, Philip; Rösch, Siegfried; Maclennan, Jane; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2015-01-01

    Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID:26380340

  5. Organometallic DNA-B12 Conjugates as Potential Oligonucleotide Vectors: Synthesis and Structural and Binding Studies with Human Cobalamin-Transport Proteins.

    Science.gov (United States)

    Mutti, Elena; Hunger, Miriam; Fedosov, Sergey; Nexo, Ebba; Kräutler, Bernhard

    2017-11-16

    The synthesis and structural characterization of Co-(dN) 25 -Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN) 39 -Cbl, which are organometallic DNA-B 12 conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA-Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA-Cbls for the task of eventual in vivo oligonucleotide delivery. The binding of DNA-Cbl to TC, IF, and HC was investigated in competition with either a fluorescent Cbl derivative and Co-(dN) 25 -Cbl, or radiolabeled vitamin B 12 ( 57 Co-CNCbl) and Co-(dN) 25 -Cbl or Co-(dN) 39 -Cbl. Binding of the new DNA-Cbl conjugates was fast and tight with TC, but poorer with HC and IF, which extends a similar original finding with the simpler DNA-Cbl, Co-(dN) 18 -Cbl. The contrasting affinities of TC versus IF and HC for the DNA-Cbl conjugates are rationalized herein by a stepwise mechanism of Cbl binding. Critical contributions to overall affinity result from gradual conformational adaptations of the Cbl-binding proteins to the DNA-Cbl, which is first bound to the respective β domains. This transition is fast with TC, but slow with IF and HC, with which weaker binding results. The invariably tight interaction of the DNA-Cbl conjugates with TC makes the Cbl moiety a potential natural vector for the specific delivery of oligonucleotide loads from the blood into cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. U-14C-lactate-to-glycogen conversion and glycogen resynthesis rates in Type I and Type II human vastus lateralis muscle determined from biopsy samples following supramaximal and submaximal exhaustive one-leg cycling: an in vitro versus in vivo comparison

    International Nuclear Information System (INIS)

    Thompson, J.L.

    1987-01-01

    To determine the in vitro lactate-to-glycogen conversion potential of human muscle, samples were incubated in U- 14 C-lactate. Because evidence existed suggesting that lactate-to-glycogen conversion occurred at a faster rate in Type II muscle in vivo glycogen resynthesis was calculated by the difference in muscle glycogen concentrations over the initial half-hour recovery period in the FT (Type II, fast-twitch) and ST (Type I, slow-twitch) muscle fiber pools from two of the original eight subjects

  7. The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein.

    Science.gov (United States)

    Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S; Tosi, Giovanna

    2016-01-20

    Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the cytoplasm. Nuclear CIITA associates with Tax-1/RelA in nuclear bodies, blocking Tax-1-dependent activation of NF-κB-responsive genes. Thus, CIITA inhibits cytoplasmic and nuclear steps of Tax-1-mediated NF-κB activation. These results, together with our previous finding that CIITA acts as a restriction factor inhibiting Tax-1-promoted HTLV-1 gene expression and replication, indicate that CIITA is a versatile molecule that might also counteract Tax-1 transforming activity. Unveiling the molecular basis of CIITA-mediated inhibition of Tax-1 functions may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential. HTLV-1 is the causative agent of human adult T cell leukemia-lymphoma (ATLL). The viral

  8. Phase II Study of Paclitaxel Given Once per Week Along With Trastuzumab and Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

    Science.gov (United States)

    Dang, Chau; Iyengar, Neil; Datko, Farrah; D'Andrea, Gabriella; Theodoulou, Maria; Dickler, Maura; Goldfarb, Shari; Lake, Diana; Fasano, Julie; Fornier, Monica; Gilewski, Theresa; Modi, Shanu; Gajria, Devika; Moynahan, Mary Ellen; Hamilton, Nicola; Patil, Sujata; Jochelson, Maxine; Norton, Larry; Baselga, Jose; Hudis, Clifford

    2015-01-01

    Purpose The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week. Patients and Methods Patients with metastatic human epidermal growth factor receptor 2–positive breast cancer with zero to one prior therapy were enrolled. Treatment consisted of paclitaxel 80 mg/m2 once per week plus trastuzumab (8 mg/kg loading dose → 6 mg/kg) once every 3 weeks plus pertuzumab (840 mg loading dose → 420 mg) once every 3 weeks, all given intravenously. The primary end point was 6-month PFS assessed by Kaplan-Meier methods. Results From January 2011 to December 2013, we enrolled 69 patients: 51 (74%) and 18 (26%) treated in first- and second-line metastatic settings, respectively. At a median follow-up of 21 months (range, 3 to 38 months), 6-month PFS was 86% (95% CI, 75% to 92%). The median PFS was 19.5 months (95% CI, 14 to 26 months) overall. PFS was 24.2 months (95% CI, 14 months to not reached [NR]) and 16.4 months (95% CI, 8.5 months to NR) for those without and with prior treatment, respectively. At 1 year, Kaplan-Meier PFS was 70% (95% CI, 56% to 79%) overall, 71% (95% CI, 55% to 82%) for those without prior therapy, and 66% (95% CI, 40% to 83%) for those with prior therapy. Treatment was well-tolerated; there was no febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusion Paclitaxel given once per week with trastuzumab and pertuzumab is highly active and well tolerated and seems to be an effective alternative to docetaxel-based combination therapy. PMID:25547504

  9. Reclassification of the Candida haemulonii Complex as Candida haemulonii (C. haemulonii Group I), C. duobushaemulonii sp. nov. (C. haemulonii Group II), and C. haemulonii var. vulnera var. nov.: Three Multiresistant Human Pathogenic Yeasts

    NARCIS (Netherlands)

    Cendejas-Bueno, E.; Kolecka, A.; Alastruey-Izquierdo, A.; Theelen, B.; Groenewald, M.; Kostrzewa, M.; Cuenca-Estrella, M.; Gomez-Lopez, A.; Boekhout, T.

    2012-01-01

    The Candida haemulonii species complex is currently known as C. haemulonii groups I and II. Here we describe C. haemulonii group II as a new species, Candida duobushaemulonii sp. nov., and C. haemulonii var. vulnera as new a variety of C. haemulonii group I using phenotypic and molecular methods.

  10. Antimicrobial Exposure Assessment Task Force II (AEATF II) Volume 5: Governing Document for a Multi-Year Antimicrobial Chemical Exposure Monitoring Program (interim draft document with changes)

    Science.gov (United States)

    This document describes the overall scope of the AEATF II program, demonstrates the need for additional human exposure monitoring data and explains the proposed methodology for the exposure monitoring studies proposed for conduct by the AEATF II.

  11. Antimicrobial Exposure Assessment Task Force II (AEATF II) Volume 5: Governing Document for a Multi-Year Antimicrobial Chemical Exposure Monitoring Program (interim draft document)

    Science.gov (United States)

    Describes the overall scope of the AEATF II program, demonstrates the need for additional human exposure monitoring data and explains the proposed methodology for the exposure monitoring studies proposed for conduct by the AEATF II.

  12. (II) COMPLEX COMPOUND

    African Journals Online (AJOL)

    user

    electrochemical sensors, as well as in various chromatographic ... were carried out using Jenway pH meter Model 3320 and a conductivity ... Figure 1: the proposed molecular structure of the copper (II) Schiff base complex. M = Cu (II) or Mn (II).

  13. and copper(II)

    Indian Academy of Sciences (India)

    Unknown

    (II) and copper(II)–zinc(II) complexes. SUBODH KUMAR1, R N PATEL1*, P V KHADIKAR1 and. K B PANDEYA2. 1 Department of Chemistry, APS University, Rewa 486 003, India. 2 CSJM University, Kanpur 208 016, India e-mail: (R N Patel) ...

  14. Testing the Gossamer Albatross II

    Science.gov (United States)

    1980-01-01

    The Gossamer Albatross II is seen here during a test flight at NASA's Dryden Flight Research Center, Edwards, California. The original Gossamer Albatross is best known for completing the first completely human powered flight across the English Channel on June 12, 1979. The Albatross II was the backup craft for the Channel flight. It was fitted with a small battery-powered electric motor and flight instruments for the NASA research program in low-speed flight. NASA completed its flight testing of the Gossamer Albatross II and began analysis of the results in April, 1980. During the six week program, 17 actual data gathering flights and 10 other flights were flown here as part of the joint NASA Langley/Dryden flight research program. The lightweight craft, carrying a miniaturized instrumentation system, was flown in three configurations; using human power, with a small electric motor, and towed with the propeller removed. Results from the program contributed to data on the unusual aerodynamic, performance, stability, and control characteristics of large, lightweight aircraft that fly at slow speeds for application to future high altitude aircraft. The Albatross' design and research data contributed to numerous later high altitude projects, including the Pathfinder.

  15. Pius II. a utrakvismus

    OpenAIRE

    Šimek, Milan

    2009-01-01

    Milan Šimek Pius II. a utrakvismus Pius II. and utraquism Based on sources work - out, the thesis aims the description and analysis of the attitude alternation of Enea Sylvio Piccolomini - Pius II to the utraquism. The conclusions stress the postulate that Pius II. did not change that attitude, but just did not succed in quelling the utraquist movement. In the sense of political background that finally led to fatal dissention among both leaders, king Jiří of Poděbrady and pope Pius II.

  16. Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

    Science.gov (United States)

    El-Boraey, Hanaa A.

    2012-11-01

    Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.

  17. Sex differences in angiotensin II- induced hypertension

    Directory of Open Access Journals (Sweden)

    B. Xue

    2007-05-01

    Full Text Available Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

  18. Complexes of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and dioxouranium(II) with thiophene-2-aldehydethiosemicarbazone

    International Nuclear Information System (INIS)

    Singh, Balwan; Misra, Harihar

    1986-01-01

    Metal complexes of thiosemicarbazides have been known for their pharmacological applications. Significant antitubercular, fungicidal and antiviral activities have been reported for thiosemicarbazides and their derivatives. The present study describes the systhesis and characterisation of complexes of Co II , Cu II , Zn II ,Cd II and UO II with thiosemicarbazone obtained by condensing thiophene-2-aldehyde with thiosemicarbazide. 17 refs., 2 tables. (author)

  19. Textos sobre Sostenibilidad II

    Directory of Open Access Journals (Sweden)

    Ciudades para un futuro más sostenible http://habitat.aq.upm.es

    2004-12-01

    This issue assembles a selection of articles publicly available on the website Ciudades para un Futuro más Sostenible (CF+S: http://habitat.aq.upm.es. This selection was originally used as a printed companion guide to the public lecture series on ‘‘Sustainability in the Architecture and Urban Project’’, held on March 2004 and organized by the Madrid School of Architecture within the Initiative for a more Sustainable Architecture and Urbanism (IAU+S. The compilation an overall vision on sustainability presents to average audience. The basic criterion to select these articles was therefore a pedagogical one, including those simpler and clearer papers dealing with all main topics in CF+S. However, due to space limitations, many excellent articles available on the website are unfortunately not included within this selection. CF+S was created in 1996 as a partnership between the Spanish Ministry of Works and Madrid School of Architecture. The objective was to translate into Spanish and publish the experiences selected at the International Award for Best Practices in Improving the Living Environment, organized by United Nations after the Istanbul Conference on Human Settlements (Habitat II. CF+S aims to gather documents concerning any kind of actions and experiences both on the territory and the city actually improving people’s living conditions according to the sustainability concept in its strongest sense. It also offers papers, reports and theoretical reflections on the state of and the possible alternatives to urban development nowadays.

  20. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

    Science.gov (United States)

    Gelman, Rebecca S.; Wefel, Jeffrey S.; Melisko, Michelle E.; Hess, Kenneth R.; Connolly, Roisin M.; Van Poznak, Catherine H.; Niravath, Polly A.; Puhalla, Shannon L.; Ibrahim, Nuhad; Blackwell, Kimberly L.; Moy, Beverly; Herold, Christina; Liu, Minetta C.; Lowe, Alarice; Agar, Nathalie Y.R.; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F.; Krop, Ian E.; Wolff, Antonio C.; Winer, Eric P.; Lin, Nancy U.

    2016-01-01

    Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies