WorldWideScience

Sample records for infected cell half-life

  1. Intrinsically Disordered Segments Affect Protein Half-Life in the Cell and during Evolution

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2014-09-01

    Full Text Available Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

  2. Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells.

    Science.gov (United States)

    Di Scala, Coralie; Mazzarino, Morgane; Yahi, Nouara; Varini, Karine; Garmy, Nicolas; Fantini, Jacques; Chahinian, Henri

    2017-06-01

    Anandamide (AEA) is a ubiquitous lipid that exerts neurotransmitter functions but also controls important biological functions such as proliferation, survival, or programmed cell death. The latter effects are also regulated by ceramide, a lipid enzymatically generated from sphingomyelin hydrolysis by sphingomyelinase. Ceramide has been shown to increase the cellular toxicity of AEA, but the mechanisms controlling this potentiating effect remained unclear. Here we have used a panel of in silico, physicochemical, biochemical and cellular approaches to study the crosstalk between AEA and ceramide apoptotic pathways. Molecular dynamics simulations indicated that AEA and ceramide could form a stable complex in phosphatidylcholine membranes. Consistent with these data, we showed that AEA can specifically insert into ceramide monolayers whereas it did not penetrate into sphingomyelin membranes. Then we have studied the effects of ceramide on AEA-induced toxicity of human neuroblastoma cells. In these experiments, the cells have been either naturally enriched in ceramide by neutral sphingomyelinase pre-incubation or treated with C2-ceramide, a biologically active ceramide analog. Both treatments significantly increased the cytotoxicity of AEA as assessed by the MTS mitochondrial toxicity assay. This effect was correlated with the concomitant accumulation of natural ceramide (or its synthetic analog) and AEA in the cells. A kinetic study of AEA hydrolysis showed that ceramide inhibited the fatty acid amino hydrolase (FAAH) activity in cell extracts. Taken together, these data suggested that ceramide binds to AEA, increases its half-life and potentiates its cytotoxicity. Overall, these mechanisms account for a functional cross-talk between AEA and ceramide apoptotic pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Phenytoin shortens the half-life of the hypoxic cell radiosensitizer misonidazole in man: implications for possible reduced toxicity

    International Nuclear Information System (INIS)

    Workman, P.; Bleehen, N.M.; Wiltshire, C.R.; Cambridge Univ.

    1980-01-01

    Results are described of a preliminary study of the effects of phenytoin, (commonly used as an anticonvulsant in the treatment of patients with brain tumours), on the plasma pharmacokinetics of misonidazole (MISO) in man. Previous studies have shown that pretreatment with phenytoin shortens the half-life of MISO in dogs and mice by induction of drug metabolizing enzymes, and also reduces the acute lethal effects of MISO in mice. In this study patients with various types of malignancy and with cerebral metastases were given MISO before and after a course of phenytoin. Others were assessed as controls without phenytoin administration. Plasma concentrations of MISO were determined in blood samples taken before and at various times after administration. A summary of the pharmacokinetic data obtained is given. (author)

  4. Half-life of 230Th

    International Nuclear Information System (INIS)

    Meadows, J.W.; Armani, R.J.; Callis, E.L.; Essling, A.M.

    1980-01-01

    The half-life of 230 Th was measured by the specific activity method. Alpha counting was done in a low geometry counter whose geometry factor was calculated from its dimensions. Sample weights were determined by isotopic dilution. Measurements were made on four isotopic mixtures ranging from 0.383 to 99.52% 230 Th. The half-life is 75381 +- 295 years

  5. Half-life measurement of 89Rb

    International Nuclear Information System (INIS)

    Guo Xiaoqing; Yuan Daqing; Xu Lijun; Chen Kesheng; Wu Yongle; Zheng Yanming; Yao Shunhe

    2013-01-01

    89 Rb is an important fission product used for monitoring possible release of fission products from fuel element. The half-life is one of important nuclear parameters. The half-life of 89 Rb was determined using reference source method with two sets of HPGe detectors by place-relay way. In reference source method, the ratio of net full- energy peak areas from the measure nuclide and the reference source was used to avoid the count correction caused by dead time and pileup. For the very short half-life of 89 Rb, the half-life iterative method was used in data analysis and the translation method was used in data unification. Finally, the measured half-life of 89 Rb is (14.41±0.04) min. (authors)

  6. Real-time RT-PCR analysis of mRNA decay: half-life of Beta-actin mRNA in human leukemia CCRF-CEM and Nalm-6 cell lines

    Directory of Open Access Journals (Sweden)

    Barredo Julio C

    2002-03-01

    Full Text Available Abstract Background We describe an alternative method to determine mRNA half-life (t1/2 based on the Real-Time RT-PCR procedure. This approach was evaluated by using the β-actin gene as a reference molecule for measuring of mRNA stability. Results Human leukemia Nalm-6 and CCRF-CEM cells were treated with various concentrations of Actinomycin D to block transcription and aliquots were removed periodically. Total RNA was isolated and quantified using the RiboGreen® fluorescent dye with the VersaFluor Fluorometer System. One μg of total RNA was reverse transcribed and used as template for the amplification of a region of the β-actin gene (231 bp. To generate the standard curve, serial ten-fold dilutions of the pBactin-231 vector containing the cDNA amplified fragment were employed, β-actin mRNAs were quantified by Real-Time RT-PCR using the SYBR® Green I fluorogenic dye and data analyzed using the iCycle iQ system software. Using this method, the β-actin mRNA exhibited a half-life of 6.6 h and 13.5 h in Nalm-6 and CCRF-CEM cells, respectively. The t1/2 value obtained for Nalm-6 is comparable to those estimated from Northern blot studies, using normal human leukocytes (5.5 h. Conclusions We have developed a rapid, sensitive, and reliable method based on Real-Time RT-PCR for measuring mRNA half-life. Our results confirm that β-actin mRNA half-life can be affected by the cellular growth rate.

  7. Half-life determination of 125I

    International Nuclear Information System (INIS)

    De Felice, P.; Ientile, P.; Zicari, C.

    1990-01-01

    The half-life of 125 I was determined by measuring the activity of an initial 3 kBq source at several times. Over a period of two months, 96 absolute measurements were performed, using the sum-peak method to give a half-life of (59.38±0.03) d. A discussion is presented on the effect of correcting for accidental coincidences on the half-life measurements by comparing the results with and without this correction. (orig.)

  8. Half Life Measurements in 155Gd

    International Nuclear Information System (INIS)

    Malmskog, S.G.

    1966-08-01

    In the literature there exists a definite difference for the half life of the 86.5 keV level in Gd depending on whether 155 Eu or 155 Tb sources have been used. Using a good energy resolution electron-electron coincidence spectrometer and a 155 Eu source, a half life of 6.48 ± 0.26 nsec was obtained for the 86.5 keV level. This is in agreement with the values previously measured with 155 Tb sources. The half life of the 105.4 keV level was measured to be 1.12 ± 0.05 nsec

  9. Half Life Measurements in {sup 155}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S G

    1966-08-15

    In the literature there exists a definite difference for the half life of the 86.5 keV level in Gd depending on whether {sup 155}Eu or {sup 155}Tb sources have been used. Using a good energy resolution electron-electron coincidence spectrometer and a {sup 155}Eu source, a half life of 6.48 {+-} 0.26 nsec was obtained for the 86.5 keV level. This is in agreement with the values previously measured with {sup 155}Tb sources. The half life of the 105.4 keV level was measured to be 1.12 {+-} 0.05 nsec.

  10. 243Cm half-life determinaton

    International Nuclear Information System (INIS)

    Timofeev, G.A.; Kalygin, V.V.; Privalova, P.A.

    1986-01-01

    By molar ratios of 243 Cm mixture with 244 Cm and Pu nuclides formed as a result of Cm nuclides α-decay the 243 Cm half-life T α243 is determined. The 244 Cm half-life is measured earlier with high accuracy. The 243 Cm/ 244 Cm ratio measured by means of a mass spectrometer equals 0.989+-0.004. The obtained value T α243 =29.20+-0.14 years

  11. Half-life determination for 27Mg

    Science.gov (United States)

    Zahn, G. S.; Genezini, F. A.

    2015-07-01

    In this work, the half-life of the short-lived magnesium radionuclide 27Mg was measured by following the activity of samples after they were irradiated in the IEA-R1 reactor. An exponential decay function was then fitted to the results using the counts from a 60Co source as livetime chronometer; the individual half-life values obtained for each irradiation were compiled using both the usual unweighted and σ-2-weighted averages, as well as the robust averages obtained using the Normalized Residuals and the Rajeval techniques. The final halflive values obtained aren't compatible with the ENSDF compilation values, but have a similar uncertainty; analysis of the experimental literature values, all from the 50’s-60’s, show that further measurements should be undertaken in order to achieve a more robust consensus value for this half-life.

  12. Half-life of 51Mn

    Science.gov (United States)

    Graves, Stephen A.; Ellison, Paul A.; Valdovinos, Hector F.; Barnhart, Todd E.; Nickles, Robert J.; Engle, Jonathan W.

    2017-07-01

    The half-life of 51Mn was measured by serial gamma spectrometry of the 511-keV annihilation photon following decay by β+ emission. Data were collected every 100 seconds for 100,000-230,000 seconds within each measurement (n =4 ). The 511-keV incidence rate was calculated from the 511-keV spectral peak area and count duration, corrected for detector dead time and radioactive decay. Least-squares regression analysis was used to determine the half-life of 51Mn while accounting for the presence of background contaminants, notably 55Co. The result was 45.59 ±0.07 min, which is the highest precision measurement to date and disagrees with the current Nuclear Data Sheets value by over 6 σ .

  13. Half-life of samarium-147

    CERN Document Server

    Kinoshita, N; Nakanishi, T

    2003-01-01

    The alpha-decay half-life of sup 1 sup 4 sup 7 Sm has been reevaluated. Known amounts of natural Sm and an alpha-emitter standard ( sup 2 sup 1 sup 0 Po, sup 2 sup 3 sup 8 U, or sup 2 sup 4 sup 1 Am) were mixed well to prepare thin sources for the simultaneous counting of sup 1 sup 4 sup 7 Sm and the alpha-emitter standard by means of an alpha-spectrometer using a silicon surface barrier detector. The alpha-disintegration rate of known amounts of sup 1 sup 4 sup 7 Sm was determined by reference to the alpha activity of the standard. The source preparation and counting were repeated to establish the reproducibility of the present half-life determination, and supplementary alpha spectrometry was carried out by a liquid-scintillation spectrometer. The arithmetic mean of the experimental half-life values was obtained to be (1.17 +- 0.02) x 10 sup 1 sup 1 y. This value is about 10% longer than the currently adopted value, (1.06 +- 0.02) x 10 sup 1 sup 1 y, and the possible factors for this difference are discussed...

  14. The half-life of 125I

    International Nuclear Information System (INIS)

    Simpson, B.R.S.; Meyer, B.R.

    1989-01-01

    The Bureau International des Poids et Mesures (BIPM) organized an international comparison of activity measurements of a solution of 125 I. The half-life value adopted was 59.5±0.4d. The large uncertainty took account of a recently published value (Schrader, 1986) which is considerably lower than the widely used value of 60.0±0.1d. The present work, which was undertaken at the suggestion of the BIPM, has yielded a value which confirms the lower measurement. (author)

  15. Half-life of Xe120

    Science.gov (United States)

    Phillips, A. A.; Andreoiu, C.; Ball, G. C.; Bandyopadhyay, D.; Behr, J. A.; Chupp, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hayden, M. E.; Hyland, B.; Nuss-Warren, S. R.; Pearson, M. R.; Schumaker, M. A.; Smith, M. B.; Svensson, C. E.; Tardiff, E. R.; Valiente-Dobón, J. J.; Warner, T.

    2006-08-01

    We have measured the half-life of Xe120 using a high-purity germanium (HPGe) detector to monitor the 176, 178, and 762 keV γ rays from Xe120 β+ decay. The result, 46±0.6 min, differs significantly from the value 40±1 min reported by Andersson [Ark. Fys. 28, 37 (1964)]. We have also measured the half-lives of Cs120 and I120 to be 60±0.7 s and 82.1±0.6 min, respectively, both of which are consistent with previous measurements.

  16. Immunological half-life of porcine proinsulin C-peptide

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, H; Horino, M; Matsumura, S [Kawasaki Medical Coll., Kurashiki (Japan). Div. of Endocrinology; Kobayshi, K; Suetsugu, N [Yamaguchi Univ., Ube (Japan). School of Medicine

    1975-11-01

    Immunological half-lifes of injected porcine C-peptide and insulin with RIA were studied and calculated as 9.8 and 8.0 minutes. Higher circulating levels of C-peptide as compared to insulin in normal young swines lead to speculation about a longer half-life of C-peptide. This hypothesis was verified in this study. Immunological half-lifes of porcine proinsulin and insulin in the pig were 20 and 6 minutes, respectively.

  17. Experimental study of half-life determinations using 60Co

    International Nuclear Information System (INIS)

    Rutledge, A.R.; Smith, L.V.; Merritt, J.S.

    1983-01-01

    The half-life of 60 Co was determined by two methods, (i) the 4π#betta# ionization chamber method and (ii) the 4π #betta#-#betta# coincidence method. The first is a relative counting method in which the only rate-dependent correction is for background, whereas the second is an 'absolute' counting method which involves several rate-dependent corrections. In addition, various methods of calculation of the results were tested. The half-life values for the two counting systems were in good agreement and the weighted mean value for the half-life of 60 Co was found to be 1925.02+-0.47 d. (orig.)

  18. Designing of peptides with desired half-life in intestine-like environment

    KAUST Repository

    Sharma, Arun

    2014-08-20

    Background: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti-hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life.Results: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides.Conclusion: In summary, this study describes a web server \\'HLP\\' that has been developed for assisting scientific

  19. A new determination of the 209Po half-life

    International Nuclear Information System (INIS)

    Collé, R; Fitzgerald, R P; Laureano–Perez, L

    2014-01-01

    A substantial 25% error in the then-known and accepted (102 ± 5) year half-life of 209 Po was reported on in 2007. This error was detected from decay data from two separate primary standardizations of a 209 Po solution standard, which were performed approximately 12 years apart. Despite author claims that this observation was not a new half-life determination, it was nevertheless included in subsequent nuclear data evaluations and compilations to obtain a currently tabulated value of (115 ± 13) a, computed from the median and range of the two half-life reports. A third primary standardization on the identical 209 Po solution has since been performed to derive a new half-life value of (125.2 ± 3.3) a. This half-life determination was obtained from 30 distinct data sets over a period of 20.7 years, encompassing over 700 liquid scintillation measurements with nearly 50 counting sources all prepared from the same solution, and as obtained over a very broad range of measurement conditions (composition of cocktails, characteristics of counters, time sequencing) during five periods in 1993, 1994, 2005, and 2013. (paper)

  20. Half-life of 90Sr - measurement and critical review

    International Nuclear Information System (INIS)

    Woods, M.J.; Lucas, S.E.M.

    1996-01-01

    Recent evaluations of the half-life of 90 Sr have demonstrated the variable quality of the available experimental data which has prevented the estimation and adoption of a value that commands confidence. In an attempt to reduce the uncertainty in the half-life to an acceptable level, the decay of a 90 Sr source has been followed for over six years at NPL. The equipment comprised matching, re-entrant, high-pressure ionization chambers and a long-lived reference source to reduce non-random effects. The experimental technique is described together with the statistical procedure used to analyse the measured data. A half-life value was determined together with an estimate of the associated uncertainties. A new evaluation of the 90 Sr half-life has been made, taking account of the new NPL data and other recent measurements. Particular attention has been paid to the experimental techniques used to produce the data and the uncertainties attributed to them. An objective evaluation has been conducted to produce a new recommended half-life value of 10 516 ± 21 days. (orig.)

  1. The Half-Life of the HSV-1 1.5 kb LAT Intron is similar to the half-Life of the 2.0 kb LAT Intron

    Science.gov (United States)

    Brinkman, Kerry K.; Mishra, Prakhar; Fraser, Nigel W.

    2013-01-01

    Herpes Simplex Virus type 1 (HSV-1) establishes a latent infection in the sensory neurons of the peripheral nervous system of humans. Although about 80 genes are expressed during the lytic cycle of the virus infection, essentially only one gene is expressed during the latent cycle. This gene is known as the latency associated transcript (LAT) and it appears to play a role in the latency cycle through an anti-apoptotic function in the 5’ end of the gene and miRNA encoded along the length of the transcript which down regulate some of the viral immediate early (IE) gene products. The LAT gene is about 8.3 kb long and consists of two exons separated by an unusual intron. The intron between the exons consists of two nested introns. This arrangement of introns has been called a twintron. Furthermore, the larger (2 kb) intron has been shown to be very stable. In this study we measure the stability of the shorter 1.5 kb nested intron and find its half-life is similar to the longer intron. This was achieved by deleting the 0.5 kb overlapping intron from a plasmid construct designed to express the LAT transcript from a tet-inducible promoter, and measuring the half-life of the 1.5 kb intron in tissue culture cells. This finding supports the hypothesis that it is the common branch-point region of these nested introns that is responsible for their stability. PMID:23335177

  2. Determination of the {sup 151}Sm half-life

    Energy Technology Data Exchange (ETDEWEB)

    Be, Marie-Martine; Cassette, Philippe [CEA, LIST, Gif sur Yvette (France). LNE-Laboratoire National Henri Becquerel; Isnard, Helene [CEA-LANIE, Gif sur Yvette (France); and others

    2015-07-01

    New measurements have been undertaken to determine the half-life of {sup 151}Sm. A pure {sup 151}Sm solution was obtained after chemical separation from a samarium solution resulting from the dissolution of an irradiated samarium sample. The concentration of {sup 151}Sm in the solution was measured by mass spectrometry, combined with the isotope dilution technique. The activity of the solution was measured by liquid scintillation counting by six European laboratories as part of an international comparison. These combined results lead to a half-life of T{sub 1/2} = 94.6(6)a.

  3. Calculation of the biological half-life of radioactive isotopes

    International Nuclear Information System (INIS)

    Szabo, S.A.

    1982-01-01

    The biological half-life of 137 Cs and 90 Sr was determined based on K and Ca metabolism and on the considerable chemical similarity of K and Ca, carriers of Cs and Sr, resp. The tsub(1/2)=a/bxln2 formula was used for the calculation, where a is the quantity of the element in question, while b is the daily need of the animal for the given element. The biological half-life for cattle of both 137 Cs and 90 Sr was found to be 30 days, while that for swine 20 days and 35 days respectively. (Sz.J.)

  4. Measurement of the 20F half-life

    Science.gov (United States)

    Hughes, M.; George, E. A.; Naviliat-Cuncic, O.; Voytas, P. A.; Chandavar, S.; Gade, A.; Huyan, X.; Liddick, S. N.; Minamisono, K.; Paulauskas, S. V.; Weisshaar, D.

    2018-05-01

    The half-life of the 20F ground state was measured using a radioactive beam implanted in a plastic scintillator and recording β γ coincidences together with four CsI(Na) detectors. The result, T1 /2=11.0011 (69) stat(30) sys s, is at variance by 17 combined standard deviations with the two most precise results. The present value revives the poor consistency of results for this half-life and calls for a new measurement, with a technique having different sources of systematic effects, to clarify the discrepancy.

  5. Half-life distribution table of radioactive nuclei

    International Nuclear Information System (INIS)

    Gugenberger, P.

    1954-01-01

    This table allows to identify an element if its period is known. Data for this table were taken from the half-life values adopted by Hollander, PERLMAN and SEABORG (Rev. mod. Phys., 1953, 22 number 2). Moreover for each nucleus, the mass number, the charge number and the type of decay are given in the table. (author) [fr

  6. Determination of disintegration half-life of 252Cf

    International Nuclear Information System (INIS)

    Chen Keliang; Liu Guoxing; Wang Sufang; Zheng Jiwen

    1991-01-01

    The follow-up measurements have been made by using a Si(Au) detector with small solid angle geometry for α disintegration of 252 Cf. The measured half-life of disintegration is 2.638 ± 0.009 year. This value is in accordance with other previous results

  7. Experimental half-life determination of 176Lu

    International Nuclear Information System (INIS)

    Kossert, Karsten; Jörg, Gerhard; Gostomski, Christoph Lierse v.

    2013-01-01

    The half-life of the naturally occurring long-lived rare earth isotope 176 Lu was determined by a combination of highly sophisticated experimental procedures in order to further improve the reliability and the precision of literature data. The amount of lutetium in the samples was determined by inductively coupled plasma optical emission spectrometry (ICP-OES) using a NIST reference standard. The isotopic ratio N( 176 Lu)/N(Lu) in the samples was measured by means of inductively coupled plasma high resolution mass spectrometry (ICP-HRMS). The activity divided by the mass of Lu was determined by applying liquid scintillation (LS) counting. The LS counting efficiency of the beta/gamma emitter 176 Lu was determined with the CIEMAT/NIST efficiency tracing technique with low uncertainty. The influences of colour quenching and background effects are discussed in this paper. The half-life was found to be 3.640(35)×10 10 y. The result is in good agreement with other evaluations and the relative standard uncertainty of 0.95% is among the lowest of previously published data. - Highlights: • The half-life of 176 Lu was determined by ICP-OES, ICP-HRMS and LSC. • The LSC efficiency was determined with the CIEMAT/NIST method. • The half-life was found to be 3.640(35)×10 10 y

  8. Beyond effective half-life characterization of radionuclide dynamics

    International Nuclear Information System (INIS)

    Hermanska, J.; Blazek, T.; Karny, M.

    1996-01-01

    A refined model was set up and tested of the effective radionuclide half-life in nuclear medicine, making allowance for the fact that the basic assumption that the observed data can be fitted by a mono-exponential, as well as some other assumptions, is not true. The results are discussed. (P.A.). 1 tab., 32 refs

  9. Half-life of the superallowed β+ emitter Ne18

    Science.gov (United States)

    Grinyer, G. F.; Smith, M. B.; Andreoiu, C.; Andreyev, A. N.; Ball, G. C.; Bricault, P.; Chakrawarthy, R. S.; Daoud, J. J.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Valiente-Dobón, J. J.; Williams, S. J.; Zganjar, E. F.

    2007-08-01

    The half-life of Ne18 has been determined by detecting 1042-keV γ rays in the daughter F18 following the superallowed-Fermi β+ decay of samples implanted at the center of the 8πγ-ray spectrometer, a spherical array of 20 HPGe detectors. Radioactive Ne18 beams were produced on-line, mass-separated, and ionized using an electron-cyclotron-resonance ionization source at the ISAC facility at TRIUMF in Vancouver, Canada. This is the first high-precision half-life measurement of a superallowed Fermi β decay to utilize both a large-scale HPGe spectrometer and the isotope separation on-line technique. The half-life of Ne18, 1.6656 ± 0.0019 s, deduced following a 1.4σ correction for detector pulse pile-up, is four times more precise than the previous world average. As part of an investigation into potential systematic effects, the half-life of the heavier isotope Ne23 was determined to be 37.11 ± 0.06 s, a factor of 2 improvement over the previous precision.

  10. Measurement of the 8Li half-life

    International Nuclear Information System (INIS)

    Flechard, X.; Lienard, E.; Naviliat-Cuncic, O.; Ban, G.; Carniol, B.; Etasse, D.; Fontbonne, J. M.; Rodriguez, D.; Lallena, A. M.; Alvarez, M. A. G.; Praena, J.

    2010-01-01

    We report a new measurement of the 8 Li half-life using a plastic scintillator and an ultrafast waveform digitizing module. The result, T 1/2 =(838.40±0.36) ms, improves by a factor of 2.5 the most precise result obtained so far and is furthermore deduced with negligible corrections due to dead time.

  11. Radioactive source simulation for half-life experiment

    International Nuclear Information System (INIS)

    Wanitsuksombut, Warapon; Decthyothin, Chanti

    1999-01-01

    A simulation of radioactivity decay by using programmable light source with a few minutes half-life is suggested. A photodiode with digital meter label in cps is use instead of radiation detector. Both light source and photodiode are installed in a black box to avoid surrounding room light. The simulation set can also demonstrate Inverse Square Law experiment of radiation penetration. (author)

  12. Measurement of the 230U half-life

    International Nuclear Information System (INIS)

    Pommé, S.; Altzitzoglou, T.; Van Ammel, R.; Suliman, G.; Marouli, M.; Jobbágy, V.; Paepen, J.; Stroh, H.; Apostolidis, C.; Abbas, K.; Morgenstern, A.

    2012-01-01

    The 230 U half-life was determined by measuring the decay curve of 230 U sources by various nuclear detection techniques: α-particle counting at a defined small solid angle; 4πα+β counting with a windowless CsI sandwich spectrometer, a liquid scintillation counter and a pressurised proportional counter; gamma-ray spectrometry with a HPGe detector and nearly-2π α-particle counting with an ion-implanted silicon detector. Depending on the technique, the decay was followed for 100–200 d, which is 5–10 times the 230 U half-life. The measurement results of the various techniques were in good mutual agreement. The mean value, T 1/2 ( 230 U)=20.23 (2) d, is lower than the literature value which is based on one measurement in 1948 and resulted in a half-life value of 20.8 d without statement of uncertainty. A correction for the ingrowth of the long-lived 210 Pb and its daughter products may have been overlooked in the past. - Highlights: ► Half-life of 230 U determined by various nuclear detection techniques. ► Result T 1/2 ( 230 U)=20.23 (2) d is lower than the literature value. ► 230 U/ 226 Th decay series has potential use in alpha-immunotherapy.

  13. Measurement of the half-life of 68Ga

    International Nuclear Information System (INIS)

    García-Toraño, Eduardo; Peyrés Medina, Virginia; Romero, Eduardo; Roteta, Miguel

    2014-01-01

    The half-life of the positron-emitter 68 Ga has been measured by following the decay rate with two systems based on ionization chamber and Ge detectors. The decay rate was measured for periods of time up to 10 half-lives. The combination of the 6 results obtained with both systems gives a value of T 1/2 =67.845(18) min, in good agreement with recommended data and with an uncertainty lower than any other previously reported value. - Highlights: • The half-life of the positron-emitter radionuclide 68 Ga was measured. • Two measurement setups (ionization chamber and Ge detector) were used. • Results agree with evaluated data but exhibit lower uncertainty

  14. Superior serum half life of albumin tagged TNF ligands

    International Nuclear Information System (INIS)

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-01-01

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  15. Half-life predictions for decay modes of superheavy nuclei

    International Nuclear Information System (INIS)

    Duarte, S.B.; Tavares, O.A.P.; Goncalves, M.; Rodriguez, O.; Guzman, F.; Barbosa, T.N.; Garcia, F.; Dimarco, A.

    2004-09-01

    We applied the Effective Liquid Drop Model (ELDM) to predict the alpha-decay, cluster emission and cold fission half-life-values of nuclei in the region of Superheavy Elements (SHE). The present calculations have been made in the region of the ZN-plane defined by 155 <=N <=220 and 110<=Z<=135. Shell effects are included via the Q-value of the corresponding decay case. We report the results of a systematic calculation of the half-life for the three nuclear decay modes in a region of the ZN-plane where superheavy elements are expected to be found. Results have shown that, among the decay modes investigated here, the alpha decay is the dominant one. i.e, the decay mode of smallest half-lives. Half-life predictions for alpha decay, cluster emission and cold fission for the isotopic family of the most recent SHE detected of Z=115 and for the isotopic family of the already consolidated SHE of Z=111 are presented. (author)

  16. Beryllium-10: Half-life and AMS-standards

    International Nuclear Information System (INIS)

    Hofmann, H.J.; Beer, J.; Bonani, G.; von Gunten, H.R.; Raman, S.; Suter, M.; Walker, R.L.; Woelfli, W.; Zimmermann, D.

    1987-01-01

    Absolute AMS measurements of 10 Be require reliable standards for calibration. Among the existing standards, rather large differences have been observed. These differences were found partially to be due to the different half-life values which were assumed. Also for comparison of AMS data with activity measurements, it is necessary to know the 10 Be half-life as precisely as possible. Starting with 5 ml of the standardized ORNL-MASTER solution, a working solution with a well-defined 10 Be content was prepared. Its specific activity was determined by liquid scintillation counting. This measurement yielded a new value of (1.52 +- 0.05) My for the 10 Be half-life, which is in agreement with the previously reported values but is about three times more accurate. Two independent dilution series produced new AMS standards with 10 Be/ 9 Be ratios of the order of 10 -10 and 10 -11 . These standards were measured at the ETH/SIN AMS facility with high accuracy and are compared with other available 10 Be standards. 15 refs, 2 figs., 3 tabs

  17. Precision half-life measurement of 17F

    Science.gov (United States)

    Brodeur, M.; Nicoloff, C.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Gupta, Y. K.; Hall, M. R.; Hall, O.; Hu, J.; Kelly, J. M.; Kolata, J. J.; Long, J.; O'Malley, P.; Schultz, B. E.

    2016-02-01

    Background: The precise determination of f t values for superallowed mixed transitions between mirror nuclide are gaining attention as they could provide an avenue to test the theoretical corrections used to extract the Vu d matrix element from superallowed pure Fermi transitions. The 17F decay is particularly interesting as it proceeds completely to the ground state of 17O, removing the need for branching ratio measurements. The dominant uncertainty on the f t value of the 17F mirror transition stems from a number of conflicting half-life measurements. Purpose: A precision half-life measurement of 17F was performed and compared to previous results. Methods: The life-time was determined from the β counting of implanted 17F on a Ta foil that was removed from the beam for counting. The 17F beam was produced by transfers reaction and separated by the TwinSol facility of the Nuclear Science Laboratory of the University of Notre Dame. Results: The measured value of t1/2 new=64.402 (42) s is in agreement with several past measurements and represents one of the most precise measurements to date. In anticipation of future measurements of the correlation parameters for the decay and using the new world average t1/2 world=64.398 (61) s, we present a new estimate of the mixing ratio ρ for the mixed transition as well as the correlation parameters based on assuming Standard Model validity. Conclusions: The relative uncertainty on the new world average for the half-life is dominated by the large χ2=31 of the existing measurements. More precision measurements with different systematics are needed to remedy to the situation.

  18. Thyroid fractional deposition and half life of radioiodine

    International Nuclear Information System (INIS)

    Fujita, Minoru

    1974-01-01

    In order to measure the absorbed dose of radioiodine in the thyroid gland, which was incorporated by halation or ingestion, iodine intake (fa), 131 I thyroid uptake rate(fw), 131 I thyroid uptake rate compared to the rate in the whole body (f 2 ) and the half life of iodine in the thyroid gland(Teff) were examined. Thyroid fractional deposition of 131 I was compared between Japanese and European. The rate of 131 I which moved from the blood into the thyroid gland in children (f 2 ') and the effect of the iodine in meals on 131 I thyroid uptake (fw) were also studied. In Japanese, f 2 was 0.28 and the mean Teff was 6.9 +- 0.7 days in 11 Japanese adults. There was an individual difference in these biological parameter and the values in adults were different from those in children. A little difference in value between Japanese and European suggested to be caused by the greater amount of stable iodine in meals in Japanese. (Serizawa, K.)

  19. A formula for half-life of proton radioactivity

    Science.gov (United States)

    Zhang, Zhi-Xing; Dong, Jian-Min

    2018-01-01

    We present a formula for proton radioactivity half-lives of spherical proton emitters with the inclusion of the spectroscopic factor. The coefficients in the formula are calibrated with the available experimental data. As an input to calculate the half-life, the spectroscopic factor that characterizes the important information on nuclear structure should be obtained with a nuclear many-body approach. This formula is found to work quite well, and in better agreement with experimental measurements than other theoretical models. Therefore, it can be used as a powerful tool in the investigation of proton emission, in particular for experimentalists. Supported by National Natural Science Foundation of China (11435014, 11405223, 11675265, 11575112), the 973 Program of China (2013CB834401, 2013CB834405), National Key Program for S&T Research and Development (2016YFA0400501), the Knowledge Innovation Project (KJCX2-EW-N01) of Chinese Academy of Sciences, the Funds for Creative Research Groups of China (11321064) and the Youth Innovation Promotion Association of Chinese Academy of Sciences

  20. Ubiquitin-fusion as a strategy to modulate protein half-life: A3G antiviral activity revisited

    International Nuclear Information System (INIS)

    Cadima-Couto, Iris; Freitas-Vieira, Acilino; Nowarski, Roni; Britan-Rosich, Elena; Kotler, Moshe; Goncalves, Joao

    2009-01-01

    The human APOBEC3G (A3G) is a potent inhibitor of HIV-1 replication and its activity is suppressed by HIV-1 virion infectivity factor (Vif). Vif neutralizes A3G mainly by inducing its degradation in the proteasome and blocking its incorporation into HIV-1 virions. Assessing the time needed for A3G incorporation into virions is, therefore, important to determine how quickly Vif must act to induce its degradation. We show that modelling the intracellular half-life of A3G can induce its Vif-independent targeting to the ubiquitin-proteasome system. By using various amino acids (X) in a cleavable ubiquitin-X-A3G fusion, we demonstrate that the half-life (t1/2) of X-A3G can be manipulated. We show that A3G molecules with a half-life of 13 min are incorporated into virions, whereas those with a half-life shorter than 5 min were not. The amount of X-A3G incorporated into virions increases from 13 min (Phe-A3G) to 85 min (Asn-A3G) and remains constant after this time period. Interestingly, despite the presence of similar levels of Arg-A3G (t1/2 = 28 min) and Asp-A3G (t1/2 = 65 min) into HIV-1 Δvif virions, inhibition of viral infectivity was only evident in the presence of A3G proteins with a longer half-life (t1/2 ≥ 65 min).

  1. Precise half-life measurement of the superallowed emitter 30S

    Science.gov (United States)

    Iacob, V. E.; Hardy, J. C.; Chen, L.; Horvat, V.; Bencomo, M.; Nica, N.; Park, H. I.; Roeder, B. T.; Saastamoinen, A.

    2018-03-01

    We have measured the half-life of 30S, the parent of a superallowed 0+→0+β transition, to a high precision using very pure sources and a 4 π proportional gas counter to detect the decay positrons. Our result for the half-life is 1.179 92(34) s. As a by-product of this measurement, we determine the half-life of its daughter, 30P, to be 2.501(2) min.

  2. On the 209Po half-life error and its confirmation. A critique

    International Nuclear Information System (INIS)

    Colle, R.; Colle, A.M.

    2016-01-01

    A recent report on 209 Po claimed to have made a determination of the 125-a half-life from measurements made over 0.8 % of one half-life. A careful reanalysis of the original data with a more complete and rigorous consideration of the underlying uncertainties demonstrates that this claim cannot withstand critical scrutiny. More importantly, this critique examines the larger issue as to what constitutes a valid half-life determination, and highlights that a careful and realistic analysis beyond the mere fitting of decay data to an exponential function is required for the measurement and reporting of half-life values. (author)

  3. The ecological half-life of 137Cs in undisturbed silt soil

    International Nuclear Information System (INIS)

    Drosg, M.

    2012-01-01

    The time necessary to safely cultivate agricultural areas after they have been contaminated by radioactivity (e.g. after the Chernobyl accident) is not determined by the physical half-life of the radioactive isotopes in question but by their (usually much shorter) ecological half-life (). This half-life not only depends on the type of soil but also on whether the soil was fertilized or not. Therefore it is not possible to determine an ecological half-life that is universally valid. However, the value for undisturbed, unfertilized soil should provide a general indication for the duration of ecological half-life. In a silt soil in Vienna, Austria, the ecological half-life of 137 Cs was determined to be 0.8 years, which is much shorter than the physical half-life of 30 years. - Highlights: ► Absolute measurements of 137 Cs radioactivity in leaves of perennial plants. ► The natural 40 K radioactivity served as reference. ► The ecological half-life of 137 Cs in loamy soil was determined.

  4. The half-life of 227Th by direct and indirect measurements

    International Nuclear Information System (INIS)

    Collins, S.M.; Pommé, S.; Jerome, S.M.; Ferreira, K.M.; Regan, P.H.; Pearce, A.K.

    2015-01-01

    Utilising a chemically purified solution the radioactive half-life of 227 Th has been determined indirectly by observation of the ingrowth of 223 Ra using an ionisation chamber (IC) and for the first time by direct observation of the change in activity with time using a high-purity germanium (HPGe) γ-ray spectrometer. The radioactive decay was observed for ~104 days (~5.6 half-lives) by γ-ray spectrometry and approximately 63 days and 72 days (~3.4 and ~3.9 half-lives) using an ionisation chamber (IC). The resulting half-life values – 18.695 (4) days (IC) and 18.683 (20) days (HPGe) – are consistent and detailed uncertainty budgets are presented for the two measurement techniques. A weighted mean of our results of 18.695 (4) days is inconsistent with the most precise published half-life value of 18.7176 (52) days (Jordan and Blanke, 1967). A critical evaluation of literature data has been performed, indicating a paucity of reliable and independent measurements. Selected independent published values have been used to determine a recommended half-life of 18.697 (7) days. A method has been introduced in the course of this work so that the recommended half-life of 227 Th as determined by ingrowth can be modified if a different 223 Ra half-life has been determined, evaluated and adopted. - Highlights: • First direct measurement of 227 Th half-life by HPGe γ-ray spectrometry. • Precision half-life measurement by ionisation chamber. • New half-life of 18.695 (4) days determined. • Critical evaluation of published half-lives and recommended value determined

  5. Half-life evaluations for 3H, 90Sr, and 90Y

    International Nuclear Information System (INIS)

    MacMahon, Desmond

    2006-01-01

    A recent paper has reviewed methods for the evaluation of discrepant sets of data and demonstrated the results of applying these methods to the published half-life data of 90 Sr and 137 Cs [MacMahon, T.D., Pearce, A., Harris, P., 2004. Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281]. The half-life data for 3 H has been subject to a comprehensive review and critical evaluation by Lucas and Unterweger [2000. Comprehensive review and critical evaluation of the half-life of tritium. J. Res. Natl. Inst. Stand. Technol. 105, 541-549]. The current paper reports the results of applying the various evaluation procedures of MacMahon et al. Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281] to the data of Lucas and Unterweger [Comprehensive review and critical evaluation of the half-life of tritium. J. Res. Natl. Inst. Stand. Technol. 105, 541-549], resulting in a recommended half-life of 4497(4) days. MacMahon et al. [Convergence of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281] highlighted problems in the evaluation of the discrepant half-life data of 90 Sr, in particular the worrying upward trend in the data, where the weighted mean of all the measurements increases, on average, by 35 days each time a new measurement result is added. The current paper reports on further analyses of these data. New measurements of the half-life of 90 Y have been reported by Kossert and Schrader [2004. Standardization by liquid scintillation counting and half-life measurements of 90 Y. Appl. Radiat. Isot. 60, 741]. This has prompted a new evaluation of all available published 90 Y half-life data. The data are fairly consistent, and a value of 64.063(16) h is recommended

  6. Update of NIST half-life results corrected for ionization chamber source-holder instability.

    Science.gov (United States)

    Unterweger, M P; Fitzgerald, R

    2014-05-01

    As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties. © 2013 Published by Elsevier Ltd.

  7. Infections and endothelial cells

    NARCIS (Netherlands)

    Keller, Tymen T.; Mairuhu, Albert T. A.; de Kruif, Martijn D.; Klein, Saskia K.; Gerdes, Victor E. A.; ten Cate, Hugo; Brandjes, Dees P. M.; Levi, Marcel; van Gorp, Eric C. M.

    2003-01-01

    Systemic infection by various pathogens interacts with the endothelium and may result in altered coagulation, vasculitis and atherosclerosis. Endothelium plays a role in the initiation and regulation of both coagulation and fibrinolysis. Exposure of endothelial cells may lead to rapid activation of

  8. Update of NIST half-life results corrected for ionization chamber source-holder instability

    International Nuclear Information System (INIS)

    Unterweger, M.P.; Fitzgerald, R.

    2014-01-01

    As reported at the ICRM 2011, it was discovered that the source holder used for calibrations in the NIST 4πγ ionization chamber (IC) was not stable. This has affected a large number of half-life measurement results previously reported and used in compilations of nuclear data. Corrections have been made on all of the half-life data based on the assumption that the changes to the ionization chamber response were gradual. The corrections are energy dependent and therefore radionuclide specific. This presentation will review our results and present the recommended changes in half-life values and/or uncertainties. - Highlights: • The NIST half-life data is corrected for sample positioning variations and refitted. • These results are reported and increased errors in the reported values are given. • Longer lived radionuclides are discussed

  9. Influence of sex and age on the biological half-life of cadmium in mice

    International Nuclear Information System (INIS)

    Taguchi, T.; Suzuki, S.

    1981-01-01

    The influence of age on the whole-body biological half-life of 109 Cd was studied in male mice following ip injection. The influence of sex on whole-body and organ retention was ascertained after sc injection. The whole-body biological half-life of 109 Cd of the older mice was more than twice that of the younger mice, and that of the female mice was longer than that of the males. These differences demonstrate a biological difference between males and females with respect to whole-body half-life of 109 Cd. The effects of age and sex on the biological half-life of Cd in mice are assessed quantitatively

  10. The HP 9825 A program for the determination of an isotope half-life

    International Nuclear Information System (INIS)

    Jujuratisbela, Uju.

    1980-01-01

    Determination of half life of gold 198, indium 116, manganese 56, copper 64 are presented, using least squares method in HP 9825 A. This method is more accurate and needs less time than graphic method. (author tr.)

  11. Designing of peptides with desired half-life in intestine-like environment

    KAUST Repository

    Sharma, Arun; Singla, Deepak; Rashid, Mamoon; Raghava, Gajendra Pal Singh

    2014-01-01

    hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical

  12. Standardization of 40 K by liquid scintillation counting. Determination of the half-life

    International Nuclear Information System (INIS)

    Grau Carles, A.; Grau Malonda, A.

    1997-01-01

    The relative abundance of the natural radioisotope ''40 K in environmental samples frequently generates interferences in low activity measurements. In the present study we propose the determination of ''40 K by the CIEMAT/NIST method. On this context, the verification of ''40 K half-life is required. We present a half-life value obtained by liquid scintillation counting in excellent agreement with those reported in the literature. (Author)

  13. ESOL facility for the generation and radiochemical separation of short half-life fission products

    International Nuclear Information System (INIS)

    Gehrke, R.J.; Meikrantz, D.H.; Baker, J.D.; Anderl, R.A.; Novick, V.J.; Greenwood, R.C.

    1988-01-01

    A facility has been developed at the Idaho National Engineering Laboratory (INEL) for the generation and rapid radiochemical separation of short half-life mixed fission products. This facility, referred to as the Idaho Elemental Separation On Line (ESOL), consists of electro-plated sources of spontaneously fissioning 252 Cf with a helium jet transport arrangement to continuously deliver short half-life, mixed fission products to the radiochemistry laboratory for rapid, computer controlled, radiochemical separations. 18 refs., 13 figs

  14. Using gamma distribution to determine half-life of rotenone, applied in freshwater

    Energy Technology Data Exchange (ETDEWEB)

    Rohan, Maheswaran, E-mail: mrohan@aut.ac.nz [Department of Biostatistics and Epidemiology, Auckland University of Technology, Auckland (New Zealand); Fairweather, Alastair; Grainger, Natasha [Science and Capability, Department of Conservation, Hamilton (New Zealand)

    2015-09-15

    Following the use of rotenone to eradicate invasive pest fish, a dynamic first-order kinetic model is usually used to determine the half-life and rate at which rotenone dissipated from the treated waterbody. In this study, we investigate the use of a stochastic gamma model for determining the half-life and rate at which rotenone dissipates from waterbodies. The first-order kinetic and gamma models produced similar values for the half-life (4.45 days and 5.33 days respectively) and days to complete dissipation (51.2 days and 52.48 days respectively). However, the gamma model fitted the data better and was more flexible than the first-order kinetic model, allowing us to use covariates and to predict a possible range for the half-life of rotenone. These benefits are particularly important when examining the influence that different environmental factors have on rotenone dissipation and when trying to predict the rate at which rotenone will dissipate during future operations. We therefore recommend that in future the gamma distribution model is used when calculating the half-life of rotenone in preference to the dynamic first-order kinetics model. - Highlights: • We investigated the use of the gamma model to calculate the half-life of rotenone. • Physical and environmental variables can be incorporated into the model. • A method for calculating the range around a mean half-life is presented. • The model is more flexible than the traditionally used first-order kinetic model.

  15. Variation in absorption and half-life of hydrocortisone influence plasma cortisol concentrations.

    Science.gov (United States)

    Hindmarsh, Peter C; Charmandari, Evangelia

    2015-04-01

    Hydrocortisone therapy should be individualized in congenital adrenal hyperplasia (CAH) patients to avoid over and under replacement. We have assessed how differences in absorption and half-life of cortisol influence glucocorticoid exposure. Forty-eight patients (21 M) aged between 6·1 and 20·3 years with CAH due to CYP21A2 deficiency were studied. Each patient underwent a 24-h plasma cortisol profile with the morning dose used to calculate absorption parameters along with an intravenous (IV) hydrocortisone (15 mg/m(2) body surface area) bolus assessment of half-life. Parameters derived were maximum plasma concentration (Cmax ), time of maximum plasma concentration (tmax ), time to attaining plasma cortisol concentration cortisol. Mean half-life was 76·5 ± 5·2 (range 40-225·3) min, Cmax 780·7 ± 61·6 nmol/l and tmax 66·7 (range 20-118) min. Time taken to a plasma cortisol concentration less than 100 nmol/l was 289 (range 140-540) min. Those with a fast half-life and slow tmax took longest to reach a plasma cortisol concentration less than 100 nmol/l (380 ± 34·6 min), compared to those with a slow half-life and fast tmax (298 ± 34·8 min) and those with a fast half-life and fast tmax (249·5 ± 14·4 min) (One-way anovaF = 4·52; P = 0·009). Both rate of absorption and half-life of cortisol in the circulation play important roles in determining overall exposure to oral glucocorticoid. Dose regimens need to incorporate estimates of these parameters into determining the optimum dosing schedule for individuals. © 2014 John Wiley & Sons Ltd.

  16. 18F half-life measurement using a high-purity germanium detector

    International Nuclear Information System (INIS)

    Han, Jubong; Lee, K.B.; Park, T.S.; Lee, J.M.; Oh, P.J.; Lee, S.H.; Kang, Y.S.; Ahn, J.K.

    2012-01-01

    The half-life of 18 F has been measured using HPGe detectors with a 137 Cs reference source. The counting ratio of 511 keV γ-rays from 18 F to 622 keV γ-rays from 137 Cs was fitted for the half-life with a weighted least-square method. Uncertainties due to the systematic effects arising from the measurement of a high activity 18 F source were studied in detail. The half-life of 18 F was found to be (109.72±0.19) min. The result is in a good agreement with the recommended value of (109.728±0.019) min evaluated at the Laborotaire National Henri Becquerel (LNHB). - Highlights: ► The 18 F half-life was measured with a reference source and without it using HPGe detectors. ► We found the systematic effect ‘activity dynamic range effect’ by monitoring the counts of the reference source. ► This activity dynamic range effect was corrected by using the reference source method. ► The 18 F half-life using the reference source method was in a good agreement with the recommended value of LNHB.

  17. The half-life of 207Bi and decays of 211At and 211Po

    International Nuclear Information System (INIS)

    Yanokura, M.; Kudo, H.; Nakahara, H.; Miyano, K.; Ohya, S.; Nitoh, O.

    1978-01-01

    The half-life of 207 Bi was obtained from the genetic relation between 207 Po and 207 Bi, and between 211 At and 207 Bi. The half-life was found to be 33.4 +- 0.8 y. The half-life of 207 Po was determined to be 5.81 +- 0.04 h by following the decay of the characteristic γ-rays from 207 Po. The half-life of 211 At was determined to be 7.23 +- 0.02 h by following the decay of γ-rays and α-particles from 211 At and 211 Po. The half-lives determined in the present work for 207 Po and 211 At agree with the literature although the half-life of 207 Bi differs considerably from the currently accepted value of 38 y. The branching ratio of 211 At decaying through EC and α-decay modes was determined together with the branching ratios of the three α-particles emitted from 211 Po. (Auth.)

  18. Re-measurement of the half-life of sup 7 sup 9 Se

    CERN Document Server

    Jiang Song Sheng; Diao Li Jun; Li Chun Shen; GouJingRu; Wu Shao Yon

    2002-01-01

    A new attempt has been made for the re-measurement of the half-life of sup 7 sup 9 Se. We made two major improvements over our earlier sup 7 sup 9 Se half-life determination (Nucl. Instr. and Meth. B 123 (1997) 403). Firstly, the half-life of sup 7 sup 9 Se was measured relative to the precisely known half-life of sup 7 sup 5 Se, rather than an absolute measurement of sup 7 sup 9 Se/Se. Secondly, the Projectile X-ray Detection technique was used for the separation of sup 7 sup 9 Se from its isobar, sup 7 sup 9 Br, rather than measuring sup 8 sup 1 Br for the deduction of sup 7 sup 9 Br interference, and this technique was also used for separation of sup 7 sup 5 Se and its isobar, sup 7 sup 5 As. A detailed description of the sample preparations, experimental setup and measurements are given. The re-measured half-life of sup 7 sup 9 Se was (2.95+-0.38)x10 sup 5 a, about a factor of 3 lower than the previous value, 1.1x10 sup 6 a. The problems in the previous measurement are discussed.

  19. High-precision half-life determination for the superallowed β+ emitter Ga62

    Science.gov (United States)

    Grinyer, G. F.; Finlay, P.; Svensson, C. E.; Ball, G. C.; Leslie, J. R.; Austin, R. A. E.; Bandyopadhyay, D.; Chaffey, A.; Chakrawarthy, R. S.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kanungo, R.; Leach, K. G.; Mattoon, C. M.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Sarazin, F.; Savajols, H.; Schumaker, M. A.; Wong, J.

    2008-01-01

    The half-life of the superallowed β+ emitter Ga62 has been measured at TRIUMF's Isotope Separator and Accelerator facility using a fast-tape-transport system and 4π continuous-flow gas proportional counter to detect the positrons from the decay of Ga62 to the daughter Zn62. The result, T1/2=116.100±0.025 ms, represents the most precise measurement to date (0.022%) for any superallowed β-decay half-life. When combined with six previous measurements of the Ga62 half-life, a new world average of T1/2=116.121±0.021 ms is obtained. This new half-life measurement results in a 20% improvement in the precision of the Ga62 superallowed ft value while reducing its mean by 0.9σ to ft=3074.3(12) s. The impact of this half-life measurement on precision tests of the CVC hypothesis and isospin symmetry breaking corrections for A⩾62 superallowed decays is discussed.

  20. Determination of plutonium-241 half-life by mass spectrometric measurement

    International Nuclear Information System (INIS)

    Hiyama, Takashi; Wada, Yukio; Onishi, Koichi

    1982-01-01

    Much data for Pu-241 half-life have been reported, but these values range from 13.8 years to 15.1 years depending on investigators. In order to define the half-life of Pu-241, the half-life was calculated by analyzing the mass spectrometry data obtained in the author's laboratory over the past six years on Plutonium Isotopic Standard Reference Materials prepared at the National Bureau of Standards (NBS). The sample used for this work consisted of SRM-947 and SRM-948 prepared at NBS. Before mass spectrometric analysis, the plutonium aliquot was separated from its Am-241 daughter by anion exchange chromatography, since Am-241 is not distinguished from Pu-241 in the mass spectrometer. 241 Pu/ 239 Pu and 241 Pu/ 240 Pu ratios were calculated from the values of mass spectrometric measurement. From the relation of log N to time, the half-life of Pu-241 was determined, based on the slope using a least squares fit. The half-life of Pu-241 was estimated to be 14.29+-0.15 years. (Yoshitake, I.)

  1. An albumin-oligonucleotide assembly for potential combinatorial drug delivery and half-life extension applications

    DEFF Research Database (Denmark)

    Kuhlmann, Matthias; Hamming, Jonas Bohn Refslund; Voldum, Anders

    2017-01-01

    The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in wh...... technology platform that offers potential combinatorial drug delivery and half-life extension applications.......The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach......, in which the 3' or 5' end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays...

  2. Improving the control of systematic uncertainties in precision measurements of radionuclide half-life

    International Nuclear Information System (INIS)

    Towers, S.

    2013-01-01

    Many experiments designed to precisely determine the half-life of a radionuclide employ a long lived reference source to help determine the impact on the data of any systematic variation in the detector and associated electronics. The half-life of the radionuclide of interest is determined from the ratio of its decay rate data to the decay rate data from the reference source. This correction procedure assumes that any underlying systematic affects the data and reference measurements in exactly the same way. In this paper we show that when some systematic effects affect the two differently, the ratio procedure can leave artifacts in the corrected data that can compromise an unbiased and precise assessment of the radionuclide half-life. We describe two methods that can help overcome this problem. We also describe several statistical tests that help determine which effects may underlie systematic variations in the data. We discuss an illustrative example based on previously published 32 Si and 36 Cl data recorded by an experiment at Brookhaven National Laboratory. We correct the data for systematic variation related to climate variation and estimate the 32 Si half-life to be T 1/2 =171.8±1.8. The reduction in uncertainty in the 32 Si half-life, relative to the previous estimate based upon this data, is equivalent to that which would be achieved through increasing the size of the data set by almost 3.5 times. - Author-Highlights: • Isotope decay data and reference source data can have differing systematics. • Differing systematics can inflate uncertainty of isotope half-life estimate. • We describe two methods to overcome this problem. • We describe statistical tests to determine which variables cause systematics. • We analyze Brookhaven 32Si/36Cl decay data as an illustrative example

  3. Precision half-life measurement of 11C: The most precise mirror transition F t value

    Science.gov (United States)

    Valverde, A. A.; Brodeur, M.; Ahn, T.; Allen, J.; Bardayan, D. W.; Becchetti, F. D.; Blankstein, D.; Brown, G.; Burdette, D. P.; Frentz, B.; Gilardy, G.; Hall, M. R.; King, S.; Kolata, J. J.; Long, J.; Macon, K. T.; Nelson, A.; O'Malley, P. D.; Skulski, M.; Strauss, S. Y.; Vande Kolk, B.

    2018-03-01

    Background: The precise determination of the F t value in T =1 /2 mixed mirror decays is an important avenue for testing the standard model of the electroweak interaction through the determination of Vu d in nuclear β decays. 11C is an interesting case, as its low mass and small QE C value make it particularly sensitive to violations of the conserved vector current hypothesis. The present dominant source of uncertainty in the 11CF t value is the half-life. Purpose: A high-precision measurement of the 11C half-life was performed, and a new world average half-life was calculated. Method: 11C was created by transfer reactions and separated using the TwinSol facility at the Nuclear Science Laboratory at the University of Notre Dame. It was then implanted into a tantalum foil, and β counting was used to determine the half-life. Results: The new half-life, t1 /2=1220.27 (26 ) s, is consistent with the previous values but significantly more precise. A new world average was calculated, t1/2 world=1220.41 (32 ) s, and a new estimate for the Gamow-Teller to Fermi mixing ratio ρ is presented along with standard model correlation parameters. Conclusions: The new 11C world average half-life allows the calculation of a F tmirror value that is now the most precise value for all superallowed mixed mirror transitions. This gives a strong impetus for an experimental determination of ρ , to allow for the determination of Vu d from this decay.

  4. The impact of extended half-life versus conventional factor product on hemophilia caregiver burden.

    Science.gov (United States)

    Schwartz, Carolyn E; Powell, Victoria E; Su, Jun; Zhang, Jie; Eldar-Lissai, Adi

    2018-05-01

    Extended half-life factor products have reduced annualized bleeding rates in hemophilia patients. The impact of extended half-life versus conventional factor products on hemophilia caregiver burden has not been investigated. This study aimed to evaluate caregiver burden in extended half-life versus conventional factor products for hemophilia A and B. This cross-sectional web-based study of caregivers of people with hemophilia A or B was recruited from a panel research company and by word of mouth. Participants completed the Hemophilia Caregiver Impact measure, the PedsQL Family Impact Module (PedsQL), and the Work Productivity and Activity Impairment Questionnaire (WPAI). We also collected demographic, insurance coverage, and medical information related to the hemophilia patient(s). Burden differences were assessed using linear regression and matched cohort analyses. The sample (n = 448) included 49 people who were caring for people on extended half-life factor products. Worse caregiver burden was associated with more infusions per week and more bleeds in the past 6 months. Regression analyses suggested that caring for someone who is on a extended half-life factor product is associated with lower emotional impact (β = - 0.11, p factor product had lower Emotional Impact and Practical Impact scores (t = - 2.95 and - 2.94, respectively, p factor product infusions of extended half-life factor products appears to reduce the emotional distress and practical burden of caregiving. Future work should evaluate the longitudinal impact.

  5. Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

    Science.gov (United States)

    Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa

    2016-06-01

    The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  6. Tests of a Fast Plastic Scintillator for High-Precision Half-Life Measurements

    Science.gov (United States)

    Laffoley, A. T.; Dunlop, R.; Finlay, P.; Leach, K. G.; Michetti-Wilson, J.; Rand, E. T.; Svensson, C. E.; Grinyer, G. F.; Thomas, J. C.; Ball, G.; Garnsworthy, A. B.; Hackman, G.; Orce, J. N.; Triambak, S.; Williams, S. J.; Andreoiu, C.; Cross, D.

    2013-03-01

    A fast plastic scintillator detector is evaluated for possible use in an ongoing program of high-precision half-life measurements of short lived β emitters. Using data taken at TRI-UMF's Isotope Separator and Accelerator Facility with a radioactive 26Na beam, a detailed investigation of potential systematic effects with this new detector setup is being performed. The technique will then be applied to other β-decay half-life measurements including the superallowed Fermi β emitters 10C, 14O, and T = 1/2 decay of 15O.

  7. Determination of half life of tellurium isotopes: a proposal for the teaching of nuclear physics

    International Nuclear Information System (INIS)

    Ruivo, Julio C.; Zamboni, Cibele B.; Batista, Wagner F.

    2013-01-01

    This work aimed at the development of courseware for teaching nuclear physics, using experimental data of half-life measurement (T1/2) of Tellurium isotopes (A=127 and 131). The choice of Tellurium was established for providing nuclear data, which are fundamental in related investigations of nuclear structure and its use in various areas such as geochemistry, chemical and pharmaceutical industries, astrophysics etc. For evaluation of the proposal performance, the material was made available, bringing a lot of information about nuclear safety, production and storage of radioactive material and concepts of radioactive decay, subatomic particles, emission of gamma radiation, half-life, etc.

  8. Determination of half life of tellurium isotopes: a proposal for the teaching of nuclear physics

    Energy Technology Data Exchange (ETDEWEB)

    Ruivo, Julio C.; Zamboni, Cibele B.; Batista, Wagner F., E-mail: julio.ruivo.costa@usp.br, E-mail: czamboni@ipen.br, E-mail: fisicawagner@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    This work aimed at the development of courseware for teaching nuclear physics, using experimental data of half-life measurement (T1/2) of Tellurium isotopes (A=127 and 131). The choice of Tellurium was established for providing nuclear data, which are fundamental in related investigations of nuclear structure and its use in various areas such as geochemistry, chemical and pharmaceutical industries, astrophysics etc. For evaluation of the proposal performance, the material was made available, bringing a lot of information about nuclear safety, production and storage of radioactive material and concepts of radioactive decay, subatomic particles, emission of gamma radiation, half-life, etc.

  9. Application of genetic algorithms for determination biological half-life of 137 Cs in milk

    International Nuclear Information System (INIS)

    Pantelic, G.

    1998-01-01

    Genetic algorithm an optimization method involving natural selection mechanisms, was used to determine biological half-life of sup 1 sup 3 sup 7 Cs in the milk, after the Chernobyl accident, based on a two compartment linear system model. Genetic algorithms operate on populations of strings. Reproduction, crossover and mutation are applied to successive string population to create new string population. A model parameter estimation is performed by minimizing square differences between fitting function and experimental data. The calculated biological half-life of sup 1 sup 3 sup 7 Cs in milk is (32(+(-) days (author)

  10. Study of the half-life of 123I and the determination of possible radionuclidic impurities

    International Nuclear Information System (INIS)

    Delgado, Jose Ubiratan; Araujo, Miriam Taina Ferreira de; Silva, Carlos Jose da; Araujo, Camila Cristina Cunha; Candido, Marcos Antonio; Pereira, Wagner do Prado

    2013-01-01

    During the process of production of the radiopharmaceutical nuclear reactor or cyclotron, impurities can be generated from biological, chemical and radionuclidic. The development of the present work was to study the half-life of Na 123 I sample produced in IEN (Institute of Nuclear Engineering) using the technique of gamma-ray spectrometry with germanium detector in order to Identify such impurities. The results Indicate values of half-life consistent with recent publications with a deviation of 0,08% and 0:11% of uncertainty as well as the identification of impurities to radionuclides 95m Tc, 96 Tc and 121 Te. (author)

  11. Biological Half-Life Measurements of Radioactive Strontium in Hormonal-Resistant Prostate Cancer Patients

    International Nuclear Information System (INIS)

    Haquin, G.; Riemer, T.; Kaniun, N.; Datz, H.; Yungreiss, Z.; Vexler, A.; Ben-Yosef, R.; Pelled, O.; German, U.; Marko, R.; Teshuva, A.; Kol, R.

    2004-01-01

    Therapy for metastatic bone pain in Hormonal-Resistant Prostate Cancer (HRPC) patients is performed by administering systemic radioisotope therapy [1]. The beta radiation emitted by the radioactive strontium 89 Sr [T 1/2 =50.5 d, E β (max)=1.49 MeV], an adequate radionuclide for this therapy procedure, irradiates the metastatic cells in the bone, producing the desired palliative effect. The beta disintegration of 89 Sr is followed by a low abundance (0.00945%) gamma ray with energy of 909 keV. The commercially available 89 Sr is in the form of Sr Cl and contains an impurity of less than 0.5% of 85 Sr [T 1/2 =64.8 d] ,which decays by electron capture, emitting gamma rays at 511 keV (95.71%). The radiation dose to the metastatic cells due to the gamma rays is negligible compared to the dose given by the beta radiation, assuming that the 89 Sr is concentrated at the metastatic bony lesions. Accurate information about retention and excretion of Sr in the patient's body will contribute to better evaluate the effectiveness of the treatment. he effective half-life of 89 Sr can be calculated either from Whole Body Counting (WBC) measurements or by measuring 85 Sr and/or 89 Sr in urine/blood. WBC measurements, using collimated HPGe detectors, allow the follow-up of 89 Sr and 85 Sr at different sites in the skeletal bones of the patient. Biological half-lives of Sr in different body sections measured by WBC and the correlation with excretion-rate-based biological half-lives are presented

  12. Advances in therapeutic Fc engineering - modulation of IgG associated effector functions and serum half-life

    Directory of Open Access Journals (Sweden)

    Abhishek Saxena

    2016-12-01

    Full Text Available Today monoclonal immunoglobulin gamma (IgG antibodies have become a major option in cancer therapy especially for the patients with advanced or metastatic cancers. Efficacy of monoclonal antibodies (mAbs are achieved through both its antigen binding fragment (Fab and crystallizable fragment (Fc. Fab can specifically recognize tumor associated antigen (TAA and thus modulate TAA-linked downstream signaling pathways that may lead to inhibition of tumor growth, induction of tumor apoptosis and differentiation. The Fc region can further improve mAbs’ efficacy by mediating effector functions such as antibody-dependent cellular cytotoxicity (ADCC, complement-dependent cytotoxicity (CDC and antibody dependent cell-mediated phagocytosis (ADCP. Moreover, Fc is the region interacting with the neonatal Fc receptor (FcRn in a pH-dependent manner that can slow down IgG’s degradation and extend its serum half-life. Loss of the antibody Fc region dramatically shortens its serum half-life and weakens its anti-cancer effects. Given the essential roles that the Fc region plays in the modulation of the efficacy of mAb in cancer treatment, Fc engineering has been extensively studied in the past years. This review focuses on the recent advances in therapeutic Fc engineering that modulates its related effector functions and serum half-life. We also discuss the progress made in aglycosylated mAb development that may substantially reduce cost of manufacture but maintain similar efficacies as conventional glycosylated mAb. Finally, we highlight several Fc engineering based mAbs under clinical trials.

  13. On the biological half-life of caesium in pregnant women and infants

    International Nuclear Information System (INIS)

    Rundo, J.; Turner, F.M.

    1992-01-01

    In the 1960s, changes were observed in the levels of 137 Cs in women who were pregnant or who had recently given birth. These were not associated with changes in the rate of fall-out, and were interpreted as the consequences of changes in the biological half-life. It was deduced that the biological half-life of caesium just before parturition averaged 59% of the value (87±33 days) after the birth of the baby; and that there was a step change at parturition. The behaviour of the levels during pregnancy suggested there was a gradual decrease in the biological half-life. Similar measurements were made in very young children. The concentration of the radionuclide in a breast-fed baby was usually a little less than that in the mother, indicating some discrimination in the transfer from plasma to milk; the concentration in a bottle-fed baby increased substantially and rapidly from the level at or shortly after birth. Data for three babies were sufficiently extensive to permit determination of the biological half-life in each. Values of 8.7±0.6 days, 15.4±1.1 days, and 14.9±3.6 days were derived. (author)

  14. Radionuclide biological half-life values for terrestrial and aquatic wildlife

    International Nuclear Information System (INIS)

    Beresford, N.A.; Beaugelin-Seiller, K.; Burgos, J.; Cujic, M.; Fesenko, S.; Kryshev, A.; Pachal, N.; Real, A.; Su, B.S.; Tagami, K.; Vives i Batlle, J.; Vives-Lynch, S.; Wells, C.; Wood, M.D.

    2015-01-01

    The equilibrium concentration ratio is typically the parameter used to estimate organism activity concentrations within wildlife dose assessment tools. Whilst this is assumed to be fit for purpose, there are scenarios such as accidental or irregular, fluctuating, releases from licensed facilities when this might not be the case. In such circumstances, the concentration ratio approach may under- or over-estimate radiation exposure depending upon the time since the release. To carrying out assessments for such releases, a dynamic approach is needed. The simplest and most practical option is representing the uptake and turnover processes by first-order kinetics, for which organism- and element-specific biological half-life data are required. In this paper we describe the development of a freely available international database of radionuclide biological half-life values. The database includes 1907 entries for terrestrial, freshwater, riparian and marine organisms. Biological half-life values are reported for 52 elements across a range of wildlife groups (marine = 9, freshwater = 10, terrestrial = 7 and riparian = 3 groups). Potential applications and limitations of the database are discussed. - Highlights: • 1907 biological half-life values have been collated for wildlife species. • Data cover 52 elements. • 27 marine, freshwater, riparian and terrestrial organisms are included.

  15. Intrinsically disordered segments and the evolution of protein half-life

    Science.gov (United States)

    Babu, M.

    2013-03-01

    Precise turnover of proteins is essential for cellular homeostasis and is primarily mediated by the proteasome. Thus, a fundamental question is: What features make a protein an efficient substrate for degradation? Here I will present results that proteins with a long terminal disordered segment or internal disordered segments have a significantly shorter half-life in yeast. This relationship appears to be evolutionarily conserved in mouse and human. Furthermore, upon gene duplication, divergence in the length of terminal disorder or variation in the number of internal disordered segments results in significant alteration of the half-life of yeast paralogs. Many proteins that exhibit such changes participate in signaling, where altered protein half-life will likely influence their activity. We suggest that variation in the length and number of disordered segments could serve as a remarkably simple means to evolve protein half-life and may serve as an underappreciated source of genetic variation with important phenotypic consequences. MMB acknowledges the Medical Research Council for funding his research program.

  16. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

    2017-01-01

    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  17. Effect of parent and daughter deformation on half-life time in exotic ...

    Indian Academy of Sciences (India)

    Shi and Swiatecki [6] put forward a model for exotic decay studies that uses Coulomb and proximity potential as interacting barrier for post-scission region and uses simple power law for overlap region. These authors [7] studied the effect of deformation of parent, daughter and shell attenuation on half-life time treating ...

  18. Dependence of the half-life of 221Fr on the implantation environment

    DEFF Research Database (Denmark)

    Olaizola, B.; Fraile, L.M.; Riisager, Karsten

    2010-01-01

    The possible dependence of the half-life of 221Fr on the solid-state environment has been investigated by the simultaneous measurement of implanted 221Fr ions in an insulator (Si) and a metallic substrate (Au) at the ISOLDE facility at CERN. Our results indicate that, if existing, the difference ...

  19. Precision half-life measurement of .sup.140 La with Ge-detector

    Czech Academy of Sciences Publication Activity Database

    Adam, Jindřich; Belov, A. G.; Brandt, R.; Chaloun, P.; Honusek, Milan; Kalinnikov, V. G.; Krivopustov, M. I.; Kulakov, B. A.; Langrock, E. J.; Pronskikh, V. S.; Sosnin, A. N.; Stegailov, V. I.; Tsoupko-Sitnikov, V. M.; Wan, J. S.; Westmeier, W.

    2002-01-01

    Roč. 187, - (2002), s. 419-426 ISSN 0168-583X R&D Projects: GA AV ČR KSK1048102 Keywords : radioastive nuclei * Ge-detectors * half-life measurements Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 1.158, year: 2002

  20. On the half-life of luminescence signals in dosimetric applications: A unified presentation

    Science.gov (United States)

    Pagonis, V.; Kitis, G.; Polymeris, G. S.

    2018-06-01

    Luminescence signals from natural and man-made materials are widely used in dosimetric and dating applications. In general, there are two types of half-lives of luminescence signals which are of importance to experimental and modeling work in this research area. The first type of half-life is the time required for the population of the trapped charge in a single trap to decay to half its initial value. The second type of half-life is the time required for the luminescence intensity to drop to half of its initial value. While there a handful of analytical expressions available in the literature for the first type of half-life, there are no corresponding analytical expressions for the second type. In this work new analytical expressions are derived for the half-life of luminescence signals during continuous wave optical stimulation luminescence (CW-OSL) or isothermal luminescence (ITL) experiments. The analytical expressions are derived for several commonly used luminescence models which are based on delocalized transitions involving the conduction band: first and second order kinetics, empirical general order kinetics (GOK), mixed order kinetics (MOK) and the one-trap one-recombination center (OTOR) model. In addition, half-life expressions are derived for a different type of luminescence model, which is based on localized transitions in a random distribution of charges. The new half-life expressions contain two parts. The first part is inversely proportional to the thermal or optical excitation rate, and depends on the experimental conditions and on the cross section of the relevant luminescence process. The second part is characteristic of the optical and/or thermal properties of the material, as expressed by the parameters in the model. A new simple and quick method for analyzing luminescence signals is developed, and examples are given of applying the new method to a variety of dosimetric materials. The new test allows quick determination of whether a set of

  1. Validation of effective half-life of tritium and computation of dose at Madras Atomic Power Station

    International Nuclear Information System (INIS)

    Moolya, L.L.; Kannan, R.K.; Sreekumaran Nair, B.; Mohandas, P.G.; Rajan, R.

    2001-01-01

    In Pressurised Heavy Water Reactors (PHWRs) tritium is produced by the activation of deuterium present in the moderator and coolant system. Hence, the inventory of tritium in PHWR is high and it contributes about 20 percent of the Station Dose. Tritium enters body by inhalation, ingestion and skin absorption. Dose received by an individual depends on its elimination rate from the body and hence the effective half-life. It is found that the effective half-life varies from person to person. The effective half-life also depends on the weather condition. The variation of effective half-life is taken care of in dose estimation by average method. However, in case of dose calculation for single uptake cases, there is a need to take fixed effective half-life. ICRP has taken the effective half-life as 10 days. The effective half-life is taken as 6 days in Indian conditions based on the studies conducted earlier in MAPS and elsewhere. Now with available data for about 16 years a fresh study was conducted to validate the effective half-life. This paper gives the study of effective half-life of tritium and its variation during different seasons of the year in MAPS. This paper also gives methods used for computing dose due to tritium. (author)

  2. A half-life the divided life of Bruno Pontecorvo, physicist or spy

    CERN Document Server

    Close, Frank

    2015-01-01

    Bruno Pontecorvo dedicated his career to hunting for the Higgs boson of his day: the neutrino, a nearly massless particle considered essential to the process of nuclear fission. His work on the Manhattan project under Enrico Fermi confirmed his reputation as a brilliant physicist and helped usher in the nuclear age. He should have won a Nobel Prize, but late in the summer of 1950 he vanished. At the height of the Cold War, Pontecorvo had disappeared behind the Iron Curtain. In Half-Life, physicist and historian Frank Close offers a heretofore untold history of Pontecorvo’s life, based on unprecedented access to his friends, family, and colleagues. With all the elements of a Cold War thriller—classified atomic research, an infamous double agent, a kidnapping by Soviet operatives—Half-Life is a history of particle physics at perhaps its most powerful: when it created the bomb.

  3. Determination of {sup 126}Sn half-life from ICP-MS and gamma spectrometry measurements

    Energy Technology Data Exchange (ETDEWEB)

    Bienvenu, P.; Arnal, N.; Comte, J. [CEA Cadarache DEN/DEC/SA3C/LARC, Paul Lez Durance (France); Ferreux, L.; Lepy, M.C.; Be, M.M. [CEA Saclay LIST LNE/LNHB, Gif sur Yvette (France); Andreoletti, G. [AREVA Cogema SL/UP2-800, Beaumont Hague (France)

    2009-07-01

    A new value of {sup 126}Sn half-life was determined by combination of inductively coupled plasma-mass spectrometry (ICP-MS) and gamma spectrometry measurements on purified sample solutions collected from nuclear fuel reprocessing. {sup 126}Sn was isolated through dissolution of fission product precipitates and liquid-liquid extraction with N-benzoyl-N-phenyl-hydroxylamine (BPHA). The abundance of {sup 126}Sn atoms together with the absence of interfering species in the analysed solutions made it possible to measure both mass concentration and nuclide activity with high precision and accuracy. This led to a {sup 126}Sn half-life value of 1.980 (57) x 10{sup 5} a. (orig.)

  4. High-Precision Half-Life Measurement for the Superallowed β+ Emitter Alm26

    Science.gov (United States)

    Finlay, P.; Ettenauer, S.; Ball, G. C.; Leslie, J. R.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Bandyopadhyay, D.; Cross, D. S.; Demand, G.; Djongolov, M.; Garrett, P. E.; Green, K. L.; Grinyer, G. F.; Hackman, G.; Leach, K. G.; Pearson, C. J.; Phillips, A. A.; Sumithrarachchi, C. S.; Triambak, S.; Williams, S. J.

    2011-01-01

    A high-precision half-life measurement for the superallowed β+ emitter Alm26 was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1/2=6346.54±0.46stat±0.60systms, consistent with, but 2.5 times more precise than, the previous world average. The Alm26 half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed β decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for Alm26, 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi β-decay studies used to test the conserved vector current hypothesis and determine the Vud element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

  5. High-Precision Half-life Measurements for the Superallowed β+ Emitter 14O

    Science.gov (United States)

    Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E. R.; Thomas, J. C.; Unsworth, C.

    2014-03-01

    The half-life of 14O, a superallowed Fermi β+ emitter, has been determined via simultaneous γ and β counting experiments at TRIUMF's Isotope Separator and Accelerator facility. Following the implantation of 14O samples at the center of the 8π spectrometer, a γ counting measurement was performed by detecting the 2313 keV γ-rays emitted from the first excited state of the daughter 14N using 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned directly behind the implantation site. The results, T½(γ) = 70:632 ± 0:094 s and T½(β) = 70:610 ± 0:030 s, are consistent with one another and, together with eight previous measurements, establish a new average for the 14O half-life of T½ = 70:619 ± 0:011 s with a reduced χ2 of 0.99.

  6. Half-life and intensities of photons of 103Pd isotope

    International Nuclear Information System (INIS)

    Popov, Yu.S.; Zakharova, L.V.; Kupriyanov, V.N.; Andreev, O.I.; Pakhomov, A.N.; Vakhetov, F.Z.

    2001-01-01

    Half-life and intensities of photons forming during 103 Pd isotope decay are determined by the methods of semiconductor x-ray and γ-spectrometry. 103 Pd is applied in nuclear medicine for preparation of 103m Rh isomer (T 1/2 =56 min) being used in irradiation of prostate neoplasms. Half-life of 103 Pd isotope is 16±0.6 days, relative intensities of x-ray and γ-photons are: K α /Kβ=5.1±0.4; 358 keV - 100 rel.units; 295 keV - 12.3±0.4 rel.units; 497 keV - 17.6±0.6 rel.units. Errors are represented for confidence probability 95 % [ru

  7. A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

    Science.gov (United States)

    Li, Z. X.; Zhao, W. W.

    2015-01-01

    The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

  8. Biological half-life of radiophosphorus in desert locust, Schistocerca gregaria Forskal (orthoptera:acrididae)

    International Nuclear Information System (INIS)

    Ulagaraj, S.M.; Singh, K.M.; Sethi, G.R.

    1975-01-01

    Adult desert locust, Schistocerca gregaria Forskal were fed with cabbage leaves, painted with carrier free 32 P 1mCi/ml. Radioactivity of five adults of both sexes and of feces was measured daily for 28 days. The amount of radioactivity appearing in the feces of males was consistently below that found in female locusts. The mean biological half-life of 32 P for males and females were 35.04 and 15.01 days, respectively. (author)

  9. Neutron activation analyses and half-life measurements at the usgs triga reactor

    Science.gov (United States)

    Larson, Robert E.

    Neutron activation of materials followed by gamma spectroscopy using high-purity germanium detectors is an effective method for making measurements of nuclear beta decay half-lives and for detecting trace amounts of elements present in materials. This research explores applications of neutron activation analysis (NAA) in two parts. Part 1. High Precision Methods for Measuring Decay Half-Lives, Chapters 1 through 8 Part one develops research methods and data analysis techniques for making high precision measurements of nuclear beta decay half-lives. The change in the electron capture half-life of 51Cr in pure chromium versus chromium mixed in a gold lattice structure is explored, and the 97Ru electron capture decay half-life are compared for ruthenium in a pure crystal versus ruthenium in a rutile oxide state, RuO2. In addition, the beta-minus decay half-life of 71mZn is measured and compared with new high precision findings. Density Functional Theory is used to explain the measured magnitude of changes in electron capture half-life from changes in the surrounding lattice electron configuration. Part 2. Debris Collection Nuclear Diagnostic at the National Ignition Facility, Chapters 9 through 11 Part two explores the design and development of a solid debris collector for use as a diagnostic tool at the National Ignition Facility (NIF). NAA measurements are performed on NIF post-shot debris collected on witness plates in the NIF chamber. In this application NAA is used to detect and quantify the amount of trace amounts of gold from the hohlraum and germanium from the pellet present in the debris collected after a NIF shot. The design of a solid debris collector based on material x-ray ablation properties is given, and calculations are done to predict performance and results for the collection and measurements of trace amounts of gold and germanium from dissociated hohlraum debris.

  10. Precise half-life measurement of the superallowed β+ emitter 38Km

    International Nuclear Information System (INIS)

    Ball, G. C.; Boisvert, G.; Bricault, P.; Churchman, R.; Dombsky, M.; Lindner, T.; Macdonald, J. A.; Vandervoort, E.; Bishop, S.; D'Auria, J. M.; Hardy, J. C.; Iacob, V. E.; Leslie, J. R.; Mak, H.-B.

    2010-01-01

    The half-life of 38 K m has been measured to be 924.46(14) ms, a result that is a factor of two more precise than any of the five previous measurements of this quantity. The previous results are not consistent with one another, but our result agrees well with the two most recent ones. The derived ft value for 38 K m is now one of the three most precisely known superallowed ft values.

  11. Increased Functional Half-life of Fibroblast Growth Factor-1 by Recovering a Vestigial Disulfide Bond

    Directory of Open Access Journals (Sweden)

    Jihun Lee

    2010-12-01

    Full Text Available The fibroblast growth factor (FGF family of proteins contains an absolutely conserved Cys residue at position 83 that is present as a buried free cysteine. We have previously shown that mutation of the structurally adjacent residue, Ala66, to cysteine results in the formation of a stabilizing disulfide bond in FGF-1. This result suggests that the conserved free cysteine residue at position 83 in the FGF family of proteins represents a vestigial half-cystine. Here, we characterize the functional half-life and mitogenic activity of the oxidized form of the Ala66Cys mutation to identify the effect of the recovered vestigial disulfide bond between Cys83 and Cys66 upon the cellular function of FGF-1. The results show that the mitogenic activity of this mutant is significantly increased and that its functional half-life is greatly extended. These favorable effects are conferred by the formation of a disulfide bond that simultaneously increases thermodynamic stability of the protein and removes a reactive buried thiol at position 83. Recovering this vestigial disulfide by introducing a cysteine at position 66 is a potentially useful protein engineering strategy to improve the functional half-life of other FGF family members.

  12. Measurements of Actual Effective Half - Life in 131I Therapy for Graves' Hyperthyroidism

    International Nuclear Information System (INIS)

    So, Yong Seon; Kim, Myung Seon; Kwon, Ki Hyun; Kim, Seok Whan; Kim, Tae Hyung; Han, Sang Woong; Kim, Eun Sil; Kim, Chong Soon

    1996-01-01

    Radioiodine[131I] has been used for the treatment of Graves' hyperthyroidism since the late 1940's and is now generally regarded as the treatment of choice for Graves' hyperthyroidism who does not remit following a course of antithyroid drugs. But for the dose given, several different protocols have been described by different centers, each attempting to reduce the incidence of long-term hypothyroidism while maintaining an acceptable rate control of Graves' hyperthyroidism. Our goals were to evaluate effective half-life and predict absorbed dose in Graves' hyperthyroidism patients, therefore, to calculate and read minister radioiodine activity needed to achieve aimed radiation dose. Our data showed that the mean effective 131I half-life for Graves' disease is 5.3 days(S.D=0.88) and mean biologic half-life is 21 days, range 9.5-67.2 days. The mean administered activity and the mean values of absorbed doses wet: 532 MBq(S.D.=254), 112 Gy (S.D.=50.9), respectively. The mean activity needed to achieve aimed radiation dose were 51 MBq and marked differences of 131I thyroidal uptake between tracer and therapy occurred in our study. We are sure that the dose calculation method that uses 5 days thyroidal 131I uptake measurements after tracer and therapy dose, provides sufficient data about the effective treatment in Graves' hyperthyroidism.

  13. Measurements of Actual Effective Half - Life in {sup 131}I Therapy for Graves' Hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    So, Yong Seon; Kim, Myung Seon; Kwon, Ki Hyun; Kim, Seok Whan; Kim, Tae Hyung; Han, Sang Woong; Kim, Eun Sil; Kim, Chong Soon [Hanil General Hospital, Seoul (Korea, Republic of)

    1996-03-15

    Radioiodine[131I] has been used for the treatment of Graves' hyperthyroidism since the late 1940's and is now generally regarded as the treatment of choice for Graves' hyperthyroidism who does not remit following a course of antithyroid drugs. But for the dose given, several different protocols have been described by different centers, each attempting to reduce the incidence of long-term hypothyroidism while maintaining an acceptable rate control of Graves' hyperthyroidism. Our goals were to evaluate effective half-life and predict absorbed dose in Graves' hyperthyroidism patients, therefore, to calculate and read minister radioiodine activity needed to achieve aimed radiation dose. Our data showed that the mean effective 131I half-life for Graves' disease is 5.3 days(S.D=0.88) and mean biologic half-life is 21 days, range 9.5-67.2 days. The mean administered activity and the mean values of absorbed doses wet: 532 MBq(S.D.=254), 112 Gy (S.D.=50.9), respectively. The mean activity needed to achieve aimed radiation dose were 51 MBq and marked differences of 131I thyroidal uptake between tracer and therapy occurred in our study. We are sure that the dose calculation method that uses 5 days thyroidal 131I uptake measurements after tracer and therapy dose, provides sufficient data about the effective treatment in Graves' hyperthyroidism.

  14. Fenobody: A Ferritin-Displayed Nanobody with High Apparent Affinity and Half-Life Extension.

    Science.gov (United States)

    Fan, Kelong; Jiang, Bing; Guan, Zhe; He, Jiuyang; Yang, Dongling; Xie, Ni; Nie, Guohui; Xie, Can; Yan, Xiyun

    2018-04-10

    Nanobodies consist of a single domain variable fragment of a camelid heavy-chain antibody. Nanobodies have potential applications in biomedical fields because of their simple production procedures and low cost. Occasionally, nanobody clones of interest exhibit low affinities for their target antigens, which, together with their short half-life limit bioanalytical or therapeutic applications. Here, we developed a novel platform we named fenobody, in which a nanobody developed against H5N1 virus is displayed on the surface of ferritin in the form of a 24mer. We constructed a fenobody by substituting the fifth helix of ferritin with the nanobody. TEM analysis showed that nanobodies were displayed on the surface of ferritin in the form of 6 × 4 bundles, and that these clustered nanobodies are flexible for antigen binding in spatial structure. Comparing fenobodies with conventional nanobodies currently used revealed that the antigen binding apparent affinity of anti-H5N1 fenobody was dramatically increased (∼360-fold). Crucially, their half-life extension in a murine model was 10-fold longer than anti-H5N1 nanobody. In addition, we found that our fenobodies are highly expressed in Escherichia coli, and are both soluble and thermo-stable nanocages that self-assemble as 24-polymers. In conclusion, our results demonstrate that fenobodies have unique advantages over currently available systems for apparent affinity enhancement and half-life extension of nanobodies. Our fenobody system presents a suitable platform for various large-scale biotechnological processes and should greatly facilitate the application of nanobody technology in these areas.

  15. Measurement of the half-life of sup 1 sup 7 sup 6 Lu

    CERN Document Server

    Nir-El, Y

    1998-01-01

    The half-life of sup 1 sup 7 sup 6 Lu was determined by measuring the disintegration rate of a solution of lutetium oxide, using a calibrated HPGe detector, and found to be (3.69+-0.02)x10 sup 1 sup 0 y. It is recommended that the current adopted value be calculated from the grouping of three published values since 1983, including our value, the weighted mean of which is (3.73+-0.01)x10 sup 1 sup 0 y.

  16. Half-life of the 3/2/sup +/ level of /sup 119/Sn

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, M C; Gil, F B [Faculdade de Ciencias da Universidade de Lisboa, Lisbon (Portugal). Grupo de Espectroscopia Nuclear, Laboratorio de Fisica

    1976-01-01

    The half-life of the 3/2/sup +/, 23.87 keV level of /sup 119/Sn is measured by the delayed coincidence technique. Magnetic spectrometry associated with scintillation techniques and scintillation spectrometry only have been used. The results obtained with these techniques were respectively Tsub(1/2) = 17.87 +- 0.11 ns and Tsub(1/2) = 18.48 +- 0.30 ns. The measured reduced M1 transition probability is compared with the single-particle and Kisslinger and Sorensen model predictions.

  17. The Half Life of the 53 keV Level in {sup 197}Pt

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S G

    1967-02-15

    The half life of the recently proposed 53 keV level in {sup 197}Pt has been measured to 18.5 {+-} 1.5 nsec using the delayed coincidence technique. This level, which is identified with the f{sub 5/2} single particle state, decays directly to the p{sub 1/2} ground state in {sup 197}Pt. The reduced E2 transition probability for this 53 keV transition has been deduced and compared with the results obtained for the corresponding transitions in other Pt, Hg, and Pb isotopes and with the theoretical predictions by Sorensen and by Wahlborn and Martinson.

  18. Dependence of radiocaesium biological half-life in freshwater fish on water potassium concentration and temperature

    International Nuclear Information System (INIS)

    Carreiro, M.C.V.; Corisco, J.A.G.

    1998-01-01

    Short-term experiments (35-49 days) showed that the rate of cesium elimination from fish increases with increasing potassium concentration in water (the biological half-life decreases); this, however, is only true of the potassium concentration range of 0.35 to 3.5 ppm, whereas higher potassium concentrations do not seem to affect the elimination rate. Decrease in water temperature within the 20 degC to 5 degC range slows down the cesium elimination process. (P.A.)

  19. First 0ν half-life limit from the Gotthard xenon time projection chamber

    International Nuclear Information System (INIS)

    Wong, H.T.; Boehm, F.; Fisher, P.

    1991-01-01

    A xenon Time Projection Chamber with an active volume of 207 liters has been built to study 0ν and 2ν double beta decay in 136 Xe. The TPC has been installed in the Gotthard Tunnel Underground Laboratory, and is currently taking data with 5 atm of xenon enriched in 62.5% 136 Xe. The first 166 hours of data are presented. Based on this data set, we deduce a half-life limit of T(0 + → 0 + ) > 6.2 x 10 21 years for the 0ν mode, at a 90% C.L. (author)

  20. Precision half-life determination of a mirror β transition: The decay of 31S

    International Nuclear Information System (INIS)

    Bacquias, A.; Kurtukian-Nieto, T.; Ascher, P.; Audirac, L.; Blank, B.; Giovinazzo, J.; Aeystoe, J.; Elomaa, V.V.; Eronen, T.; Hakala, J.; Jokinen, A.; Kankainen, A.; Karvonen, P.; Kolhinen, V.S.; Moore, I.D.; Rahaman, S.; Reponen, M.; Rissanen, J.; Saastamoinen, A.; Souin, J.

    2012-01-01

    The half-life of the mirror β decay of 31 S has been measured at the IGISOL facility at the University of Jyvaeskylae. The value obtained is T 1/2 ( 31 S)=(2553.4±1.8) ms, in agreement with previous measurements, but with a precision that is better by a factor of ten than the literature value previously adopted. When the new result is combined with the Q EC value measured recently at JYFLTRAP, a precision of better than 10 -3 is obtained for the ft value. (orig.)

  1. Determination of the half-life of sup 1 sup 0 sup 5 sup m Rh

    CERN Document Server

    Kronenberg, A K; Weber, R; Esterlund, R A; Patzelt, P

    1998-01-01

    Following a fast chemical separation of Ru isotopes from a fission-product mixture, sup 1 sup 0 sup 5 sup m Rh was periodically extracted from its precursor (4.44-h sup 1 sup 0 sup 5 Ru) for measurements of its half-life. The new value for the T sub 1 sub / sub 2 of sup 1 sup 0 sup 5 sup m Rh of (43.0+-0.3) s resolves the long-standing conflict in the literature between the two earlier measured values of 45 and 30 s.

  2. Effect of change in half-life of Se-79 on the safety of HLW geological disposal system

    International Nuclear Information System (INIS)

    Ishihara, Yoshinao; Ishiguro, Katsuhiko; Umeki, Hiroyuki

    1999-11-01

    Se-79 is one of key radionuclides in the performance assessment of the geological disposal system. Based on recent measurements, it is possible that the half-life of Se-79 will be changed longer than the present value in most handbooks and tables of isotopes. This study presents performance assessment calculations to investigate the overall effect of change in half-life of Se-79 on the repository system safety. The total system performance analyses for Se-79 were carried out, which focussed on the Reference-Case of the safety assessment in the H12 Project. As results, the maximum release rate in Becquerel unit of Se-79 from the engineered barrier system with new half-life decreases about one order of magnitude than that with half-life used so far. It is, however, that the maximum release rate in Becquerel unit of Se-79 from the natural barrier system is almost same for both half-life because of the channelling effects of groundwater flow. Consequently, the calculated maximum dose rate of Se-79 with new half-life does not change. It can be concluded that the change in half-life of Se-79 does not affect overall safety of the H12 disposal concept. (author)

  3. Isolation of human anti-serum albumin Fab antibodies with an extended serum-half life.

    Science.gov (United States)

    Kang, Hyeon-Ju; Kim, Hye-Jin; Cha, Sang-Hoon

    2016-01-01

    The serum albumin (SA) has been exploited to generate long-acting biotherapeutics by taking advantage of the FcRn-mediated recycling mechanism in a direct or an indirect way. Since Fab fragments have been proven to be clinically safe for human usage, we assumed that human anti-SA Fab antibodies could have a great potential as a carrier molecule to extend the serum half-life of therapeutic proteins. We, herein, had attempted to isolate anti-SA Fab antibodies from HuDVFab-8L antibody library via a phage display technology, and identified eight discrete human Fab antibodies. One of the Fab antibodies, SL335, showed the strongest binding reactivity to human SA with nM range of affinity at both pH 6 and pH 7.4, and cross-reacted to SAs from various species including rat, mouse, canine and monkey. The in vivo pharmacokinetic assay using a rat model indicated that SL335 has approximately 10 fold longer serum half-life and 26 to 44-fold increase in AUC0 → ∞ compared to the negative control Fab molecule in both intravenous and subcutaneous administrations. Knowing that Fabs have proven to be safe in clinics for a long time, SL335 seems to have a great potential in generating long-acting protein drugs by tagging effector molecules with either chemical conjugation or genetic fusion. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Preliminary measurements of the 87Rb half-life by means of the needle counter

    International Nuclear Information System (INIS)

    Zastawny, A.; Rabsztyn, B.

    1989-01-01

    In order to test the detector and to obtain the experience before starting the exact measurements, the measurements of 87 Rb half-life have been made. RbNO 3 produced by Merck was used to prepare the samples. The samples were prepared by evaporation of RbNO 3 water solution on an aluminium foil of 2,9 mg/cm 2 . The water solutions were changed in the range from (3286,4±1,8) x 10 -6 to (480,85±0,3) x 10 -6 . The background of the aluminium foil was equal to (0,117±0,007) cpm. In other measurements the back-scattering effect of 87 Rb beta rays on the aluminium foil amounted to 4%, as the measurements were performed in the 2π geometry. The diameters of samples were about 10 mm. The specific radioactivities of samples were measured versus the surface changed in the range (60-320) μg/cm 2 . The extrapolated value of the half-life, corrected for the chemical purity of the compound (as declared by the manufacterer) is equal to (4,86±0,1) x 10 10 years. This value is in good agreement with commonly accepted value of 4,88 x 10 10 years and with another last measurements. 10 refs., 1 fig., 2 tabs. (author)

  5. High-precision half-life measurements for the superallowed Fermi β+ emitter 14O

    Science.gov (United States)

    Laffoley, A. T.; Svensson, C. E.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Blank, B.; Bouzomita, H.; Cross, D. S.; Diaz Varela, A.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Grinyer, G. F.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Tardiff, E.; Thomas, J. C.; Unsworth, C.

    2013-07-01

    The half-life of the superallowed Fermi β+ emitter 14O has been determined via simultaneous direct β and γ counting experiments at TRIUMF's Isotope Separator and Accelerator (ISAC) facility. A γ-ray counting measurement was performed by detecting the 2312.6-keV γ rays emitted from an excited state of the daughter 14N following the implantation of samples at the center of the 8π γ-ray spectrometer, a spherical array of 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned behind the implantation site with a solid angle coverage of ˜20%. The results, T1/2(β)=70.610±0.030s and T1/2(γ)=70.632±0.094s, form a consistent set and, together with eight previous measurements, establish a new average for the 14O half-life of T1/2=70.619±0.011s with a reduced χ2 of 0.99.

  6. A new simplified allometric approach for predicting the biological half-life of radionuclides in reptiles

    International Nuclear Information System (INIS)

    Beresford, N.A.; Wood, M.D.

    2014-01-01

    A major source of uncertainty in the estimation of radiation dose to wildlife is the prediction of internal radionuclide activity concentrations. Allometric (mass-dependent) relationships describing biological half-life (T 1/2b ) of radionuclides in organisms can be used to predict organism activity concentrations. The establishment of allometric expressions requires experimental data which are often lacking. An approach to predict the T 1/2b in homeothermic vertebrates has recently been proposed. In this paper we have adapted this to be applicable to reptiles. For Cs, Ra and Sr, over a mass range of 0.02–1.5 kg, resultant predictions were generally within a factor of 6 of reported values demonstrating that the approach can be used when measured T 1/2b data are lacking. However, the effect of mass on reptilian radionuclide T 1/2b is minimal. If sufficient measured data are available for a given radionuclide then it is likely that these would give a reasonable estimate of T 1/2b in any reptile species. - Highlights: • An allometric approach to predict radionuclide T 1/2b values in reptiles is derived. • Predictions are generally within a factor of six of measured values. • Radionuclide biological half-life is in-effect mass independent

  7. Half-life data--a critical review of TECDOC-619 update

    International Nuclear Information System (INIS)

    Woods, M.J.; Collins, S.M.

    2004-01-01

    An accurate knowledge of selected nuclear decay data is critical to a wide range of processes involving radionuclides. An IAEA publication in 1991 was dedicated to the evaluation of half-lives and specific gamma-ray emission probabilities for 39 selected radionuclides considered to be important for detector efficiency calibrations. A new exercise was initiated in December 1998 to update this previous evaluation and to include a number of new radionuclides of interest; 62 radionuclides were considered along with specific parent-daughter combinations (to give a total of 64 radionuclides). That work is now being completed and a new set of recommended data is being prepared for publication. A critical comparison of the 1991 and 2003 half-life data suggests that there has not been any significant improvement in the accuracy of the recommended data. The possible reasons for this situation are discussed together with the evaluation procedure and the quality of the available data. Proposals are made for concerted actions that could lead to a significant improvement in these recommended half-life data

  8. Estimating the biological half-life for radionuclides in homoeothermic vertebrates: a simplified allometric approach

    Energy Technology Data Exchange (ETDEWEB)

    Beresford, N.A. [Lancaster Environment Centre, NERC Centre for Ecology and Hydrology, Lancaster (United Kingdom); Vives i Batlle, J. [Belgian Nuclear Research Centre, Mol (Belgium)

    2013-11-15

    The application of allometric, or mass-dependent, relationships within radioecology has increased with the evolution of models to predict the exposure of organisms other than man. Allometry presents a method of addressing the lack of empirical data on radionuclide transfer and metabolism for the many radionuclide-species combinations which may need to be considered. However, sufficient data across a range of species with different masses are required to establish allometric relationships and this is not always available. Here, an alternative allometric approach to predict the biological half-life of radionuclides in homoeothermic vertebrates which does not require such data is derived. Biological half-life values are predicted for four radionuclides and compared to available data for a range of species. All predictions were within a factor of five of the observed values when the model was parameterised appropriate to the feeding strategy of each species. This is an encouraging level of agreement given that the allometric models are intended to provide broad approximations rather than exact values. However, reasons why some radionuclides deviate from what would be anticipated from Kleiber's law need to be determined to allow a more complete exploitation of the potential of allometric extrapolation within radioecological models. (orig.)

  9. HALO--a Java framework for precise transcript half-life determination.

    Science.gov (United States)

    Friedel, Caroline C; Kaufmann, Stefanie; Dölken, Lars; Zimmer, Ralf

    2010-05-01

    Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo.

  10. A novel exendin-4 human serum albumin fusion protein, E2HSA, with an extended half-life and good glucoregulatory effect in healthy rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ling; Wang, Lin; Meng, Zhiyun; Gan, Hui; Gu, Ruolan; Wu, Zhuona; Gao, Lei; Zhu, Xiaoxia; Sun, Wenzhong; Li, Jian; Zheng, Ying; Dou, Guifang, E-mail: douguifang@vip.163.com

    2014-03-07

    Highlights: • E2HSA has an extended half-life and good plasma stability. • E2HSA could improve glucose-dependent insulin secretion. • E2HSA has excellent glucoregulatory effects in vivo. • E2HSA could potentially be used as a new long-acting GLP-1 receptor agonist for type 2 diabetes management. - Abstract: Glucagon-like peptide-1 (GLP-1) has attracted considerable research interest in terms of the treatment of type 2 diabetes due to their multiple glucoregulatory functions. However, the short half-life, rapid inactivation by dipeptidyl peptidase-IV (DPP-IV) and excretion, limits the therapeutic potential of the native incretin hormone. Therefore, efforts are being made to develop the long-acting incretin mimetics via modifying its structure. Here we report a novel recombinant exendin-4 human serum albumin fusion protein E2HSA with HSA molecule extends their circulatory half-life in vivo while still retaining exendin-4 biological activity and therapeutic properties. In vitro comparisons of E2HSA and exendin-4 showed similar insulinotropic activity on rat pancreatic islets and GLP-1R-dependent biological activity on RIN-m5F cells, although E2HSA was less potent than exendin-4. E2HSA had a terminal elimation half-life of approximate 54 h in healthy rhesus monkeys. Furthermore, E2HSA could reduce postprandial glucose excursion and control fasting glucose level, dose-dependent suppress food intake. Improvement in glucose-dependent insulin secretion and control serum glucose excursions were observed during hyperglycemic clamp test (18 h) and oral glucose tolerance test (42 h) respectively. Thus the improved physiological characterization of E2HSA make it a new potent anti-diabetic drug for type 2 diabetes therapy.

  11. High-precision half-life determination for 21Na using a 4 π gas-proportional counter

    Science.gov (United States)

    Finlay, P.; Laffoley, A. T.; Ball, G. C.; Bender, P. C.; Dunlop, M. R.; Dunlop, R.; Hackman, G.; Leslie, J. R.; MacLean, A. D.; Miller, D.; Moukaddam, M.; Olaizola, B.; Severijns, N.; Smith, J. K.; Southall, D.; Svensson, C. E.

    2017-08-01

    A high-precision half-life measurement for the superallowed β+ transition between the isospin T =1 /2 mirror nuclei 21Na and 21Ne has been performed at the TRIUMF-ISAC radioactive ion beam facility yielding T1 /2=22.4506 (33 ) s, a result that is a factor of 4 more precise than the previous world-average half-life for 21Na and represents the single most precisely determined half-life for a transition between mirror nuclei to date. The contribution to the uncertainty in the 21Na F tmirror value due to the half-life is now reduced to the level of the nuclear-structure-dependent theoretical corrections, leaving the branching ratio as the dominant experimental uncertainty.

  12. Study of the Bs meson and measurement of its half-life with the ALEPH detector

    International Nuclear Information System (INIS)

    Duarte, H.

    1994-01-01

    The B s 0 meson is the bound state of a quark anti-quark pair made up of a beauty particle and a strange particle. In the first chapter we review different experimental results leading to the existence of B S 0 meson and we draw the theoretical framework of the concept of beauty particles. The second chapter deals with the probability of the formation of a meson containing a strange quark during the fragmentation. This chapter also contains a re-analysis of the whole data constraining the mixing parameter B s 0 -B s 0 -bar. The relevancy of the analysis relies on the assumption that the B s 0 meson decays only into one D s , one lepton and one neutrino. The ALEPH detector is described in chapter 3, this four-pi, multi-particle detector is installed on the e + e - LEP (Large Electron Positron Collider). The signature selected for the measurement of the half-life is the combination of one D s in the decay modes: φπ, K *0 K with a lepton having opposite charge. This measurement implies the knowledge of the B s 0 momentum and of its flight length. In order to assess the momentum of the neutrino, a technique of measuring missing energy is presented in the chapter 4. The selection of B s 0 events is detailed in the chapter 5. A cutting limit on the energy of B s 0 based on the missing energy is used to deduce the production rate of B s 0 . In the chapter 6 we present the measurement of the half-life of B s 0 , the method used for the reconstruction of decay vertices and of the event main vertex is detailed. The validity of the method has been tested on Monte-Carlo simulations. The final result concerning the measurement of the half-life is: τ(B s )=[1.92(+0.45-0.35)±0.04] ps [fr

  13. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  14. Going Beyond the Binary : The body, Sexuality and Identity in Shelley Jackson’s Half Life: a novel

    OpenAIRE

    Liu, Linjing

    2012-01-01

    The thesis focuses on Shelley Jackson’s Half Life: a Novel with efforts directed towards a literary interpretation considering relevant issues within the context of gender and feminist theory. The argument rests upon four basic units: the theoretical framework at the outset, the question of the body next, thirdly an investigation of sexuality, and finally a consideration of identity. In Jackson’s Half Life: a Novel the non-dualist thinking underlies a deliberate play of dualism. To go beyond ...

  15. ORIGEN-S Decay Data Library and Half-Life Uncertainties

    International Nuclear Information System (INIS)

    Hermann, O.W.

    1998-01-01

    The results of an extensive update of the decay data of the ORIGEN-S library are presented in this report. The updated decay data were provided for both the ORIGEN-S and ORIGEN2 libraries in the same project. A complete edit of the decay data plus the available half-life uncertainties are included in Appendix A. A detailed description of the types of data contained in the library, the format of the library, and the data sources are also presented. Approximately 24% of the library nuclides are stable, 66% were updated from ENDF/B-VI, about 8% were updated from ENSDF, and the remaining 2% were not updated. Appendix B presents a listing of percentage changes in decay heat from the old to the updated library for all nuclides containing a difference exceeding 1% in any parameter

  16. The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions.

    Science.gov (United States)

    Glick, Matthew; Biddle, Perry; Jantzi, Josh; Weaver, Samantha; Schirch, Doug

    2014-09-12

    Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Half-life distribution table of radioactive nuclei; Table de distribution des periodes des noyaux radioactifs

    Energy Technology Data Exchange (ETDEWEB)

    Gugenberger, P [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1954-07-01

    This table allows to identify an element if its period is known. Data for this table were taken from the half-life values adopted by Hollander, PERLMAN and SEABORG (Rev. mod. Phys., 1953, 22 number 2). Moreover for each nucleus, the mass number, the charge number and the type of decay are given in the table. (author) [French] Cette table permet l'identification d'un element dont la periode est connue. Elle a ete etablie en utilisant les valeurs des periodes donnees par HOLLANDER, PERLMAN et SEABORG dans Rev. mod. Phys., 1953, 25 numero 2. On y trouve en outre, pour chaque nuclide, les caracteristiques suivantes: Z, A, modes de desintegration. (auteur)

  18. Development of CANDLES low background HPGe detector and half-life measurement of 180Tam

    Science.gov (United States)

    Chan, W. M.; Kishimoto, T.; Umehara, S.; Matsuoka, K.; Suzuki, K.; Yoshida, S.; Nakajima, K.; Iida, T.; Fushimi, K.; Nomachi, M.; Ogawa, I.; Tamagawa, Y.; Hazama, R.; Takemoto, Y.; Nakatani, N.; Takihira, Y.; Tozawa, M.; Kakubata, H.; Trang, V. T. T.; Ohata, T.; Tetsuno, K.; Maeda, T.; Khai, B. T.; Li, X. L.; Batpurev, T.

    2018-01-01

    A low background HPGe detector system was developed at CANDLES Experimental Hall for multipurpose use. Various low background techniques were employed, including hermatic shield design, radon gas suppression, and background reduction analysis. A new pulse shape discrimination (PSD) method was specially created for coaxial Ge detector. Using this PSD method, microphonics noise and background event at low energy region less than 200 keV can be rejected effectively. Monte Carlo simulation by GEANT4 was performed to acquire the detection efficiency and study the interaction of gamma-rays with detector system. For rare decay measurement, the detector was utilized to detect the nature's most stable isomer tantalum-180m (180Tam) decay. Two phases of tantalum physics run were completed with total livetime of 358.2 days, which Phase II has upgraded shield configuration. The world most stringent half-life limit of 180Tam has been successfully achieved.

  19. Half-life of each dioxin and PCB congener in the human body

    Energy Technology Data Exchange (ETDEWEB)

    Ogura, Isamura [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)

    2004-09-15

    It is well known that dioxin and PCB congeners accumulate in the human body. For assessing their toxicological risk, it is important to know the half-life of each congener in the human body. This study summarizes the overall half-lives of congeners in humans as reported in the literature, and compares them with the half-lives due to fecal and sebum excretions, as estimated by data on the concentrations of congeners in feces and sebum in the literature. In addition, the overall half-lives of congeners for the general Japanese population were estimated from the data on dietary intakes and concentrations in the human body reported by the municipalities.

  20. The beta(+) decay and cosmic-ray half-life of Mn-54

    Science.gov (United States)

    Dacruz, M. T. F.; Norman, E. B.; Chan, Y. D.; Garcia, A.; Larimer, R. M.; Lesko, K. T.; Stokstad, R. G.; Wietfeldt, F. E.

    1993-03-01

    We performed a search for the beta(+) branch of Mn-54 decay. As a cosmic ray, Mn-54, deprived of its atomic electrons, can decay only via beta(+) and beta(-) decay, with a half-life of the order of 106 yr. This turns Mn-54 into a suitable cosmic chronometer for the study of cosmic-ray confinement times. We searched for coincident back-to-back 511-keV gamma-rays using two germanium detectors inside a Nal(Tl) annulus. An upper limit of 2 x 10-8 was found for the beta(+) decay branch, corresponding to a lower limit of 13.7 for the log ft value.

  1. Precision measurement of the half-life of $^{109}$In in large and small lattice environments

    CERN Multimedia

    We propose to undertake high precision measurements of the half-life of $^{109}$In in large and small lattice environments to study the effect of compression on the electron capture nuclear decay rate. Such studies are of general interest having implications in many areas ranging from astrophysics to geophysics. At present, very little data is available on the change of electron capture decay rate under compression and the available data seems to indicate that the observed increase of the electron capture decay rate under compression is much greater than the predictions of the best available density functional calculations as obtained from TB-LMTO or WIEN2K codes. The proposed experiment should generate more data thus clarifying the experimental situation.

  2. Half-life distribution table of radioactive nuclei; Table de distribution des periodes des noyaux radioactifs

    Energy Technology Data Exchange (ETDEWEB)

    Gugenberger, P. [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1954-07-01

    This table allows to identify an element if its period is known. Data for this table were taken from the half-life values adopted by Hollander, PERLMAN and SEABORG (Rev. mod. Phys., 1953, 22 number 2). Moreover for each nucleus, the mass number, the charge number and the type of decay are given in the table. (author) [French] Cette table permet l'identification d'un element dont la periode est connue. Elle a ete etablie en utilisant les valeurs des periodes donnees par HOLLANDER, PERLMAN et SEABORG dans Rev. mod. Phys., 1953, 25 numero 2. On y trouve en outre, pour chaque nuclide, les caracteristiques suivantes: Z, A, modes de desintegration. (auteur)

  3. Development of a time-variable nuclear pulser for half life measurements

    International Nuclear Information System (INIS)

    Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.; Genezini, Frederico A.

    2013-01-01

    In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decay constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.

  4. Development of a time-variable nuclear pulser for half life measurements

    Energy Technology Data Exchange (ETDEWEB)

    Zahn, Guilherme S.; Domienikan, Claudio; Carvalhaes, Roberto P. M.; Genezini, Frederico A. [Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP. P.O. Box 11049, Sao Paulo, 05422-970 (Brazil)

    2013-05-06

    In this work a time-variable pulser system with an exponentially-decaying pulse frequency is presented, which was developed using the low-cost, open-source Arduino microcontroler plataform. In this system, the microcontroller produces a TTL signal in the selected rate and a pulse shaper board adjusts it to be entered in an amplifier as a conventional pulser signal; both the decay constant and the initial pulse rate can be adjusted using a user-friendly control software, and the pulse amplitude can be adjusted using a potentiometer in the pulse shaper board. The pulser was tested using several combinations of initial pulse rate and decay constant, and the results show that the system is stable and reliable, and is suitable to be used in half-life measurements.

  5. Accurate γ-ray spectrometry measurements of the half-life of 92Sr

    International Nuclear Information System (INIS)

    Leconte, P.; Hudelot, J.P.; Antony, M.

    2008-01-01

    Studies of the nuclear fuel cycle require an accurate knowledge of the energy release from the decay of radioactive nuclides produced in a reactor, including precise half-life data for the short-lived radionuclides. Moreover, short-lived fission products are crucial for fission rate distribution measurements performed in low-power facilities, such as EOLE and MINERVE of CEA Cadarache [Fougeras, P., 2005. EOLE, MINERVE and MASURCA facilities and their associated neutron experimental programs. In: 13th International Conference on Nuclear Engineering, Beijing, China, 16-20 May 2005], and their nuclear decay data need to be known to high precision. For these reasons, the half-life of 92 Sr has been measured to solve a recently observed inconsistency identified with the quoted value in the main nuclear applications libraries (including JEFF3.1): T 1/2 =2.71±0.01 h [Parsa, B., Ashari, A., Goolvard, L., Nobar, Y.M., 1971. Decay scheme of 2.71 h 92 Sr. Nucl. Phys. A 175, 629-640]. An overestimation of 4.5% has been identified in this work, based on two independent methods. Specific γ-ray spectrometry measurements on activated fissile foils have been carried out, using two HPGe detectors. Influencing factors such as net area measurements of photopeaks, pulse pile-up accuracy and dead time corrections in the presence of decaying activity are discussed. A new value has been obtained by combining eight series of measurements: T 1/2 =2.594±0.006 h. The uncertainty has been reduced by a factor of two with respect to previous evaluations. This measured value also shows good agreement with the most recent studies of T 1/2 =2.627±0.009 h [Nir-El, Y., 2003. Private Communications. Soreq Research Centre, Yavne, Israel

  6. Biological half-life of iodine in adults with intact thyroid function and in athyreotic persons

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, G.H.; Hauck, B.M.; Chamberlain, M.J

    2002-07-01

    A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of {sup 131}I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of {sup 131}I following its medical administration. The average biological half-life of {sup 131}I in 26 euthyroid subjects was found to be 66.1{+-}6.3 days which may be statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2{+-}8.6 days and in three hypothyroid patients the corresponding value was 29.3{+-}8.8 days. Thyroid {sup 131}I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck arteriorly. Measured values were 0.144{+-}0.009, 0.314{+-}0.035 and 0.045{+-}0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06-0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0{+-}0.2 days and 18.4{+-}1.1. days. (author)

  7. Calculation of chemical elimination half-life from blood with an ongoing exposure source: the example of perfluorooctanoic acid (PFOA).

    Science.gov (United States)

    Russell, Mark H; Waterland, Robert L; Wong, Fiona

    2015-06-01

    Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4-2.7) and 2.3years (95% CI, 2.1-2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20-30% over the period 1999-2008. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  9. Propose of a model for dose and hazard calculation due the Rn-222, Rn-220 and its short half-life daugthers inhalation

    International Nuclear Information System (INIS)

    Mauricio, C.L.P.

    1982-01-01

    The compartimental dosimetric model is used to simulate, by computer, the interactions of the inhalated radon atom radiations and its short half-life daugthers with cells. The metabolic trajectory of these radionuclides is described by differential equations of continuous medium dynamics, where the elements transform by radioactive decay. This work permits to determine the individual retenction function, beeing useful in radioprotection routines or emergence situations. The results of internal dosimetry are consistent with the new I.C.R.P. - 32 international recommendations. (L.C.) [pt

  10. Proposal of a new model for dose calculation due to the inhalation of Ru-222, Ru-220 and their sons with brief half-life

    International Nuclear Information System (INIS)

    Mauricio, C.L.P.

    1982-06-01

    The consequences of the radiation interactions upon the human body are studied. In order to simulate by computer the radiation interaction of the atoms of radon and thoron atoms and their Sons with a brief half life inhaled with the cells, the compartimental dosimetric model is used. The metabolic pathway of those radionuclides is described by continuous medium dynamic differential equation. The energy transfer processes are seen in details. The individual retention function is determined by bio-analysis. The results of internal dosimetry are consistents with the new international recommendations from ICRP-32. (L.F.S.) [pt

  11. Pre-Clinical Intravenous Serum Pharmacokinetics of Albumin Binding and Non-Half-Life Extended Nanobodies®

    Directory of Open Access Journals (Sweden)

    Sven Hoefman

    2015-07-01

    Full Text Available Nanobodies are antigen-binding, single variable domain proteins derived from naturally-occurring, heavy chain only antibodies. They are highly soluble, stable, and can be linked to build multi-specific formats. Several Nanobodies are currently in clinical development in different therapeutic areas, for both chronic and acute applications. For the former, prolonged exposure is achieved by half-life extending moieties that target endogenous albumin, while for the latter, non-half-life extended constructs are preferable. To demonstrate the general pharmacokinetic behavior of both formats, serum levels of seven intravenously administered Nanobodies were analyzed in cynomolgus monkeys, mice or rabbits. In monkeys, the total clearance of a monomeric irrelevant Nanobody was rapid (2.0 mL/(min*kg and approximated the species glomerular filtration rate, indirectly suggesting that the Nanobody was mainly eliminated via the kidneys. When linked to an anti-albumin Nanobody, a 376-fold decrease in clearance was observed, resulting in a terminal half-life of 4.9 days, corresponding to the expected species albumin half-life. Similar conclusions were drawn for (non- half-life extended mono-, bi- and trimeric Nanobodies in mice or rabbits, suggesting that these kinetic principles apply across species. Applying this knowledge to species translation and study design is crucial for successful pre-clinical development of novel therapeutic Nanobody candidates.

  12. Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life.

    Science.gov (United States)

    Adams, Ralph; Griffin, Laura; Compson, Joanne E; Jairaj, Mark; Baker, Terry; Ceska, Tom; West, Shauna; Zaccheo, Oliver; Davé, Emma; Lawson, Alastair Dg; Humphreys, David P; Heywood, Sam

    2016-10-01

    We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds HSA with similar affinity within the physiologically relevant range of pH 5.0 - pH 7.4, and does not have a deleterious effect on the binding of HSA to neonatal Fc receptor (FcRn). A crystal structure of humanized CA645 Fab in complex with HSA was solved and showed that CA645 Fab binds to domain II of HSA. Superimposition with the crystal structure of FcRn bound to HSA confirmed that CA645 does not block HSA binding to FcRn. In mice, the serum half-life of humanized CA645 Fab is 84.2 h. This is a significant extension in comparison with Fab variant. The Fab-HSA structure was used to design a series of mutants with reduced affinity to investigate the correlation between the affinity for albumin and serum half-life. Reduction in the affinity for MSA by 144-fold from 2.2 nM to 316 nM had no effect on serum half-life. Strikingly, despite a reduction in affinity to 62 µM, an extension in serum half-life of 26.4 h was still obtained. CA645 Fab and the CA645 Fab-HSA complex have been deposited in the Protein Data Bank (PDB) with accession codes, 5FUZ and 5FUO, respectively.

  13. Intrinsically Disordered Segments Affect Protein Half-Life in the Cell and during Evolution

    NARCIS (Netherlands)

    Lee, R.T.J.G. van der; Lang, B.; Kruse, K.; Gsponer, J.; Groot, N.; Huynen, M.A.; Matouschek, A.; Fuxreiter, M.; Babu, M.M.

    2014-01-01

    Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast,

  14. Ecological half-life of 137Cs in plants associated with a contaminated stream

    International Nuclear Information System (INIS)

    Peles, John D.; Smith, Michael H.; Lehr Brisbin, I.

    2002-01-01

    Ecological half-life (T e ) is a useful measure for studying the long-term decline of contaminants, such as radionuclides, in natural systems. The current investigation determined levels of radiocesium ( 137 Cs) in two aquatic (Polygonum punctatum, Sagittaria latifolia) and three terrestrial (Alnus serrulata, Myrica cerifera, Salix nigra) plant species from a contaminated stream and floodplain on the U.S. Department of Energy's Savannah River Site. Current 137 Cs levels in plants were used in conjunction with historical data to determine T e of 137 Cs in each species. Median concentrations of 137 Cs were highest in S. latifolia (0.84 Bq g -1 ) and lowest in M. cerifera (0.10 Bq g -1 ). T e 's ranged from 4.85 yr in M. cerifera to 8.35 yr in S. nigra, both terrestrial species. T e 's for all aquatic (6.30 yr) and all terrestrial (5.87) species combined were very similar. The T e 's of the two aquatic primary producers (P. punctatum and S. latifolia) in the Steel Creek ecosystem were somewhat longer than T e values previously reported for some consumers from this ecosystem

  15. Prediction of thyroidal 131I effective half-life in patients with Graves' disease.

    Science.gov (United States)

    Zhang, Ruiguo; Zhang, Guizhi; Wang, Renfei; Tan, Jian; He, Yajing; Meng, Zhaowei

    2017-10-06

    Calculation of effective thyroidal half-life (Teff) of iodine-131( 131 I) is cumbersome and tedious. The aim of this study was to investigate factors that could be used to predict Teff and to develop a Teff prediction model in Graves' disease patients. A total of 256 patients with GD were involved in this study. We investigated the influences of age, gender, disease duration, thyroid weight, antithyroid drugs, antithyroid drugs discontinuation period (ADP), thyroid function indexes, thyroid autoantibodies, thyroid-stimulating hormone receptor antibody (TRAb) level and radioactive iodine uptake (RAIU) values before 131 I therapy on Teff, applying univariate and multivariate analyses. Teff correlated negatively with thyroid peroxidase antibody, TRAb and thyroid weight, as well as positively with 24-hour, 48-hour, and 72-hour RAIU. Additionally, a longer ADP (especially≥ 14d) or without antithyroid drugs before 131 I therapy led to a longer Teff. Stepwise multiple linear regression analysis showed that 24-hour and 72-hour RAIU were statistically significant predictors of Teff ( P Graves' disease, with high prediction accuracy.

  16. Micooprecessor controlled facility for I.N.A.A. using short half life nuclides

    International Nuclear Information System (INIS)

    Bode, P.; Korthoven, P.J.M.; Bruin, M. de

    1986-01-01

    At IRI a new, fully atomated facility for short half life INAA is being developed and installed at the Institute 2 MW reactor. The fast rabbit transfer system is constructed only of plastic and carbonfiber parts, so that rabbit contamination is minimized. This system is automated in such a way that it can operate safely without direct supervision; the sequence of irradiations and measurements is optimized by a computer-program for a given set of samples and analysis procedures. The rabbit system is controlled by an Apple IIe-computer connected to the central PDP 11/44 system of the Radiochemistry department. For a given set of samples and required analysis procedures (irradiation-,decay-, and measurement times) the central computer calculates an optimal sequence of individual actions (transfer from and to the reactor, sample storage of detector) to be carried out by the system. This sequence is loaded into the Apple-computer as a series of commands together with timing information. Actual control of the procedure occurs through the peripheral computer, which makes the system independent of delays or break-downs of the central multi-user computer system. Hardware, software and operating characteristics of the fast rabbit system will be discussed. (author)

  17. Kinetic modeling and half life study on bioremediation of crude oil dispersed by Corexit 9500

    International Nuclear Information System (INIS)

    Zahed, Mohammad Ali; Aziz, Hamidi Abdul; Isa, Mohamed Hasnain; Mohajeri, Leila; Mohajeri, Soraya; Kutty, Shamsul Rahman Mohamed

    2011-01-01

    Hydrocarbon pollution in marine ecosystems occurs mainly by accidental oil spills, deliberate discharge of ballast waters from oil tankers and bilge waste discharges; causing site pollution and serious adverse effects on aquatic environments as well as human health. A large number of petroleum hydrocarbons are biodegradable, thus bioremediation has become an important method for the restoration of oil polluted areas. In this research, a series of natural attenuation, crude oil (CO) and dispersed crude oil (DCO) bioremediation experiments of artificially crude oil contaminated seawater was carried out. Bacterial consortiums were identified as Acinetobacter, Alcaligenes, Bacillus, Pseudomonas and Vibrio. First order kinetics described the biodegradation of crude oil. Under abiotic conditions, oil removal was 19.9% while a maximum of 31.8% total petroleum hydrocarbons (TPH) removal was obtained in natural attenuation experiment. All DCO bioreactors demonstrated higher and faster removal than CO bioreactors. Half life times were 28, 32, 38 and 58 days for DCO and 31, 40, 50 and 75 days for CO with oil concentrations of 100, 500, 1000 and 2000 mg/L, respectively. The effectiveness of Corexit 9500 dispersant was monitored in the 45 day study; the results indicated that it improved the crude oil biodegradation rate.

  18. Goiania radiation accident: 30 years - a half-life for a whole life..

    International Nuclear Information System (INIS)

    Reis, R.G.; Lucena, E.A.; Arantes, R.R.; Silva, A.A.; Reis, A.A.

    2017-01-01

    The radiological accident in Goiânia, Brazil, considered the largest urban radiological accident in the world, generated several publications in the technical area that are widely disseminated in the scientific literature, given the importance of the lessons learned. However, in a simple conversation with people who worked on that accident, it is noted that many reports have not been recorded. In this year in which 30 years of the event is completed, it will be of great value to record personal testimonies that are not in technical or scientific books. And what can we tell after a half-life that lasted for a lifetime? The lived stories, the situations, the improvisations, the way to solve, the overcoming, the human side, the emotions, happy or sad, short or long, funny or not. The objective of this work is to preserve, maintain and divulge reports and situations experienced by people who worked on the radiological accident with Cs-137 in Goiânia. Audio or video recordings about experiences lived in Goiânia by people who worked in that emergency situation were carried out. The reports are free and the form of registration is always at the discretion of the narrator. Storing records allows to preserve, maintain, and disclose the accident to other generations

  19. $\\beta$-decay half-life of $^{70}$Kr a bridge nuclide for the rp-process beyond A = 70

    CERN Document Server

    Oinonen, M; Jokinen, A; Baumann, P; Didierjean, François; Huck, A; Knipper, A; Ramdhane, M; Walter, G; Van Duppen, P; Huyse, M; Marguier, G; Novikov, Yu N; Popov, A; Seliverstov, D M; Schatz, H

    2000-01-01

    The $\\beta$-decay half-life of $^{70}$Kr has been measured for the first time at the ISOLDE PSB Facility at CERN. Mass separated $^{70}$Kr ions were produced by 1 GeV proton induced spallation reactions in a Nb foil. The measured half-life is 57(21) ms. This value is consistent with the half-life calculated assuming a pure Fermi decay, but is clearly lower than the value used in a recent rp-process reaction flow calculation. The result shows that the reaction flow via two-proton-capture of $^{68}$Se is 2.5 times faster than previously calculated assuming an astrophysical temperature of 1.5 GK and a density of 10$^{6}$g/cm$^{3}$.

  20. Towards a measurement of the half-life of {sup 60}Fe for stellar and early Solar System models

    Energy Technology Data Exchange (ETDEWEB)

    Ostdiek, K.; Anderson, T. [University of Notre Dame, Notre Dame, IN 46556 (United States); Bauder, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Bowers, M.; Collon, P. [University of Notre Dame, Notre Dame, IN 46556 (United States); Dressler, R. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Greene, J. [Argonne National Laboratory, 9700 South Cass Avenue, Lemont, IL 60439 (United States); Kutschera, W. [Vienna Environmental Research Accelerator Laboratory, Waehringer Strasse 17, 1090 Vienna (Austria); Lu, W. [University of Notre Dame, Notre Dame, IN 46556 (United States); Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Robertson, D. [University of Notre Dame, Notre Dame, IN 46556 (United States); Schumann, D. [Paul Scherrer Institute – Laboratory for Radiochemistry and Environmental Chemistry, 5232 Villigen (Switzerland); Skulski, M. [University of Notre Dame, Notre Dame, IN 46556 (United States); Wallner, A. [The Australian National University, Canberra, ACT 0200 (Australia)

    2015-10-15

    Radioisotopes, produced in stars and ejected into the Interstellar Medium, are important for constraining stellar and early Solar System (ESS) models. In particular, the half-life of the radioisotope, {sup 60}Fe, can have an impact on calculations for the timing for ESS events, the distance to nearby Supernovae, and the brightness of individual, non-steady-state {sup 60}Fe gamma ray sources in the Galaxy. A half-life measurement has been undertaken at the University of Notre Dame and measurements of the {sup 60}Fe/{sup 56}Fe concentration of our samples using Accelerator Mass Spectrometry has begun. This result will be coupled with an activity measurement of the isomeric decay in {sup 60}Co, which is the decay product of {sup 60}Fe. Preliminary half-life estimates of (2.53 ± 0.24) × 10{sup 6} years seem to confirm the recent measurement by Rugel et al. (2009).

  1. New evaluation of alpha decay half-life of 190Pt isotope for the Pt-Os dating system

    International Nuclear Information System (INIS)

    Tavares, O.A.P.; Medeiros, E.L.; Terranova, M.L.

    2005-08-01

    A semiempirical model based on the quantum mechanical tunnelling mechanism of alpha emission from nuclei has been used to evaluate the half-life of the Pt isotopes. For the important naturally occurring 190 Pt isotope, the radiogenic parent in the 190 Pt → 186 Os dating system, the model yielded a half-life value of (3.7± 0.3) versus 10 11 y. This is comparable to (3.2±0.1) versus 10 11 y which was obtained in the last direct counting experiment to measure the alpha activity of 190 Pt (Tavares and Terranova, Rad. Measurem. 27 (1997) 19). A literature survey of available alpha decay half-life values for 190 Pt isotope is also reported. The significant discrepancies found between data obtained by direct counting, indirect geological methods and different calculation models are analysed and discussed. (author)

  2. Examination of the biological half-life and organ d;stribution of tritiated lysin-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.

    1980-01-01

    15 μCi tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin. (L.E.)

  3. High-Precision Half-Life Measurements for the Superallowed Fermi β+ Emitters 14O and 18Ne

    Science.gov (United States)

    Laffoley, A. T.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bender, P. C.; Bidaman, H.; Bildstein, V.; Blank, B.; Bouzomita, H.; Cross, D. S.; Deng, G.; Diaz Varela, A.; Dunlop, M. R.; Dunlop, R.; Finlay, P.; Garnsworthy, A. B.; Garrett, P.; Giovinazzo, J.; Grinyer, G. F.; Grinyer, J.; Hadinia, B.; Jamieson, D. S.; Jigmeddorj, B.; Ketelhut, S.; Kisliuk, D.; Leach, K. G.; Leslie, J. R.; MacLean, A.; Miller, D.; Mills, B.; Moukaddam, M.; Radich, A. J.; Rajabali, M. M.; Rand, E. T.; Svensson, C. E.; Tardiff, E.; Thomas, J. C.; Turko, J.; Voss, P.; Unsworth, C.

    High-precision half-life measurements, at the level of ±0.04%, for the superallowed Fermi emitters 14O and 18Ne have been performed at TRIUMF's Isotope Separator and Accelerator facility. Using 3 independent detector systems, a gas-proportional counter, a fast plastic scintillator, and a high-purity germanium array, a series of direct β and γ counting measurements were performed for each of the isotopes. In the case of 14O, these measurements were made to help resolve an existing discrepancy between detection methods, whereas for 18Ne the half-life precision has been improved in anticipation of forthcoming high-precision branching ratio measurements.

  4. High-precision half-life and branching-ratio measurements for superallowed Fermi β+ emitters at TRIUMF - ISAC

    Science.gov (United States)

    Laffoley, A. T.; Dunlop, R.; Finlay, P.; Grinyer, G. F.; Andreoiu, C.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Blank, B.; Bouzomita, H.; Chagnon-Lessard, S.; Chester, A.; Cross, D. S.; Demand, G.; Diaz Varela, A.; Djongolov, M.; Ettenauer, S.; Garnsworthy, A. B.; Garrett, P. E.; Giovinazzo, J.; Glister, J.; Green, K. L.; Hackman, G.; Hadinia, B.; Jamieson, D. S.; Ketelhut, S.; Leach, K. G.; Leslie, J. R.; Pearson, C. J.; Phillips, A. A.; Rand, E. T.; Starosta, K.; Sumithrarachchi, C. S.; Svensson, C. E.; Tardiff, E. R.; Thomas, J. C.; Towner, I. S.; Triambak, S.; Unsworth, C.; Williams, S. J.; Wong, J.; Yates, S. W.; Zganjar, E. F.

    2014-03-01

    A program of high-precision half-life and branching-ratio measurements for superallowed Fermi β emitters is being carried out at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. Recent half-life measurements for the superallowed decays of 14O, 18Ne, and 26Alm, as well as branching-ratio measurements for 26Alm and 74Rb are reported. These results provide demanding tests of the Standard Model and the theoretical isospin symmetry breaking (ISB) corrections in superallowed Fermi β decays.

  5. Examination of the biological half-life and organ d; stribution of tritiated lysin-vasopressin in Brattleboro rats

    Energy Technology Data Exchange (ETDEWEB)

    Laczi, F; Laszlo, F [Szegedi Orvostudomanyi Egyetem Szeged (Hungary). 1. Belgyogyaszati Klinika; Keri, Gy; Teplan, I [Semmelweis Orvostudomanyi Egyetem, Budapest (Hungary)

    1980-04-01

    15 ..mu..Ci tritiated lysin-vasopressin (spec. act. 3.5 Ci per mmol) was administered to control and Brattleboro rats, suffering from hereditary hypothalamic diabetes insipidus. The biological half-life and the distribution of the labelled compound in the different organs were determined. The biological half-life demonstrated no significant difference, however, the vasopressin content of the small intestine was higher in the Brattleboro rats. In the other organs no significant difference was found. It can be concluded that the hereditary diabetes insipidus is not due to faster elimination of circulating vasopressin.

  6. Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-life Versus Extended Half-life Products and Those Switching from Standard Half-life to Extended Half-life Products.

    Science.gov (United States)

    Tortella, Bartholomew J; Alvir, José; McDonald, Margaret; Spurden, Dean; Fogarty, Patrick F; Chhabra, Amit; Pleil, Andreas M

    2018-01-24

    Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while

  7. The elimination half-life of benzodiazepines and fall risk: two prospective observational studies.

    Science.gov (United States)

    de Vries, Oscar J; Peeters, Geeske; Elders, Petra; Sonnenberg, Caroline; Muller, Majon; Deeg, Dorly J H; Lips, Paul

    2013-11-01

    the STOPP criteria advise against the use of long-acting benzodiazepines (LBs). to study whether LBs are associated with a higher fall risk than short-acting benzodiazepines (SBs) (elimination half-life ≤ 10 h). we used base-line data and prospective fall follow-up from the Longitudinal Aging Study Amsterdam, a longitudinal cohort study including 1,509 community-dwelling older persons (Study 1) and from a separate fall prevention study with 564 older persons after a fall (Study 2). Time to the first fall after inclusion and number of falls in the first year after inclusion were the primary endpoints. both in Study 1 and Study 2 the use of SBs was associated with time to the first fall, hazard ratio (HR) 1.62 (95% CI: 1.03-2.56) and HR 1.64 (95% CI: 1.19-2.26),respectively. LBs were not significantly associated with time to first fall, HR 1.40 (0.85-2.31) and HR 1.08 (0.72-1.62). In both studies, the use of SBs was also associated with number of falls, odds ratio (OR) 1.28 (95% CI: 1.01-1.61) and OR 1.37 (95% CI: 1.10-1.70). LBs were not significantly associated with number of falls, OR 1.23 (0.96-1.57) and 1.10 (0.82-1.48). the use of SBs is not associated with a lower fall risk compared with LBs. The use of both SBs and LBs by old persons should be strongly discouraged.

  8. Carboxyhemoglobin half-life during hyperbaric oxygen in a patient with lung dysfunction: a case report.

    Science.gov (United States)

    Weaver, Lindell K; Deru, Kayla

    2017-01-01

    The carboxyhemoglobin half-life (COHb t1/2) during hyperbaric oxygen (HBO₂) is often quoted as 23 minutes, derived from the average of two adult male volunteers breathing HBO₂ at 3 atmospheres absolute (ATA). However, the mean COHb t1/2 of 12 male volunteer smokers was 26.3 minutes at 1.58 ATA and in 12 non-intubated carbon monoxide (CO) poisoned patients treated at 3 ATA, was 43 minutes. An 81-year old male, poisoned by an improperly ventilated natural gas heater, was intubated for coma, then treated with HBO₂. His PaO₂/FiO₂ = 283 from aspiration. His initial COHb was 34.4%, and 18 minutes before HBO₂, 5.9%. After a compression interval of 17 minutes, the COHb measured after 22 minutes at 3 ATA was 3.3%. By exponential decay, his COHb t1/2 before HBO₂ was 95 minutes. We estimate the range for COHb t1/2 during compression as 62-81 minutes and for the 3-ATA interval, 58 to 49 minutes, respectively. The mid-point estimate of COHb t1/2 at 3 ATA was 53 minutes. The COHb t1/2 we calculated is greater than previously reported, but longer in our patient possibly because of concomitant respiratory failure, lung dysfunction, and mechanical ventilation. The often-cited COHb t1/2 of 23 minutes, likely underestimates the actual COHb t1/2 in CO-poisoned patients, especially those with cardiopulmonary dysfunction.

  9. Half-life and mass measurement of the short-lived {sup 215}Po isotope (1.78 ms) at the FRS ion catcher

    Energy Technology Data Exchange (ETDEWEB)

    Rink, Ann-Kathrin; Bergmann, Julian; Ebert, Jens; Hornung, Christine; Miskun, Ivan; Reiter, Moritz P. [Justus-Liebig Universitaet Giessen (Germany); Ayet San Andres, Samuel; Dickel, Timo; Plass, Wolfgang R.; Scheidenberger, Christoph [Justus-Liebig Universitaet Giessen (Germany); GSI, Darmstadt (Germany); Geissel, Hans; Purushothaman, Sivaji [GSI, Darmstadt (Germany)

    2016-07-01

    At the Low-Energy Branch (LEB) of the Super-FRS at FAIR, precision experiments with exotic nuclei will be performed using ion traps and lasers. The nuclei will be produced at relativistic energies, slowed down, thermalised in a cryogenic stopping cell (CSC) and made available to various experiments. The thermalisation is a challenging task because of the large energy straggling of the nuclei after production, which requires a stopping cell with large areal densities. Also, the process needs to be performed on a millisecond time scale in order to give access to short-lived nuclides. This method has already been successfully applied at the FRS Ion Catcher at GSI using a prototype CSC. Recently the potential of the method has been demonstrated by the mass and half-life measurement of the {sup 215}Po nuclide with a half-life of 1.78 ms only. The multiple-reflection time-of-flight mass spectrometer at the FRS Ion Catcher has been used to determine the mass to a sub-ppm accuracy and to provide a mass-selected beam for alpha spectroscopy. Furthermore, experiments have been performed with the prototype CSC in order to test novel concepts to be used with the final version of the CSC for the LEB.

  10. Biological half-life of bromide in the rat depends primarily on the magnitude of sodium intake

    Czech Academy of Sciences Publication Activity Database

    Pavelka, Stanislav; Babický, Arnošt; Vobecký, Miloslav

    2005-01-01

    Roč. 54, č. 6 (2005), s. 639-644 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50110509 Keywords : biological half-life * bromide * sodium Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

  11. High-precision half-life measurements of the T =1 /2 mirror β decays 17F and 33Cl

    Science.gov (United States)

    Grinyer, J.; Grinyer, G. F.; Babo, M.; Bouzomita, H.; Chauveau, P.; Delahaye, P.; Dubois, M.; Frigot, R.; Jardin, P.; Leboucher, C.; Maunoury, L.; Seiffert, C.; Thomas, J. C.; Traykov, E.

    2015-10-01

    Background: Measurements of the f t values for T =1 /2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the f t values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T =1 /2 β+ emitters, 17F and 33Cl, in order to eliminate the half-life as the leading source of uncertainty in their f t values. Method: Half-lives of 17F and 33Cl were determined using β counting of implanted radioactive ion beam samples on a moving tape transport system at the Système de Production d'Ions Radioactifs Accélérés en Ligne low-energy identification station at the Grand Accélérateur National d'Ions Lourds. Results: The 17F half-life result, 64.347 (35) s, precise to ±0.05 % , is a factor of 5 times more precise than the previous world average. The half-life of 33Cl was determined to be 2.5038 (22) s. The current precision of ±0.09 % is nearly 2 times more precise compared to the previous world average. Conclusions: The precision achieved during the present measurements implies that the half-life no longer dominates the uncertainty of the f t values for both T =1 /2 mirror decays 17F and 33Cl.

  12. Comparison of isotope dilution and excretion methods for determining the half-life of ascorbic acid in the guinea pig

    International Nuclear Information System (INIS)

    Kipp, D.E.; Rivers, J.M.

    1984-01-01

    The half-life of ascorbic acid (AA) in guinea pigs was investigated by the isotope dilution and excretion methods. The dilution method measures [1-14C]AA disappearance from the plasma, whereas the excretion method measures the elimination of [1-14C]AA and the metabolites from the body. Two groups of animals underwent both isotope studies in reverse order. Animals were conditioned to the experimental procedures and fed 2.5 mg AA/100 g body weight orally to maintain a daily intake of the vitamin independent of food consumption. The two isotope procedures imposed similar stress on the animals, as determined by plasma cortisol levels and body weight changes. The AA half-life calculations of the rapidly exchangeable pool by the isotope dilution method yielded values of 1.23 and 0.34 hours for the two groups, respectively. The half-life of the slowly exchangeable pool for the two groups was 60.2 and 65.8 hours, respectively. The half-life of AA in the rapidly exchangeable pool, as measured by the excretion studies, was 4.57-8.75 hours. For the slowly exchangeable pool, it was 146-149 hours. The longer half-life of both pools obtained with the excretion method indicates that the isotope is disappearing from the plasma more rapidly than it is being excreted. This suggests that a portion of the [1-14C]AA leaving the plasma is removed to a body pool that is not sampled by the isotope excretion method

  13. Effective Half-Life of Caesium-137 in Various Environmental Media at the Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Paller, M. H.; Jannik, G. T.; Baker, R. A.

    2014-05-01

    During the operational history of the Savannah River Site (SRS), many different radionuclides have been released from site facilities into the SRS environment. However, only a relatively small number of pathways, most importantly 137Cs in fish and deer, have contributed significantly to doses and risks to the public. The “effective” half-lives (Te) of 137Cs (which include both physical decay and environmental dispersion) in Savannah River floodplain soil and vegetation and in fish and white-tailed deer from the SRS were estimated using long-term monitoring data. For 1974–2011, the Tes of 137Cs in Savannah River floodplain soil and vegetation were 17.0 years (95% CI = 14.2–19.9) and 13.4 years (95% CI = 10.8–16.0), respectively. These Tes were greater than in a previous study that used data collected only through 2005 as a likely result of changes in the flood regime of the Savannah River. Field analyses of 137Cs concentrations in deer collected during yearly controlled hunts at the SRS indicated an overall Te of 15.9 years (95% CI = 12.3–19.6) for 1965–2011; however, the Te for 1990–2011 was significantly shorter (11.8 years, 95% CI = 4.8–18.8) due to an increase in the rate of 137Cs removal. The shortest Tes were for fish in SRS streams and the Savannah River (3.5–9.0 years), where dilution and dispersal resulted in rapid 137Cs removal. Long-term data show that Tes are significantly shorter than the physical half-life of 137Cs in the SRS environment but that they can change over time. Therefore, it is desirable have a long period of record for calculating Tes and risky to extrapolate Tes beyond this period unless the processes governing 137Cs removal are clearly understood.

  14. Coronavirus infection of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Horzinek, M C; Rottier, P J

    1995-01-01

    Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

  15. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  16. Study on the biological half-life and organ-distribution of tritiated lysine-vasopressin in Brattleboro rats

    International Nuclear Information System (INIS)

    Laczi, F.; Laszlo, F.A.; Keri, Gy.; Teplan, I.

    1980-01-01

    The biological half-life and organ-distribution of tritiated lysine-vasopressin were determined in R-Amsterdam rats, and in homozygous and heterozygous Brattleboro rats with hereditary central diabetes insipidus. It was found that the biological half-life of the tritiated lysin-vasopressin in the Brattleboro rats did not differ significantly from that found in the R-Amsterdam rats. The highest radioactivities were observed in the neuro- and adenohypophyses and in the kidneys of both the R-Amsterdam and the Brattleboro rats. The accumulation of tritiated LVP was higher in the small intestine of the Brattleboro rats than in that of the R-Amsterdam animals. The results have led to the conclusion that the accelerated elimination of vasopressin and its pathologic organ-accumulation are probably not involved in the water metabolism disturbance of Brattleboro rats with hereditary hypothalamic diabetes insipidus. (author)

  17. Improved half-life determination and β-delayed γ-ray spectroscopy for 18Ne decay

    Science.gov (United States)

    Grinyer, G. F.; Ball, G. C.; Bouzomita, H.; Ettenauer, S.; Finlay, P.; Garnsworthy, A. B.; Garrett, P. E.; Green, K. L.; Hackman, G.; Leslie, J. R.; Pearson, C. J.; Rand, E. T.; Sumithrarachchi, C. S.; Svensson, C. E.; Thomas, J. C.; Triambak, S.; Williams, S. J.

    2013-04-01

    The half-life of the superallowed Fermi β+ emitter 18Ne has been determined to ±0.07% precision by counting 1042 keV delayed γ rays that follow approximately 8% of all β decays. The deduced half-life, T1/2=1.6648(11) s, includes a 0.7% correction that accounts for systematic losses associated with rate-dependent detector pulse pileup that was determined using a recently developed γ-ray photopeak-counting technique. This result is a factor of two times more precise than, and in excellent agreement with, a previous lower-statistics measurement that employed the same experimental setup. High-resolution β-delayed γ-ray spectroscopy results for the relative γ-ray intensities and β-decay branching ratios to excited states in the daughter 18F are also presented.

  18. Measurement of the two neutrino double beta decay half-life of Zr-96 with the NEMO-3 detector

    Energy Technology Data Exchange (ETDEWEB)

    Argyriades, J. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Arnold, R. [IPHC, Universite de Strasbourg, CNRS/IN2P3, F-67037 Strasbourg (France); Augier, C. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Baker, J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Barabash, A.S. [ITEP, Institute of Theoretical and Experimental Physics, 117259 Moscow (Russian Federation); Basharina-Freshville, A. [University College London, WC1E 6BT London (United Kingdom); Bongrand, M. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France); Broudin-Bay, G. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Brudanin, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Caffrey, A.J. [INL, Idaho National Laboratory, 83415 Idaho Falls (United States); Chapon, A. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Chauveau, E. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Daraktchieva, Z. [University College London, WC1E 6BT London (United Kingdom); Durand, D. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Egorov, V. [JINR, Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation); Fatemi-Ghomi, N. [University of Manchester, M13 9PL Manchester (United Kingdom); Flack, R. [University College London, WC1E 6BT London (United Kingdom); Guillon, B. [LPC, ENSICAEN, Universite de Caen, CNRS/IN2P3, F-14032 Caen (France); Hubert, Ph. [Universite Bordeaux, CENBG, UMR 5797, F-33175 Gradignan (France); CNRS/IN2P3, Centre d' Etudes Nucleaires de Bordeaux Gradignan, UMR5797, F-33175 Gradignan (France); Jullian, S. [LAL, Universite Paris-Sud 11, CNRS/IN2P3, F-91405 Orsay (France)

    2010-12-08

    Using 9.4 g of {sup 96}Zr isotope and 1221 days of data from the NEMO-3 detector corresponding to 0.031 kg y, the obtained 2{nu}{beta}{beta} decay half-life measurement is T{sub 1/2}{sup 2{nu}=}[2.35{+-}0.14(stat){+-}0.16(syst)]x10{sup 19} yr. Different characteristics of the final state electrons have been studied, such as the energy sum, individual electron energy, and angular distribution. The 2{nu} nuclear matrix element is extracted using the measured 2{nu}{beta}{beta} half-life and is M{sup 2{nu}=}0.049{+-}0.002. Constraints on 0{nu}{beta}{beta} decay have also been set.

  19. Near-optimum procedure for half-life measurement by high-resolution gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Parker, J.L.

    1989-01-01

    A near-optimum procedure for using high-resolution γ-ray spectrometry to measure the half-lives of appropriate γ-ray- emitting-nuclides is presented. Among the important points of the procedure are the employment of the reference source method for implicit correction of pileup and deadtime losses; the use of full-energy peak-area ratios as the fundamental measured quantities; and continuous, high-rate data acquisition to obtain good results in a fraction of a half-life if desired. Equations are given for estimating the precision of the computed half-lives in terms of total measurement time, number of spectral acquisitions, and the precision of peak-area ratios. Results of 169 Yb half-life measurements are given as an example of the procedure's application. 3 refs., 2 tabs

  20. Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma.

    Science.gov (United States)

    Ito, Katsuki; Hibi, Kenji; Ando, Hideyuki; Hidemura, Kazuhiko; Yamazaki, Taiji; Akiyama, Seiji; Nakao, Akimasa

    2002-02-01

    Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p Clearance (k) showed a significant difference between the groups (p time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.

  1. Absorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant origin

    International Nuclear Information System (INIS)

    Johnson, P.E.; Lykken, G.I.; Korynta, E.D.

    1991-01-01

    Absorption and biological half-life of 54 Mn were measured in adult men and women fed foods labeled intrinsically or extrinsically with 54 Mn. Each subject consumed a series of three test meals consisting of a food labeled intrinsically, a food labeled extrinsically or MnCl 2 (control) served in random order. The foods tested were lettuce, spinach, wheat and sunflower seeds. Lettuce meals and their controls contained 9.65 mumol Mn; other meals contained 22.50 mumol Mn. In addition to the test food or MnCl 2 , each meal consisted of vegetable oil (5 g), salt (NaCl, 0.15 g) and crackers (10 g), which provided 0.55 mumol Mn. There were no differences in percentage of Mn absorption or biological half-life of 54 Mn for any of the intrinsically/extrinsically labeled food pairs. Absorption of 54 Mn from MnCl 2 (8.90%) was greater than from lettuce (5.20%), spinach (3.81%), wheat (2.16%) or sunflower seeds (1.71%), but the biological half-life did not vary with the source of Mn. Absorption of 54 Mn from lettuce was significantly (P less than 0.05) greater than from wheat or sunflower seeds. Although the Mn dose in the test meal was less for lettuce than for the other foods, there was no difference in Mn absorption from MnCl 2 between the subjects fed lettuce and subjects fed other foods. There was no correlation of either 54 Mn absorption or biological half-life with whole blood or plasma Mn

  2. On the way to high-power linear proton accelerator for the long half-life radionuclides transmutation

    International Nuclear Information System (INIS)

    Batskikh, G.I.; Lupandin, O.S.; Murin, B.P.; Fedotov, A.P.

    1991-01-01

    The concept of continuous mode high-power linear proton accelerator with 1.5 GeV energy, 0.3 A current for the long half-life nuclides transmutation into the short ones (waste of atomic power plants (APP)) is proposed. The accelerator design main principles, scheme and parameters are presented. The accent is made on the accelerator efficiency, reliability and radiation purity. (author)

  3. On the statistical evaluation of inconsistent measurement results illustrated on the example of the 90Sr half-life

    International Nuclear Information System (INIS)

    Zijp, W.L.

    1985-12-01

    The problem how to make an objective evaluation of inconsistent numerical observations made by different authors or laboratories on the same physical quantity is dealt with. The problem is treated in a practical way in the light of the example on the half-life of 90 Sr, and it is to some extent a response to a document by Gray (1985) on the same topic

  4. The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life.

    Directory of Open Access Journals (Sweden)

    Yu-Hang Zhang

    Full Text Available A drug's biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347, monoamine transmembrane transporter activity (GO:0008504, negative regulation of synaptic transmission (GO:0050805, neuroactive ligand-receptor interaction (hsa04080, serotonergic synapse (hsa04726, and linoleic acid metabolism (hsa00591, among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

  5. Influence of antithyroid medication on effective half-life and uptake of 131 I following radioiodine therapy

    International Nuclear Information System (INIS)

    Moka, D.; Voth, E.; Schicha, H.

    1997-01-01

    Aim: A radioiodine therapy (RIT) in thyrotoxic patients receiving antithyroid drugs (ATD) leads in comparison to nonpretreated patients either to higher therapeutic doses or to higher treatment failure rates. Aim of this study was to optimize the effect of RIT in patients pretreated with ATD. Methods: Therefore, the influence of ATD was assessed in 109 patients with shortened effective half-life of 131 I. RIT was performed under stationary conditions. Radioiodine activity of the thyroid gland was stopped three days after RIT. The patients antithyroid medication was stopped three days after RIT. The progress of the first RIT and of a second radioiodine application, which still was necessary in 29 patients, was compared to 32 patients receiving ATD, continuously. Results: Values of effective half-life for 131 I rose significantly from 3.2±0.2 to 5.7±0.2 days (Graves' disease: 3.4 to 5.7 days; toxic goiters' disease: Multifocal autonomy 3.2 to 6.2 days; unifocal autonomy 2.5 auf 5.0 days) 2-3 days after stopping ATD. There was an increase of the 131 I-uptake of a second RIT decreased significantly in patients receiving ATD, continuously. Conclusion: Effective half-life and uptake of 131 I was affected significantly by ATD. The stop taking of ATD after RIT is useful to improve an apparent insufficient RIT in thyrotoxic patients receiving ATD. (orig.) [de

  6. Thirty years after Chernobyl: Long-term determination of 137Cs effective half-life in the lichen Stereocaulon vesuvianum.

    Science.gov (United States)

    Savino, F; Pugliese, M; Quarto, M; Adamo, P; Loffredo, F; De Cicco, F; Roca, V

    2017-06-01

    It has been widely shown that nuclear fallout includes substances, which accumulate in organisms such as crustaceans, fish, mushrooms and lichens, helping to evaluate the activity concentration of contaminants accumulated on a long time. In this context, radiocaesium deposited in soil following the Chernobyl accident on 26 April 1986 is known to have remained persistently available for plant uptake in many areas of Europe. Studies on the lichen Stereocaulon vesuvianum show the plant's high capacity to retain radionuclides from the substrate and the air. After the Chernobyl accident, starting from September 1986, at the Radioactivity Laboratory (LaRa) of the University of Naples Federico II, four monitoring campaigns to evaluate the activity concentration of four isotopes of the two elements caesium and ruthenium ( 134 Cs, 137 Cs, 103 Ru and 106 Ru) were carried out until 1999. This study allowed the effective half-life of 134 Cs and 137 Cs to be estimated. Twenty-eight years after the accident, in December 2014, a further sampling was carried out; only 137 Cs was revealed beyond the detection limits, measuring activity concentrations ranging from 20 to 40 Bq/kg, while the other radionuclides were no longer observed due to their shorter half-life. The last sampling allowed more precise determination of the effective half-life of 137 Cs (6.2 ± 0.1 year), due to the larger dataset on a large time period. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Efferocytosis of Pathogen-Infected Cells

    Directory of Open Access Journals (Sweden)

    Niloofar Karaji

    2017-12-01

    Full Text Available The prompt and efficient clearance of unwanted and abnormal cells by phagocytes is termed efferocytosis and is crucial for organism development, maintenance of tissue homeostasis, and regulation of the immune system. Dying cells are recognized by phagocytes through pathways initiated via “find me” signals, recognition via “eat me” signals and down-modulation of regulatory “don’t eat me” signals. Pathogen infection may trigger cell death that drives phagocytic clearance in an immunologically silent, or pro-inflammatory manner, depending on the mode of cell death. In many cases, efferocytosis is a mechanism for eliminating pathogens and pathogen-infected cells; however, some pathogens have subverted this process and use efferocytic mechanisms to avoid innate immune detection and assist phagocyte infection. In parallel, phagocytes can integrate signals received from infected dying cells to elicit the most appropriate effector response against the infecting pathogen. This review focuses on pathogen-induced cell death signals that drive infected cell recognition and uptake by phagocytes, and the outcomes for the infected target cell, the phagocyte, the pathogen and the host.

  8. Dendritic cells during Epstein Barr virus infection

    Directory of Open Access Journals (Sweden)

    Christian eMunz

    2014-06-01

    Full Text Available Epstein Barr virus (EBV causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This -herpesvirus infects primarily human B and epithelial cells, but has been reported to be sensed by dendritic cells (DCs during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV specific vaccine development will be discussed in this review.

  9. Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

    International Nuclear Information System (INIS)

    Oliveira, P. A.; Santos, J. A. M.

    2014-01-01

    Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as 99m Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a careful analysis of the methodology, for the case of 99m Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using 99m Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for 99m Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides

  10. Phenobarbital administration every eight hours: improvement of seizure management in idiopathic epileptic dogs with decreased phenobarbital elimination half-life.

    Science.gov (United States)

    Stabile, F; Barnett, C R; De Risio, L

    2017-02-18

    Estimated prevalence of canine idiopathic epilepsy is 0.6 per cent in the first-opinion canine population in the UK. Phenobarbital monotherapy has been reported to reduce/eradicate seizure activity in 60-93 per cent of idiopathic epileptic dogs (IEDs). The objective of this study was to evaluate safety and efficacy of the administration of phenobarbital orally every eight hours in IEDs with phenobarbital elimination half-life less than 20 hours. Medical records of 10 IEDs in which steady state trough serum phenobarbital levels were within the reference range and phenobarbital elimination half-life had become less than 20 hours following prolonged administration every 12 hours were reviewed. Side effects and seizure frequency when phenobarbital was administered every 12 hours or 8 hours were compared. In all dogs the side effects of the antiepileptic medication treatment improved. When phenobarbital was administered every eight hours, 9/10 dogs experienced improvement in seizure frequency and 8/10 dogs maintained seizure freedom for a period three times longer than the longest interictal interval period previously recorded. Reduction in the severity and number of clusters of seizures was recorded in one of the remaining two dogs. The administration of phenobarbital orally every eight hours in IEDs with decreased phenobarbital elimination half-life appears safe and can improve seizure management. The results of this study were presented in abstract form (poster) for the 28th symposium of the European Society of Veterinary Neurology - European College of Veterinary Neurology (ESVN), September 18-19, 2015, Amsterdam, Netherlands. British Veterinary Association.

  11. Murid herpesvirus-4 exploits dendritic cells to infect B cells.

    Directory of Open Access Journals (Sweden)

    Miguel Gaspar

    2011-11-01

    Full Text Available Dendritic cells (DCs play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4, infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells.

  12. High-precision measurement of the 19Ne half-life and implications for right-handed weak currents.

    Science.gov (United States)

    Triambak, S; Finlay, P; Sumithrarachchi, C S; Hackman, G; Ball, G C; Garrett, P E; Svensson, C E; Cross, D S; Garnsworthy, A B; Kshetri, R; Orce, J N; Pearson, M R; Tardiff, E R; Al-Falou, H; Austin, R A E; Churchman, R; Djongolov, M K; D'Entremont, R; Kierans, C; Milovanovic, L; O'Hagan, S; Reeve, S; Sjue, S K L; Williams, S J

    2012-07-27

    We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

  13. Vitamin E plasma kinetics in swine show low bioavailability and short half-life of -α-tocopheryl acetate.

    Science.gov (United States)

    van Kempen, T A T G; Reijersen, M H; de Bruijn, C; De Smet, S; Michiels, J; Traber, M G; Lauridsen, C

    2016-10-01

    Vitamin E is important for animal production because of its effects on health and product quality, but the amount and form required remains controversial. Our objective was to quantify the absolute bioavailability of oral -α-tocopheryl acetate (α-TAc) in swine (22 ± 1 kg and 8 wk old, fitted with jugular catheters) adapted to a diet supplemented with 75 mg/kg -α-TAc; 75 mg/kg was chosen because this level represents the nonweighted average inclusion level in piglet diets across Western key swine-producing countries. For this, a 350-g test meal (6% fat) was supplied at time 0 containing 75 mg deuterated (D9) -α-TAc to 9 animals, and 8 animals received an intravenous () dose containing deuterated (D6) RRR-α-tocopherol (α-T) at one-eighth the oral dose and a test meal without supplemental vitamin E. Plasma samples (12 to 13 per animal) were obtained at incremental intervals over 75 h for analysis of deuterated α-T using liquid chromatography-tandem mass spectrometry. Surprisingly, the i.v. dose rapidly disappeared from plasma and then reappeared. The half-life for this first peak was only 1.7 ± 0.3 min. The second peak had an appearance rate (Ka) of 0.10 ± 0.06 d and a half-life of 5.9 ± 1.2 h. Oral dosing resulted, after a lag of 56 min, in a Ka of 0.91 ± 0.21 d and a half-life of 2.6 ± 0.8 h. The bioavailability for oral α-TAc was 12.5%, whereas the area under the curve was only 5.4%. This low bioavailability, small area under the curve, and short half-life are likely because of various factors, that is, the use of only 6% fat in the diet, the use of the acetate ester and , and the high dose relative to requirements. In conclusion, i.v. dosed vitamin E shows both a rapid and a very slow pool, whereas orally dosed vitamin E shows a single slow pool. The oral material has a very short half-live (44% of i.v. or 2.6 h), low bioavailability (12.5%), and a very small area under the curve (5.4%), bringing into question the efficacy of typical doses of vitamin

  14. A Half-Life Measurement of the 343.4 keV Level in {sup 175}Lu

    Energy Technology Data Exchange (ETDEWEB)

    Hoejeberg, M; Malmskog, S G

    1969-05-15

    Great theoretical interest has recently been shown in the asymptotically forbidden 5/2 5/2+ [402] - 7/2 7/2+ [404] M1-transitions in {sup 181}Ta and {sup 175}Lu . Half-lives of the 5/2 5/2+ [402] level in {sup 175}Lu have been reported which differ by more than a factor of 10. Using an electron-electron coincidence spectrometer the half-life of this level has been re-measured and a value of (0.26 {+-} 0.02) nsec has been established.

  15. Biological half-life and distribution of radiocesium in a contaminated population of green treefrogs Hyla cinerea

    International Nuclear Information System (INIS)

    Dapson, R.W.; Kaplan, L.

    1975-01-01

    Radiocesium content of adult male green treefrogs Hyla cinerea from a contaminated habitat is adequately described by a log normal distribution with mean 2.277 log 10 pCi g -1 dry wt (189.2 pCi g -1 ) and variance of 0.031. There was significant negative correlation of body burden with body length and weight (p 2 = 0.10). Biological half-life of radiocesium in unfed, captive frogs held at 20 deg - 30 deg C averaged 30.1 d. (author)

  16. High-Precision Measurement of the Ne19 Half-Life and Implications for Right-Handed Weak Currents

    Science.gov (United States)

    Triambak, S.; Finlay, P.; Sumithrarachchi, C. S.; Hackman, G.; Ball, G. C.; Garrett, P. E.; Svensson, C. E.; Cross, D. S.; Garnsworthy, A. B.; Kshetri, R.; Orce, J. N.; Pearson, M. R.; Tardiff, E. R.; Al-Falou, H.; Austin, R. A. E.; Churchman, R.; Djongolov, M. K.; D'Entremont, R.; Kierans, C.; Milovanovic, L.; O'Hagan, S.; Reeve, S.; Sjue, S. K. L.; Williams, S. J.

    2012-07-01

    We report a precise determination of the Ne19 half-life to be T1/2=17.262±0.007s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

  17. The effective and environmental half-life of 137Cs at Coral Islands at the former US nuclear test site

    International Nuclear Information System (INIS)

    Robison, William L.; Conrado, Cynthia L.; Bogen, Kenneth T.; Stoker, A. Carol

    2003-01-01

    The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 ( 137 Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of 137 Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of 137 Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of 137 Cs and 90 Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of 137 Cs and 90 Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of 137 Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the 137 Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the 137 Cs/ 90 Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the 137 Cs/ 90 Sr ratios in soil in 1987 relative to the 137 Cs/ 90 Sr ratios at the time of deposition in 1954 is less than 17 years. The magnitude of the decrease below 17 years depends on

  18. The effective and environmental half-life of 137Cs at Coral Islands at the former US nuclear test site.

    Science.gov (United States)

    Robison, William L; Conrado, Cynthia L; Bogen, Kenneth T; Stoker, A Carol

    2003-01-01

    The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 (137Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of 137Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of 137Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of 137Cs and 90Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of 137Cs and 90Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of 137Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the 137Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the 137Cs/90Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the 137Cs/90Sr ratios in soil in 1987 relative to the 137Cs/90Sr ratios at the time of deposition in 1954 is less than 17 years. The magnitude of the decrease below 17 years depends on the ELH for 90Sr

  19. Fungal cell gigantism during mammalian infection.

    Directory of Open Access Journals (Sweden)

    Oscar Zaragoza

    2010-06-01

    Full Text Available The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  20. Fungal cell gigantism during mammalian infection.

    Science.gov (United States)

    Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

    2010-06-17

    The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  1. Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

    Science.gov (United States)

    Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D; Heywood, Sam; Humphreys, David P

    2016-10-01

    An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG.

  2. Ultra-High Precision Half-Life Measurement for the Superallowed &+circ; Emitter ^26Al^m

    Science.gov (United States)

    Finlay, P.; Demand, G.; Garrett, P. E.; Leach, K. G.; Phillips, A. A.; Sumithrarachchi, C. S.; Svensson, C. E.; Triambak, S.; Grinyer, G. F.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Williams, S. J.

    2009-10-01

    The calculated nuclear structure dependent correction for ^26Al^m (δC-δNS= 0.305(27)% [1]) is smaller by nearly a factor of two than the other twelve precision superallowed cases, making it an ideal case to pursue a reduction in the experimental errors contributing to the Ft value. An ultra-high precision half-life measurement for the superallowed &+circ; emitter ^26Al^m has been made at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, Canada. A beam of ˜10^5 ^26Al^m/s was delivered in October 2007 and its decay was observed using a 4π continuous gas flow proportional counter as part of an ongoing experimental program in superallowed Fermi β decay studies. With a statistical precision of ˜0.008%, the present work represents the single most precise measurement of any superallowed half-life to date. [4pt] [1] I.S. Towner and J.C. Hardy, Phys. Rev. C 79, 055502 (2009).

  3. High-Precision Half-Life and Branching Ratio Measurements for the Superallowed β+ Emitter 26Alm

    Science.gov (United States)

    Finlay, P.; Svensson, C. E.; Demand, G. A.; Garrett, P. E.; Green, K. L.; Leach, K. G.; Phillips, A. A.; Rand, E. T.; Ball, G.; Bandyopadhyay, D.; Djongolov, M.; Ettenauer, S.; Hackman, G.; Pearson, C. J.; Leslie, J. R.; Andreoiu, C.; Cross, D.; Austin, R. A. E.; Grinyer, G. F.; Sumithrarachchi, C. S.; Williams, S. J.; Triambak, S.

    2013-03-01

    High-precision half-life and branching-ratio measurements for the superallowed β+ emitter 26Alm were performed at the TRIUMF-ISAC radioactive ion beam facility. An upper limit of ≤ 15 ppm at 90% C.L. was determined for the sum of all possible non-analogue β+/EC decay branches of 26Alm, yielding a superallowed branching ratio of 100.0000+0-0.0015%. A value of T1/2 = 6:34654(76) s was determined for the 26Alm half-life which is consistent with, but 2.5 times more precise than, the previous world average. Combining these results with world-average measurements yields an ft value of 3037.58(60) s, the most precisely determined for any superallowed emitting nucleus to date. This high-precision ft value for 26Alm provides a new benchmark to refine theoretical models of isospin-symmetry-breaking effects in superallowed β decays.

  4. RBC-/Cr-51/ half-life and albumin turnover in growing Beagle dogs during chronic radial acceleration

    Science.gov (United States)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1979-01-01

    The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control of animals. Albumin-(I-125) and autologous RBC-(Cr-51) preparations were injected into all dogs at day 82 of the centrifugation periods, and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifugated groups, one with a normal half-life of 27 + or - 1 S.E.M. d, and one with a significantly (p less than 0.01) shorter half-life of 15 + or - 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as-yet unknown mechanism to affect RBC population kinetics.

  5. An improved method for determination of technetium-99m half-life for the quality assurance procedures of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Abd Jalil Abd Hamid; Juhari Mohd Yusof; Zakaria Ibrahim; Wan Mohd Ferdaus Wan Ishak; Mohamad Hafiz Ahmad

    2009-01-01

    An improve method for identity tests of technetium-99m for the quality assurance procedures are presented. Computerized methods based on the least-squares of decay curve fitting for half-life estimation of technetium-99m was tested. Thus, least-squares method was employ as a decay curve fitting procedures in our software. Theoretical calculated half-life of technetium-99m for evaluation was performed for comparison. In Fig. 3 is shown, the decay curve fitting of a sample over one second counting time interval. The R2 value of the curve suggests that the time of the study was too short to obtain acceptable value. A similar measurement for another data set was done for a longer period of time and in Table 1 is shown a representative decay curve fitting. The value was found to be 6.006 hours with a discrepancy of -0.28% from the value taken from the literature. The value is in agreement with the literature for time interval greater than 2 seconds. The results obtained by this method show that the used of least-squares method for decay curve fitting are appropriate for routine identity tests. This confirmed that the least-squares method applied in our decay curve fitting software are remarkably improved and convenient for routine identity tests purposes. (Author)

  6. Determination of short half-life elements in biological, foodstuff, and environmental samples qualitatively by neutron activation analysis

    International Nuclear Information System (INIS)

    Syukria Kurniawati; Muhayatun Santoso; Diah Dwiana Lestiani

    2010-01-01

    NAA applications at routine operation power of 15 MW at Multipurpose Reactor GA Siwabessy (MPR-GAS) for sample matrices analysis have been widely applied. However, the results are not optimum for some matrices especially for short half-live elements. Preliminary study of short half-life elements determination in biological, foodstuff, and environmental samples using 1 MW power have been conducted to solve this problem. The samples were irradiated in rabbit system of MPR-GAS for 5 minutes, counted for 200 seconds by HPGe detector, and the spectrum were analyzed further using software Genie 2000 and Bandung NAA Utility. Analysis under 1 MW power on biological and foodstuff samples were capable to detect eight elements: Al, Br, CI, Ca, I, K, Mg, Ti, and Na for biological samples; Al, Br, CI, Ca, I, K, Mg, Mn, and Na for foodstuff samples, while at 15 MW power only three elements (CI, K, Na) were detected. At 1 MW power the counting process is more optimum due to smaller radiation exposure and dead time. For the environmental samples, the number of elements detected by 1 MW and 15 MW powers did not differ significantly. Generally, the results on the three types of samples showed that the elements of short half-life are better detected at 1 MW than that of 15 MW power. Further research needs to be done to obtain the optimum analytical conditions for irradiation and counting time determination. (author)

  7. Relationship between isotope half-life and prostatic edema for optimal prostate dose coverage in permanent seed implants

    International Nuclear Information System (INIS)

    Villeneuve, Maxime; Leclerc, Ghyslain; Lessard, Etienne; Pouliot, Jean; Beaulieu, Luc

    2008-01-01

    The robustness of treatment planning to prostatic edema for three different isotopes ( 125 I, 103 Pd, and 131 Cs) is explored using dynamical dose calculations on 25 different clinical prostate cases. The treatment plans were made using the inverse planning by simulated annealing (IPSA) algorithm. The prescription was 144, 127, and 125 Gy for 125 I, 131 Cs, and 103 Pd, respectively. For each isotope, three dose distribution schemes were used to impose different protection levels to the urethra: V 120 =0%, V 150 =0%, and V 150 =30%. Eleven initial edema values were considered ranging from 1.0 (no edema) to 2.0 (100%). The edema was assumed to resolve exponentially with time. The prostate volume, seed positions, and seed activity were dynamically tracked to produce the final dose distribution. Edema decay half-lives of 10, 30, and 50 days were used. A total of 675 dynamical calculations were performed for each initial edema value. For the 125 I isotope, limiting the urethra V 120 to 0% leads to a prostate D 90 under 140 Gy for initial edema values above 1.5. Planning with urethra V 150 at 0% provides a good response to the edema; the prostate D 90 remains higher than 140 Gy for edema values up to 1.8 and a half-life of 30 days or less. For 103 Pd, the prostate D 90 is under 97% of the prescription dose for approximately 66%, 40%, and 30% of edema values for urethra V 120 =0%, V 150 =0%, and V 150 =30%, respectively. Similar behavior is seen for 131 Cs and the center of the prostate becomes 'cold' for almost all edema scenarios. The magnitude of the edema following prostate brachytherapy, as well as the half-life of the isotope used and that of the edema resorption, all have important impacts on the dose distribution. The 125 I isotope with its longer half-life is more robust to prostatic edema. Setting up good planning objectives can provide an adequate compromise between organ doses and robustness. This is even more important since seed misplacements will contribute

  8. Direct Deposition Effect on the Distribution of Radiocesium in Persimmon Trees and the Effective Half-life

    Energy Technology Data Exchange (ETDEWEB)

    Tagami, Keiko; Uchida, Shigeo [National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-7444 (Japan)

    2014-07-01

    Radiocesium ({sup 137}Cs) concentrations in persimmon tree tissues collected at Chiba, about 220 km south from Fukushima Daiichi nuclear power plant (FDNPP), were measured to obtain half-life of radiocesium in the trees. Persimmon (Diospyros kaki) is a deciduous tree and bears edible fruits in autumn. There were no leaves when the sampling area was received the radioactive fallout in March 2011 due to the FDNPP accident; the amount of {sup 137}Cs radioactivity in this area was ca. 13 kBq/m{sup 3} Both {sup 137}Cs and {sup 134}Cs were found in the newly emerged shoots of the persimmon trees collected at 26 April 2011 mainly due to foliar uptake. The concentrations were 1.1 kBq/kg-dry for {sup 137}Cs and 1.3 kBq/kg-dry for {sup 134}Cs. After that, continuous sampling of leaves, branches and fruits of the persimmon trees had been carried out for two years. Immediately after the collection, samples were transferred to our laboratory and weighed to obtain fresh weight. Leaf samples were usually separated into two portions; one portion was washed with tap water to remove dust from the surface and the other portion was not treated. For fruit samples, if it is possible, fruit flesh, peal and non-edible part were separated. All the samples were oven-dried at 80 deg. C for three days at least. Each dried sample was chopped into fine pieces, mixed well, and then transferred into plastic vessels separately. Radioactivity concentration was measured by a Ge-detecting system (Seiko EG and G Ortec) using 3000-40000 s counting intervals. By August 14, 2013, about 140 samples were collected from the trees; about 60 samples were leaves (both washed and untreated). Radiocesium concentrations in tree leaves decreased with time, and the effective half-life was about 190 d; the value was similar to those in branches (160 d for new branches, and 250 d for 1-2 y.o. branches) and fruits (250 d for fruit flesh and 230 d for peals). Thus we concluded that the half-life of radiocesium in

  9. Energy dependence of average half-life of delayed neutron precursors in fast neutron induced fission of 235U and 236U

    International Nuclear Information System (INIS)

    Isaev, S.G.; Piksaikin, L.E.; Kazakov, L.E.; Tarasko, M.Z.

    2000-01-01

    The measurements of relative abundances and periods of delayed neutrons from fast neutron induced fission of 235 U and 236 U have been made at the electrostatic accelerator CG-2.5 at IPPE. The preliminary results were obtained and discussed in the frame of the systematics of the average half-life of delayed neutron precursors. It was shown that the average half-life value in both reactions depends on the energy of primary neutrons [ru

  10. Tests of the methods of analysis of picosecond lifetimes and measurement of the half-life of the 569.6 keV level in 207Pb

    International Nuclear Information System (INIS)

    Lima, E. de; Kawakami, H.; Lima, A. de; Hichwa, R.; Ramayya, A.V.; Hamilton, J.H.; Dunn, W.; Kim, H.J.

    1978-01-01

    Customarily one extracts the half-life of the nuclear state from a delayed time spectrum by an analysis of the centroid shift, the slope and lately by the convolution method. Recently there have been two formulas relating the centroid shift to the half-life of the nuclear state. These two procedures can give different results for the half-life when Tsub(1/2) the same order or less than the time width of one channel. An extensive investigation of these two formulas and precedures has been made by measuring the half-life of the first excited state in 207 Pb at 569.6 keV. This analysis confirms Bay's formula relating the centroid shift to the half-life of the state. The half-life of the 569.6 keV level in 207 Pb is measured to be (129+-3) ps in excellent agreement with Weisskopf's single particle estimate of 128 ps for an E2 transition. (Auth.)

  11. KINETIC MODELLING AND HALF LIFE STUDY OF ADSORPTIVE BIOREMEDIATION OF SOIL ARTIFICIALLY CONTAMINATED WITH BONNY LIGHT CRUDE OIL

    Directory of Open Access Journals (Sweden)

    Samuel Enahoro Agarry

    2015-06-01

    Full Text Available In this study, comparative potential effects of commercial activated carbon (CAC and plantain peel-derived biochar (PPBC of different particle sizes and dosage to stimulate petroleum hydrocarbon biodegradation in soil were investigated. Microcosms containing soil were spiked with weathered Bonny light crude oil (WBLCO (10% w/w and amended with different particle sizes (0.02, 0.07 and 0.48 mm and dosage (20, 30 and 40 g of CAC and PPBC, respectively. The bioremediation experiments were carried out for a period of 28 days under laboratory conditions. The results showed that there was a positive relationship between the rate of petroleum hydrocarbons reduction and presence of the CAC and PPBC in crude oil contaminated soil microcosms. The WBLCO biodegradation data fitted well to the first-order kinetic model. The model revealed that WBLCO contaminated-soil microcosms amended with CAC and PPBC had higher biodegradation rate constants (k as well as lower half-life times (t1/2 than unamended soil (natural attenuation remediation system. The rate constants increased while half-life times decreased with decreased particle size and increased dosage of amendment agents. ANOVA statistical analysis revealed that WBLCO biodegradation in soil was significantly (p = 0.05 influenced by the addition of CAC and biochar amendment agents, respectively. However, Tukey’s post hoc test (at p = 0.05 showed that there was no significant difference in the bioremediation efficiency of CAC and PPBC. Thus, amendment of soils with biochar has the potential to be an inexpensive, efficient, environmentally friendly and relatively novel strategy to mitigate organic compound-contaminated soil.

  12. Number of infection events per cell during HIV-1 cell-free infection.

    Science.gov (United States)

    Ito, Yusuke; Remion, Azaria; Tauzin, Alexandra; Ejima, Keisuke; Nakaoka, Shinji; Iwasa, Yoh; Iwami, Shingo; Mammano, Fabrizio

    2017-07-26

    HIV-1 accumulates changes in its genome through both recombination and mutation during the course of infection. For recombination to occur, a single cell must be infected by two HIV strains. These coinfection events were experimentally demonstrated to occur more frequently than would be expected for independent infection events and do not follow a random distribution. Previous mathematical modeling approaches demonstrated that differences in target cell susceptibility can explain the non-randomness, both in the context of direct cell-to-cell transmission, and in the context of free virus transmission (Q. Dang et al., Proc. Natl. Acad. Sci. USA 101:632-7, 2004: K. M. Law et al., Cell reports 15:2711-83, 2016). Here, we build on these notions and provide a more detailed and extensive quantitative framework. We developed a novel mathematical model explicitly considering the heterogeneity of target cells and analysed datasets of cell-free HIV-1 single and double infection experiments in cell culture. Particularly, in contrast to the previous studies, we took into account the different susceptibility of the target cells as a continuous distribution. Interestingly, we showed that the number of infection events per cell during cell-free HIV-1 infection follows a negative-binomial distribution, and our model reproduces these datasets.

  13. Merkel cell polyomavirus infection and Merkel cell carcinoma.

    Science.gov (United States)

    Liu, Wei; MacDonald, Margo; You, Jianxin

    2016-10-01

    Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Alteration of cell cycle progression by Sindbis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  15. Alteration of cell cycle progression by Sindbis virus infection

    International Nuclear Information System (INIS)

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-01-01

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G 1 phase preferred to proliferate during S/G 2 phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G 1 phase than in cells infected during S/G 2 phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases

  16. Cells in Dengue Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  17. Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening.

    Science.gov (United States)

    Read, Thomas; Olkhov, Rouslan V; Williamson, E Diane; Shaw, Andrew M

    2015-09-01

    A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

  18. HPLC Analysis to Determine the Half-life and Bioavailability of the Termiticides Bifenthrin and Fipronil in Soil.

    Science.gov (United States)

    Manzoor, F; Pervez, M

    2017-12-05

    The aim of this study was to test the bioavailability and degradation in soil of the termiticides bifenthrin and fipronil, which are used to treat subterranean termites (Heterotermes indicola, Wasmann). Soil collected from different areas of Lahore was categorized as sandy clay loam (SCL) or sandy loam (SL). Laboratory bioassays were conducted to determine the bioavailability ratio of bifenthrin and fipronil in each type of soil after different periods of time. LT50 values were determined posttreatment at different time intervals. Regarding soil type, both termiticides were more effective in SL soil, compared with SCL soil posttreatment. There were significant differences in termite mortality in treated compared with untreated control samples (P bifenthrin (maximum, 1,002 and 1,262 d in SCL soil and SL soil, respectively) indicated that it persisted in both soil types at all concentrations. The maximum calculated half-life values of fipronil were 270 and 555 d in SCL and SL soil, respectively. At lower concentrations and over longer periods of time, fipronil completely degraded in SL soil, while a negligible amount was detected in SCL soil. Termiticide concentration decreased over time, as did the termiticide recovery rate. Overall, bifenthrin was more persistent than fipronil under all treatment conditions tested. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Degradation and half-life of DNA present in biomass from a genetically-modified organism during land application.

    Science.gov (United States)

    Halter, Mathew C; Zahn, James A

    2017-02-01

    White biotechnology has made a positive impact on the chemical industry by providing safer, more efficient chemical manufacturing processes that have reduced the use of toxic chemicals, harsh reaction conditions, and expensive metal catalysts, which has improved alignment with the principles of Green Chemistry. The genetically-modified (GM) biocatalysts that are utilized in these processes are typically separated from high-value products and then recycled, or eliminated. Elimination routes include disposal in sanitary landfills, incineration, use as a fuel, animal feed, or reuse as an agricultural soil amendment or other value-added products. Elimination routes that have the potential to impact the food chain or environment have been more heavily scrutinized for the fate and persistence of biological products. In this study, we developed and optimized a method for monitoring the degradation of strain-specific DNA markers from a genetically-modified organism (GMO) used for the commercial production of 1,3-propanediol. Laboratory and field tests showed that a marker for heterologous DNA in the GM organism was no longer detectable by end-point polymerase chain reaction (PCR) after 14 days. The half-life of heterologous DNA was increased by 17% (from 42.4 to 49.7 h) after sterilization of the soil from a field plot, which indicated that abiotic factors were important in degradation of DNA under field conditions. There was no evidence for horizontal transfer of DNA target sequences from the GMO to viable organisms present in the soil.

  20. Dependence of Rn adsorption rate and effective half-life time on diffusion barrier type and moving air environment

    International Nuclear Information System (INIS)

    Arafa, Wafaa; Badran, Heba

    2005-01-01

    The variation of the adsorbed radon rate during the exposure time using charcoal canister was studied applying moving air environment inside the radon chamber and compared to the static air measurements. The air movement increases the accumulation time leading to more accurate results. Different types of membrane have been tested as diffusion barrier for activated charcoal canisters. The Makrofol and aluminized polycarbonate improve the adsorption/desorption rate more than the polyehylene membrane. The measured effective half-life time showed a remarkable correlation with the previously measured permeability constant for corresponding membranes. Different types of commercially available charcoal were investigated to develop a local version of charcoal canister for radon measurements. Applying static and moving air environments, the break point and radon collection efficiency were determined at different temperatures. Both of the temperature and air movement accelerate the appearance of the break point. Th efficiency of the locally developed charcoal is 87% and 84.5% of that Calgon PCB charcoal used by EPA. (author)

  1. Development of controller of acquisition and sample positioner for activation for use in measurements of short half-life radioisotopes

    International Nuclear Information System (INIS)

    Secco, Marcello

    2016-01-01

    High resolution gamma spectroscopy measurements have several applications. Those involving short half-life radioisotope measurements may present low precision problems when the radioactive source is far from detector end cup and in the very high activity situations also can present accuracy loss due to dead time and pile-up effects. A way to overcome these problems is changing the source detector distance as the activity is decreasing, and thereby maximizing the statistical counting. In the present study, the Controller of Acquisition and Sample Positioner for Activation (CASPA) was developed. It is a low cost and weight device, made with low atomic number materials designed to assist gamma spectroscopy measurements, which is able to control the distance between the source and the detector, even allowing that there is a change of this distance during the measurement process. Because it is automated it optimizes the time of the operator, who has complete freedom to program their routine measurements in the device besides minimizing the radiation dose in the operator. An interface that allow the user control the CASPA system and to program the acquisition system was created. Tests aiming to optimize the operation of CASPA system were carried out and the safety of the CASPA operation was verified, it was not presented any failure during their tests. It was applied the repeatability tests by the acquisition 60 Co standard source and was found that the positioning of automated system has reproduced the results of static system with a 95% of confidence level. (author)

  2. Increased half-life and enhanced potency of Fc-modified human PCSK9 monoclonal antibodies in primates.

    Directory of Open Access Journals (Sweden)

    Yijun Shen

    Full Text Available Blocking proprotein convertase subtilisin kexin type 9 (PCSK9 binding to low-density lipoprotein receptor (LDLR can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs, alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules. We engineered several variants with two or three amino acid substitutions in the Fc fragment based on prior knowledge. The Fc-modified mAbs exhibited increased binding to FcRn, resulting in prolonged serum half-life and enhanced efficacy in vivo. These results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood.

  3. Diffusion and release of noble gas and halogen fission products with several days half-life in UO2 particle

    International Nuclear Information System (INIS)

    Fang Chao

    2013-01-01

    The exact solutions of diffusion and release model of noble gas and halogen fission products in UO 2 particle of HTGR were built under the conditions of adsorption effect and other physical processes. The corresponding release fractions (F(t)) and the ratio of release and productive amounts (R(t)/B (t)) of fission products were also derived. Furthermore, the F(t) and R(t)/B(t) of 131 I, 131 IXe m , 133 Xe and 133 Xe m whose half-lifes are several days in UO 2 particle with the exact solutions, approximate solutions and corresponding numerical solutions under different temperature histories of reactor core were investigated. The results show that the F(t) and R(t)/B(t) are different in numerical values unless the time of release is long enough. The properties of conservation of exact solutions are much more reasonable than the ones of approximate solutions. It is also found that the results of exact solutions approach the actual working conditions more than the approximate and numerical solutions. (author)

  4. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

    Directory of Open Access Journals (Sweden)

    Cai Y

    2014-07-01

    Full Text Available Yunpeng Cai,1,2 Mingxin Xu,2 Minglu Yuan,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Since the availability of recombinant human growth hormone (rhGH enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot® microsphere and injectors (Zomajet®, Serojet®, and NordiFlex®. Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. Keywords: intranasal, pulmonary, transdermal, microsphere, microneedle, hydrogel

  5. Zika virus infection of Hofbauer cells.

    Science.gov (United States)

    Simoni, Michael K; Jurado, Kellie Ann; Abrahams, Vikki M; Fikrig, Erol; Guller, Seth

    2017-02-01

    Recent studies have linked antenatal infection with Zika virus (ZIKV) with major adverse fetal and neonatal outcomes, including microcephaly. There is a growing consensus for the existence of a congenital Zika syndrome (CZS). Previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (DENV), a closely related flavivirus. As the placenta provides the conduit for vertical transmission of certain viruses, and placental Hofbauer cells (HBCs) are fetal-placental macrophages located adjacent to fetal capillaries, it is not surprising that several recent studies have examined infection of HBCs by ZIKV. In this review, we describe congenital abnormalities associated with ZIKV infection, the role of HBCs in the placental response to infection, and evidence for the susceptibility of HBCs to ZIKV infection. We conclude that HBCs may contribute to the spread of ZIKV in placenta and promote vertical transmission of ZIKV, ultimately compromising fetal and neonatal development and function. Current evidence strongly suggests that further studies are warranted to dissect the specific molecular mechanism through which ZIKV infects HBCs and its potential impact on the development of CZS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Half-life, branching-ratio, and Q-value measurement for the superallowed 0+→0+β+ emitter 42Ti

    International Nuclear Information System (INIS)

    Nieto, T. Kurtukian; Souin, J.; Audirac, L.; Blank, B.; Giovinazzo, J.; Eronen, T.; Aeystoe, J.; Elomaa, V.-V.; Hager, U.; Hakala, J.; Jokinen, A.; Kankainen, A.; Karvonen, P.; Kessler, T.; Moore, I. D.; Penttilae, H.; Rahaman, S.; Reponen, M.; Rissanen, J.; Saastamoinen, A.

    2009-01-01

    The half-life, the branching ratio, and the decay Q value of the superallowed β emitter 42 Ti were measured in an experiment performed at the JYFLTRAP facility of the Accelerator Laboratory of the University of Jyvaeskylae. 42 Ti is the heaviest T z =-1 nucleus for which high-precision measurements of these quantities have been tried. The half-life (T 1/2 =208.14±0.45 ms) and the Q value [Q EC =7016.83(25) keV] are close to or reach the required precision of about 0.1%. The branching ratio for the superallowed decay branch [BR=47.7(12)%], a by-product of the half-life measurement, does not reach the necessary precision yet. Nonetheless, these results allow one to determine the experimental ft value and the corrected Ft value to be 3114(79) and 3122(79) s, respectively.

  7. Analysis of existing data and specification of an experiment to determine the 252Cf half-life to the required degree of accuracy

    International Nuclear Information System (INIS)

    Lorenz, A.; Kharitonov, I.A.

    1994-02-01

    The methods used and the results obtained in measurements of the 252 Cf half-life are analyzed. In calculating the weighted mean value, additional error components as well as those given by the authors are taken into account. In order to reduce the error in the weighted mean value to less than 0.1%, the need and the requirements for an exact measurement are specified. A half-life of 2.6473±0.0028 years is recommended. (author). 16 refs, 3 tabs

  8. High-precision half-life measurements of the T=1/2 mirror beta decays F-17 and Cl-33

    OpenAIRE

    Grinyer, J; Grinyer, G. F; Babo, Mathieu; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J. C; Traykov, E

    2015-01-01

    Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, 17F and 33Cl, in order to eliminate the half-life as th...

  9. High-precision half-life measurements of the T=1/2 mirror β decays F17 and Cl33

    OpenAIRE

    Grinyer, J; Grinyer, G F; Babo, M; Bouzomita, H; Chauveau, P; Delahaye, P; Dubois, M; Frigot, R; Jardin, P; Leboucher, C; Maunoury, L; Seiffert, C; Thomas, J C; Traykov, E

    2015-01-01

    Background: Measurements of the ft values for T=1/2 mirror β+ decays offer a method to test the conserved vector current hypothesis and to determine Vud, the up-down matrix element of the Cabibbo-Kobayashi-Maskawa matrix. In most mirror decays used for these tests, uncertainties in the ft values are dominated by the uncertainties in the half-lives. Purpose: Two precision half-life measurements were performed for the T=1/2β+ emitters, F17 and Cl33, in order to eliminate the half-life as the le...

  10. A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life

    DEFF Research Database (Denmark)

    Jensen, Pernille Foged; Schoch, Angela; Larraillet, Vincent

    2017-01-01

    The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism...... half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct...

  11. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  12. Studies on the mechanism of the epileptiform activity induced by U18666A. II. concentration, half-life and distribution of radiolabeled U18666A in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Cenedella, R.J.; Sarkar, C.P.; Towns, L.

    1982-06-01

    The concentration, half-life, and distribution in brain of U18666A, a drug that can drastically alter cerebral lipids and induce a chronic epileptiform state, was determined following both acute and chronic drug administration. U18666A specifically labeled with tritium was prepared by custom synthesis. Brain levels of 1 x 10(-6)M and higher were reached soon after giving an acute 10-mg/kg dose (i.p. or s.c.) of U18666A containing 7-/sup 3/H-U18666A of known specific activity. A steady state concentration of 1 to 2 x 10(-6)M was reached with chronic injection of 10 mg/kg every 4th day, a treatment schedule that results in altered brain lipids and induction of epilepsy if begun soon after birth. The disappearance of U18666A from both brain and serum was described by two similar biexponential processes, a brief rapid clearance (t1/2 . 10 h) and a sustained and much slower one (t1/2 . 65 h). Brain levels of the drug were about 10 times higher than serum at all times examined. Few differences were seen in the regional distribution of radiolabeled drug in brain as determined by both direct analysis and by autoradiographic examination; but the drug did concentrate in lipid-rich subcellular fractions. For example, the synaptosome and myelin fractions each contained about 25-35% of both the total /sup 3/H-labeled drug and total lipid in whole brain. The lipid composition of these fractions was drastically altered in treated animals. In conclusion, the chronic epileptiform state induced by U18666A does not appear to involve localization of the drug in a specific brain region or particular cell type. Rather, the condition could involve localization of the drug in lipid-rich membranes and marked changes in the composition of these membranes.

  13. Measurement of the half-life of 60Fe using the Argonne FN tandem-superconducting Linac system as an accelerator mass spectrometer

    International Nuclear Information System (INIS)

    Kutschera, W.; Billquist, P.J.; Frekers, D.

    1983-01-01

    An experiment to improve the accuracy in the half-life value of 60 Fe by measuring both the amount of 60 Fe nuclei and the decay-rate of a spallation produced sample using the relation dN/dt = -lambda N is briefly discussed

  14. Glucagon-like Peptide 1 Conjugated to Recombinant Human Serum Albumin Variants with Modified Neonatal Fc Receptor Binding Properties. Impact on Molecular Structure and Half-Life

    DEFF Research Database (Denmark)

    Bukrinski, Jens T.; Sønderby, Pernille; Antunes, Filipa

    2017-01-01

    Glucagon-like peptide 1 (GLP-1) is a small incretin hormone stimulated by food intake, resulting in an amplification of the insulin response. Though interesting as a drug candidate for the treatment of type 2 diabetes mellitus, its short plasma half-life of less than 3 minutes limits its clinical...... use. A strategy to extend the half-life of GLP-1 utilizes the long half-life of human serum albumin (HSA) by combining the two via chemical conjugation or genetic fusion. HSA has a plasma half-life of around 21 days owing to its interaction with the neonatal Fc receptor (FcRn) expressed in endothelial...... with the available structural information on the FcRn and GLP-1 receptor (GLP-1R) obtained from X-ray crystallography, we can explain the observed in-vitro and in-vivo behaviour. We conclude that the conjugation of GLP-1 to rHSA does not affect the interaction between rHSA and FcRn, while the observed decrease...

  15. New limit on the half-life of 78Kr with respect to the 2K(2ν)-capture decay mode

    International Nuclear Information System (INIS)

    Gavriljuk, Ju.M.; Kuzminov, V.V.; Osetrova, N.Ya.; Ratkevich, S.S.

    2000-01-01

    The features of data accumulated for 1817 h in an experimental search for the 2K(2ν)-capture mode of 78 Kr decay are discussed. A new limit on the half-life for this decay is found: T 1sol2 ≥ 2.3 x 10 20 yr (at a 90% C.L.)

  16. Platelet half-life in patients with primary hyperlipoproteinemia type IIa, IIb, and IV according to Fredrickson with and without clinical signs of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, E; Sinzinger, H; Widhalm, K; Kaliman, J; Hoefer, R [Vienna Univ. (Austria). 2. Medizinische Klinik; Ludwig Boltzmann-Institut fuer Nuklearmedizin, Vienna (Austria); Vienna Univ. (Austria). Kinderklinik; Vienna Univ. (Austria). Kardiologische Klinik)

    1982-09-01

    It is generally accepted that platelet half-life is shortened in atherosclerotic vascular diseases. Concerning changes due to hyperlipoproteinemia (HLP), however, there exist only few data. Therefore, we examined the platelet-half life in 60 patients with recently discovered HLP type IIa, IIb and IV according to Fredrickson before treatment in comparison to 60 controls. 33 of the HLP-patients had no clinical symptoms of angiopathy. 27 patients suffered from peripheral vascular disease or from coronary heart disease as verified by angiography. The labelling of autologous platelets was performed with 100..mu..Ci of /sup 111/Indium-oxine-sulfate at 37/sup 0/C for 5 minutes. The mean labelling efficiency was 90%, the recovery after 2 hours about 70%. Serum lipoproteins were estimated by means of ultracentrifugation and polyanionprecipitation according to Lipid Research Clinic Methods. In the patients with HLP platelet half-life was significantly shortened in comparison to the control group (p < 0.01). These changes were most pronounced in patients with HLP-type IIa and with atherosclerotic lesions, respectively. In patients with HLP-type IIa a very close correlation could be demonstrated between platelet half-life and LDL-cholesterol (r = -0.72; p < 0.001) as well as total cholesterol (r = -0.73; p < 0.001). These data prove that in HLP in-vivo platelet function as measured by platelet survival is significantly influenced even before the occurrence of clinically relevant symptoms of atherosclerosis.

  17. Fast renal trapping of porcine Luteinizing Hormone (pLH shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life

    Directory of Open Access Journals (Sweden)

    Locatelli Alain

    2003-10-01

    Full Text Available Abstract Background Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH and equine CG (eCG which exhibit respectively a short and a long half-life. This was done first by following half-lives of pLH in piglets with hepatic portal circulation shunted or not. It was expected that such a shunt would enhance the short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and 123I-eCG was performed in intact rats to compare their routes and rates of distribution and elimination. Methods Native pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anæsthetized piglet. Blood samples were recovered sequentially over one hour time and the hormone concentrations were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and 123I-eCG was performed in rats using a OPTI-CGR gamma camera. Results In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min. In the rat, the half-life of pLH was also found to be very short (3–6 min and 123I-pLH was found to accumulate in high quantity in less than 10 min post injection at the level of kidneys but not in the liver. 123I-eCG didn't accumulate in any organ in the rats during the first hour, plasma concentrations of this gonadotropin being still elevated (80% at this time. Conclusion In both the porcine and rat species, the liver is not responsible for the rapid elimination of pLH from the circulation compared to eCG. Our scintigraphic experiments suggest that the very short circulatory half-life of LH is due to rapid renal trapping.

  18. A new value for the half-life of {sup 10}Be by Heavy-Ion Elastic Recoil Detection and liquid scintillation counting

    Energy Technology Data Exchange (ETDEWEB)

    Korschinek, G., E-mail: Gunther.Korschinek@ph.tum.d [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Bergmaier, A. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Faestermann, T. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Gerstmann, U.C. [Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Radiation Protection, Ingolstaedter Landstr. 1, D-85764 Neuherberg (Germany); Knie, K.; Rugel, G. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Wallner, A. [VERA Laboratory, Faculty of Physics, University of Vienna, Waehringer Strasse 17, A-1090 Wien (Austria); Dillmann, I. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Dollinger, G. [Universitaet der Bundeswehr Muenchen, Fakultaet fuer Luft- und Raumfahrttechnik, Institut fuer Angewandte Physik und Messtechnik LRT2, Werner-Heisenberg-Weg 39, D-85577 Neubiberg (Germany); Lierse von Gostomski, Ch. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany); Kossert, K. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Maiti, M.; Poutivtsev, M. [Physik Department, Technische Universitaet Muenchen, D-85748 Garching (Germany); Remmert, A. [Lehrstuhl fuer Radiochemie, Technische Universitaet Muenchen, D-85748 Garching (Germany)

    2010-01-15

    The importance of {sup 10}Be in different applications of accelerator mass spectrometry (AMS) is well-known. In this context the half-life of {sup 10}Be has a crucial impact, and an accurate and precise determination of the half-life is a prerequisite for many of the applications of {sup 10}Be in cosmic-ray and earth science research. Recently, the value of the {sup 10}Be half-life has been the centre of much debate. In order to overcome uncertainties inherent in previous determinations, we introduced a new method of high accuracy and precision. An aliquot of our highly enriched {sup 10}Be master solution was serially diluted with increasing well-known masses of {sup 9}Be. We then determined the initial {sup 10}Be concentration by least square fit to the series of measurements of the resultant {sup 10}Be/{sup 9}Be ratio. In order to minimize uncertainties because of mass bias which plague other low-energy mass spectrometric methods, we used for the first time Heavy-Ion Elastic Recoil Detection (HI-ERD) for the determination of the {sup 10}Be/{sup 9}Be isotopic ratios, a technique which does not suffer from difficult to control mass fractionation. The specific activity of the master solution was measured by means of accurate liquid scintillation counting (LSC). The resultant combination of the {sup 10}Be concentration and activity yields a {sup 10}Be half-life of T{sub 1/2} = 1.388 +- 0.018 (1 s, 1.30%) Ma. In a parallel but independent study (Chmeleff et al. ), found a value of 1.386 +- 0.016 (1.15%) Ma. Our recommended weighted mean and mean standard error for the new value for {sup 10}Be half-life based on these two independent measurements is 1.387 +- 0.012 (0.87%) Ma.

  19. Analytical studies by activation. Part A and B: Counting of short half-life radio-nuclides. Part C: Analytical programs for decay curves

    International Nuclear Information System (INIS)

    Junod, E.

    1966-03-01

    Part A and B: Since a radio-nuclide of short half-life is characterized essentially by the decrease in its activity even while it is being measured, the report begins by recalling the basic relationships linking the half-life the counting time, the counting rate and the number of particles recorded. The second part is devoted to the problem of corrections for counting losses due to the idle period of multichannel analyzers. Exact correction formulae have been drawn up for the case where the short half-life radionuclide is pure or contains only a long half-life radio-nuclide. By comparison, charts have been drawn up showing the approximations given by the so-called 'active time' counting and by the counting involving the real time associated with a measurement of the overall idle period, this latter method proving to be more valid than the former. A method is given for reducing the case of a complex mixture to that of a two-component mixture. Part C: The problems connected with the qualitative and quantitative analysis of the decay curves of a mixture of radioactive sources of which one at least has a short half-life are presented. A mathematical description is given of six basic processes for which some elements of Fortran programs are proposed. Two supplementary programs are drawn up for giving an overall treatment of problems of dosage in activation analysis: one on the basis of a simultaneous irradiation of the sample and of one or several known samples, the other with separate irradiation of the unknown and known samples, a dosimeter (activation, or external) being used for normalizing the irradiation flux conditions. (author) [fr

  20. Lithium as an adjunct to radioiodine therapy in Graves' disease for prolonging the intrathyroidal effective half-life of radioiodine. Useful or not?

    Energy Technology Data Exchange (ETDEWEB)

    Dunkelmann, S.; Kuenstner, H.; Nabavi, E.; Eberlein, U.; Groth, P.; Schuemichen, C. [Rostock Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin, Zentrum fuer Radiologie

    2006-07-01

    Aim: Evaluation of intrathyroidal kinetics of radioiodine with and without lithium as adjunct with respect to the increase in radiation dose delivered to the thyroid. Patients, methods: 267 patients in three groups were included in the study. Group I with 227 patients served as control group, Group II with 21 patients and Group III with 19 patients were distinguished by an intrathyroidal half-life of radioiodine below 3.5 days in the diagnostic test. Patients in Group III received 885 mg lithium carbonate a day for 2 weeks as adjunct to radioiodine therapy. Both diagnostic and therapeutic radioiodine kinetics were followed up by at least 10 uptake measurements within a minimum of 48 h. Kinetics of radioiodine were defined mathematically as balance of the thyroidal iodine intake and excretion by a two-compartment model. Results: Under therapy the maximum uptake of radioiodine was reduced by nearly 10% in all groups, in Group I, the effective half-life as well as the product of maximum uptake x effective half-life as an equivalent of radiation dose independent of thyroid volume was lowered in the same magnitude. In Group II, the energy-dose equivalent remained constant under therapy. With adjunct lithium in Group III, the effective half-life was prolonged significantly by factor 1.61{+-}0.49 and the volume-independent energy-dose equivalent by factor 1.39{+-}0.37. No severe side effects of lithium were observed. Conclusion: Using lithium as adjunct to radio-iodine therapy increases the radiation dose delivered to the thyroid by 39% on average and nearly 30% of radioiodine activity can be saved in these patients. Lithium is recommended in patients with very short effective half-life in the diagnostic test in order to reduce the activity required and whole-body radiation dose. (orig.)

  1. Effective Half-life of I-131 in Patients with Differentiated Thyroid Cancer Treated by Radioactive I-131

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seok Gun [Dankook University, Cheonan (Korea, Republic of)

    2008-12-15

    Effective half life of I-131 (T{sub eff}) in patients with differentiated thyroid cancer treated by I-131 is must-know value for dose calculation and determination of release time from isolation room. There has been no report about T{sub eff} in Koreans. Thus, author tried to measure dose rate without radiation exposure to faculty members and calculated T{sub eff}. Probe of radiation survey meter was fixed at the wall of isolation room, and body of survey meter was placed outside the room. With this simple arrangement, author could measure radiation frequently without radiation exposure to faculty members in 68 patient (F=55, M=13, age=47{+-}13.7) treated by I-131 (3.7{approx}7.4 GBq) for differentiated thyroid cancer from Jan 2006 to Dec 2006. From this data, T{sub eff}, 48 hr retention rate, and the time necessary to whole body retention of I-131 become less than 1.1 GBq were calculated. Serum creatinine levels were measured before and after thyroid hormone withdrawal. T{sub eff} was 15.4{+-}4.3 hr (9.4{approx}32.5 hr). There was a loose correlation between T{sub eff} and serum creatinine concentration (r=0.45). 48hr retention was 4.9{+-}4.2% (1{approx}23%). Time necessary to whole body retention of I-131 become less than 1.1 GBq was calculated as 47.1{+-}13.2 hr for 9.25 GBq, 42.1{+-}11.9 hr for 7.4 GBq, 35.7{+-}10.0 hr for 5.55 GBq, and 26.7{+-}7.5 hr for 3.7 GBq dose of I-131. Author successfully measured radiation dose rates in isolated patients treated by high dose of I-131 without radiation exposure to the faculty members with simple arrangement of survey meter probe. Using those data, T{sub eff} and some other indices were calculated.

  2. Determining thyroid {sup 131}I effective half-life for the treatment planning of Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Willegaignon, Jose; Sapienza, Marcelo T.; Barberio Coura Filho, George; Buchpiguel, Carlos A. [Cancer Institute of Sao Paulo State (ICESP), Clinical Hospital, School of Medicine, University of Sao Paulo, Sao Paulo 01246-000 (Brazil); Nuclear Medicine Service, Department of Radiology, School of Medicine, University of Sao Paulo, Sao Paulo 01246-000 (Brazil); Traino, Antonio C. [Unit of Medical Physics, Azienda Ospedaliero-Universitaria Pisana, Pisa 56126 (Italy)

    2013-02-15

    Purpose: Thyroid {sup 131}I effective half-life (T{sub eff}) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple {sup 131}I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T{sub eff}, these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T{sub eff} for dosimetric purposes. Methods: A total of 50 patients with GD were included in this prospective study. Thyroidal {sup 131}I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T{sub eff} was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). Results: When considering all the measured points, the representative T{sub eff} for all the patients was 6.95 ({+-}0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 ({+-}0.81), 6.90 ({+-}0.81), and 6.95 ({+-}0.81) days, respectively. According to the mean deviations 2.2 ({+-}2.4)%, 2.1 ({+-}2.0)%, and 0.04 ({+-}0.09)% found in T{sub eff}, calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). Conclusions: T{sub eff} obtained from only two thyroid {sup 131}I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning of

  3. Oral epithelial cells are susceptible to cell-free and cell-associated HIV-1 infection in vitro

    International Nuclear Information System (INIS)

    Moore, Jennifer S.; Rahemtulla, Firoz; Kent, Leigh W.; Hall, Stacy D.; Ikizler, Mine R.; Wright, Peter F.; Nguyen, Huan H.; Jackson, Susan

    2003-01-01

    Epithelial cells lining the oral cavity are exposed to HIV-1 through breast-feeding and oral-genital contact. Genital secretions and breast milk of HIV-1-infected subjects contain both cell-free and cell-associated virus. To determine if oral epithelial cells can be infected with HIV-1 we exposed gingival keratinocytes and adenoid epithelial cells to cell-free virus and HIV-1-infected peripheral blood mononuclear cells and monocytes. Using primary isolates we determined that gingival keratinocytes are susceptible to HIV-1 infection via cell-free CD4-independent infection only. R5 but not X4 viral strains were capable of infecting the keratinocytes. Further, infected cells were able to release infectious virus. In addition, primary epithelial cells isolated from adenoids were also susceptible to infection; both cell-free and cell-associated virus infected these cells. These data have potential implications in the transmission of HIV-1 in the oral cavity

  4. Defective Natural Killer cell antiviral capacity in paediatric HBV infection

    DEFF Research Database (Denmark)

    Heiberg, Ida Louise; Laura J., Pallett; Winther, Thilde Nordmann

    2015-01-01

    Natural Killer (NK) cells exhibit dysregulated effector function in adult chronic HBV infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK...... cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell IFN-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells...

  5. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  6. Measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Alduino, C.; Avignone, F.T.; Chott, N.; Creswick, R.J.; Rosenfeld, C.; Wilson, J. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); Alfonso, K.; Hickerson, K.P.; Huang, H.Z.; Liu, X.; Trentalange, S.; Zhu, B.X. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Artusa, D.R. [University of South Carolina, Department of Physics and Astronomy, Columbia, SC (United States); INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Azzolini, O.; Camacho, A.; Keppel, G.; Palmieri, V.; Pira, C. [INFN-Laboratori Nazionali di Legnaro, Legnaro, Padova (Italy); Banks, T.I.; Drobizhev, A.; Freedman, S.J.; Hennings-Yeomans, R.; O' Donnell, T.; Wagaarachchi, S.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Bari, G.; Deninno, M.M. [INFN-Sezione di Bologna, Bologna (Italy); Beeman, J.W. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); Bellini, F.; Cardani, L.; Casali, N.; Cosmelli, C.; Ferroni, F. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Bersani, A.; Caminata, A. [INFN-Sezione di Genova, Genova (Italy); Biassoni, M.; Carbone, L.; Cremonesi, O.; Ferri, E.; Giachero, A.; Pessina, G.; Previtali, E.; Rusconi, C. [INFN-Sezione di Milano Bicocca, Milan (Italy); Brofferio, C.; Capelli, S.; Carniti, P.; Cassina, L.; Chiesa, D.; Clemenza, M.; Faverzani, M.; Fiorini, E.; Gironi, L.; Gotti, C.; Maino, M.; Nucciotti, A.; Pavan, M.; Pozzi, S.; Sisti, M.; Terranova, F.; Zanotti, L. [Universita di Milano-Bicocca, Dipartimento di Fisica, Milan (Italy); INFN-Sezione di Milano Bicocca, Milan (Italy); Bucci, C.; Cappelli, L.; D' Addabbo, A.; Di Vacri, M.L.; Gorla, P.; Pattavina, L.; Pirro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Canonica, L. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Massachusetts Institute of Technology, Cambridge, MA (United States); Cao, X.G.; Fang, D.Q.; Ma, Y.G.; Wang, H.W.; Zhang, G.Q. [Chinese Academy of Sciences, Shanghai Institute of Applied Physics, Shanghai (China); Copello, S.; Di Domizio, S.; Fernandes, G.; Marini, L.; Pallavicini, M. [INFN-Sezione di Genova, Genova (Italy); Universita di Genova, Dipartimento di Fisica, Genova (Italy); Cushman, J.S.; Davis, C.J.; Heeger, K.M.; Lim, K.E.; Maruyama, R.H. [Yale University, Department of Physics, New Haven, CT (United States); Dafinei, I.; Morganti, S.; Mosteiro, P.J.; Orio, F.; Pettinacci, V.; Tomei, C.; Vignati, M. [INFN-Sezione di Roma, Rome (Italy); Dell' Oro, S. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); INFN-Gran Sasso Science Institute, L' Aquila (Italy); Feintzeig, J.; Fujikawa, B.K.; Mei, Y.; Smith, A.R. [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Franceschi, M.A.; Ligi, C.; Napolitano, T.; Piperno, G. [INFN-Laboratori Nazionali di Frascati, Frascati, Rome (Italy); Giuliani, A.; Tenconi, M. [Universite Paris-Saclay, CSNSM, Univ. Paris-Sud, CNRS/IN2P3, Orsay (France); Gladstone, L.; Leder, A.; Winslow, L.A. [Massachusetts Institute of Technology, Cambridge, MA (United States); Gutierrez, T.D. [California Polytechnic State University, Physics Department, San Luis Obispo, CA (United States); Haller, E.E. [Lawrence Berkeley National Laboratory, Materials Science Division, Berkeley, CA (United States); University of California, Department of Materials Science and Engineering, Berkeley, CA (United States); Han, K. [Yale University, Department of Physics, New Haven, CT (United States); Shanghai Jiao Tong University, Department of Physics and Astronomy, Shanghai (China); Hansen, E. [University of California, Department of Physics and Astronomy, Los Angeles, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Kadel, R. [Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Kolomensky, Yu.G. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Physics Division, Berkeley, CA (United States); Martinez, M. [Sapienza Universita di Roma, Dipartimento di Fisica, Rome (Italy); INFN-Sezione di Roma, Rome (Italy); Universidad de Zaragoza, Laboratorio de Fisica Nuclear y Astroparticulas, Zaragoza (Spain); Moggi, N. [INFN-Sezione di Bologna, Bologna (Italy); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Scienze per la Qualita della Vita, Bologna (Italy); Nones, C. [Service de Physique des Particules, CEA/Saclay, Gif-sur-Yvette (France); Norman, E.B.; Wang, B.S. [Lawrence Livermore National Laboratory, Livermore, CA (United States); University of California, Department of Nuclear Engineering, Berkeley, CA (United States); Ouellet, J.L. [University of California, Department of Physics, Berkeley, CA (United States); Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Massachusetts Institute of Technology, Cambridge, MA (United States); Pagliarone, C.E. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita degli Studi di Cassino e del Lazio Meridionale, Dipartimento di Ingegneria Civile e Meccanica, Cassino (Italy); Sangiorgio, S.; Scielzo, N.D. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Santone, D. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); Universita dell' Aquila, Dipartimento di Scienze Fisiche e Chimiche, L' Aquila (Italy); Singh, V. [University of California, Department of Physics, Berkeley, CA (US); Taffarello, L. [INFN-Sezione di Padova, Padova (IT); Wise, T. [Yale University, Department of Physics, New Haven, CT (US); University of Wisconsin, Department of Physics, Madison, WI (US); Woodcraft, A. [University of Edinburgh, SUPA, Institute for Astronomy, Edinburgh (GB); Zimmermann, S. [Lawrence Berkeley National Laboratory, Engineering Division, Berkeley, CA (US); Zucchelli, S. [INFN-Sezione di Bologna, Bologna (IT); Alma Mater Studiorum-Universita di Bologna, Dipartimento di Fisica e Astronomia, Bologna (IT)

    2017-01-15

    We report on the measurement of the two-neutrino double-beta decay half-life of {sup 130}Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO{sub 2}, the half-life is determined to be T{sub 1/2}{sup 2ν} = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] x 10{sup 20} year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the {sup 130}Te neutrinoless double-beta decay region of interest. (orig.)

  7. The interaction between thermodynamic stability and buried free cysteines in regulating the functional half-life of fibroblast growth factor-1.

    Science.gov (United States)

    Lee, Jihun; Blaber, Michael

    2009-10-16

    Protein biopharmaceuticals are an important and growing area of human therapeutics; however, the intrinsic property of proteins to adopt alternative conformations (such as during protein unfolding and aggregation) presents numerous challenges, limiting their effective application as biopharmaceuticals. Using fibroblast growth factor-1 as model system, we describe a cooperative interaction between the intrinsic property of thermostability and the reactivity of buried free-cysteine residues that can substantially modulate protein functional half-life. A mutational strategy that combines elimination of buried free cysteines and secondary mutations that enhance thermostability to achieve a substantial gain in functional half-life is described. Furthermore, the implementation of this design strategy utilizing stabilizing mutations within the core region resulted in a mutant protein that is essentially indistinguishable from wild type as regard protein surface and solvent structure, thus minimizing the immunogenic potential of the mutations. This design strategy should be generally applicable to soluble globular proteins containing buried free-cysteine residues.

  8. Some problems of parametric neutron activation analysis based on the use of radioactive daughters of longer-lived mothers with low mother/daughter half-life ratios

    International Nuclear Information System (INIS)

    Cohen, I.M.

    2012-01-01

    The theoretical and practical aspects of the use of radioactive daughters originated from the decay of longer-lived radioactive mothers in parametric activation analysis, when the ratio: mother half-life to daughter half-life is less than 10, are discussed. The mother-daughter relationships: 47 Ca/ 47 Sc; 95 Zr/ 95 Nb; 140 Ba/ 140 La; 99 Mo/ 99m Tc and 115 Cd/ 115m In are selected as models for the study. The cases when the radionuclide of interest is formed through both direct and indirect routes are also analyzed. As illustrative example, the direct reaction and the reaction chain: 47 Ti(n,p) 47 Sc/ 46 Ca(n,γ) 47 Ca(β - ) 47 Sc are evaluated with respect to the determination of the elements involved and their reciprocal interferences. (author)

  9. Enhanced infectivity of bluetongue virus in cell culture by centrifugation.

    OpenAIRE

    Sundin, D R; Mecham, J O

    1989-01-01

    The effects of centrifugation of the infection of cell culture with bluetongue virus (BTV) were investigated. Baby hamster kidney cells were infected with BTV with or without centrifugation. Viral antigen was detected by immunofluorescence at 24 h in both centrifuged and noncentrifuged cultures. However, after 24 h of infection, the production of PFU in centrifuged cell cultures was 10- to 20-fold greater than that seen in cultures not centrifuged. In addition, centrifugation enhanced the dir...

  10. Polypeptide synthesis in alphavirus-infected aedes albopictus cells during the establishment of persistent infection

    International Nuclear Information System (INIS)

    Richardson, M.A.; Boulton, R.W.; Raghow, R.S.; Dalgarno, L.

    1980-01-01

    Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cells, RRV reached peak titres at 34-48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and <5 per cent of cells assayed as infected. There was not shutdown of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s).The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persistently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK cells host protein synthesis was severely inhibited and by 9-11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity. (author)

  11. Pile-up corrections for high-precision superallowed β decay half-life measurements via γ-ray photopeak counting

    Science.gov (United States)

    Grinyer, G. F.; Svensson, C. E.; Andreoiu, C.; Andreyev, A. N.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Chakrawarthy, R. S.; Finlay, P.; Garrett, P. E.; Hackman, G.; Hyland, B.; Kulp, W. D.; Leach, K. G.; Leslie, J. R.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Sarazin, F.; Schumaker, M. A.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Williams, S. J.; Wong, J.; Wood, J. L.; Zganjar, E. F.

    2007-09-01

    A general technique that corrects γ-ray gated β decay-curve data for detector pulse pile-up is presented. The method includes corrections for non-zero time-resolution and energy-threshold effects in addition to a special treatment of saturating events due to cosmic rays. This technique is verified through a Monte Carlo simulation and experimental data using radioactive beams of Na26 implanted at the center of the 8π γ-ray spectrometer at the ISAC facility at TRIUMF in Vancouver, Canada. The β-decay half-life of Na26 obtained from counting 1809-keV γ-ray photopeaks emitted by the daughter Mg26 was determined to be T=1.07167±0.00055 s following a 27σ correction for detector pulse pile-up. This result is in excellent agreement with the result of a previous measurement that employed direct β counting and demonstrates the feasibility of high-precision β-decay half-life measurements through the use of high-purity germanium γ-ray detectors. The technique presented here, while motivated by superallowed-Fermi β decay studies, is general and can be used for all half-life determinations (e.g. α-, β-, X-ray, fission) in which a γ-ray photopeak is used to select the decays of a particular isotope.

  12. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  13. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  14. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

    Directory of Open Access Journals (Sweden)

    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  15. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  16. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection.

    Directory of Open Access Journals (Sweden)

    Dominic Paquin-Proulx

    2018-01-01

    Full Text Available Dengue virus (DENV and Zika virus (ZIKV are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome. The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.

  18. NKT cell depletion in humans during early HIV infection.

    Science.gov (United States)

    Fernandez, Caroline S; Kelleher, Anthony D; Finlayson, Robert; Godfrey, Dale I; Kent, Stephen J

    2014-08-01

    Natural killer T (NKT) cells bridge across innate and adaptive immune responses and have an important role in chronic viral infections such as human immunodeficiency virus (HIV). NKT cells are depleted during chronic HIV infection, but the timing, drivers and implications of this NKT cell depletion are poorly understood. We studied human peripheral blood NKT cell levels, phenotype and function in 31 HIV-infected subjects not on antiretroviral treatment from a mean of 4 months to 2 years after HIV infection. We found that peripheral CD4(+) NKT cells were substantially depleted and dysfunctional by 4 months after HIV infection. The depletion of CD4(+) NKT cells was more marked than the depletion of total CD4(+) T cells. Further, the early depletion of NKT cells correlated with CD4(+) T-cell decline, but not HIV viral levels. Levels of activated CD4(+) T cells correlated with the loss of NKT cells. Our studies suggest that the early loss of NKT cells is associated with subsequent immune destruction during HIV infection.

  19. Intracellular Events and Cell Fate in Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Elena Ryabchikova

    2011-08-01

    Full Text Available Marburg and Ebola viruses cause a severe hemorrhagic disease in humans with high fatality rates. Early target cells of filoviruses are monocytes, macrophages, and dendritic cells. The infection spreads to the liver, spleen and later other organs by blood and lymph flow. A hallmark of filovirus infection is the depletion of non-infected lymphocytes; however, the molecular mechanisms leading to the observed bystander lymphocyte apoptosis are poorly understood. Also, there is limited knowledge about the fate of infected cells in filovirus disease. In this review we will explore what is known about the intracellular events leading to virus amplification and cell damage in filovirus infection. Furthermore, we will discuss how cellular dysfunction and cell death may correlate with disease pathogenesis.

  20. Alemtuzumab-induced elimination of HIV-1-infected immune cells.

    Science.gov (United States)

    Ruxrungtham, Kiat; Sirivichayakul, Sunee; Buranapraditkun, Supranee; Krause, Werner

    2016-01-01

    Currently, there is no drug known that is able to eradicate either HIV or HIV-infected host cells. The effectiveness of all available treatments is based on the prevention of viral replication. We investigated whether the monoclonal, CD52 receptor-targeting antibody, alemtuzumab, which is currently approved for the treatment of multiple sclerosis, is able to eliminate HIV-infected immune cells. In blood samples from healthy donors and from HIV-1-infected subjects who were either treatment-naïve or resistant to HAART, we studied whether the CD52 expression on T cells and their subsets (CD3, CD4, CD8), B cells (CD19), dendritic cells (CD123) and monocytes (CD11c) is retained in HIV-1 infection and whether alemtuzumab is able to eradicate infected cells, using four-colour flow cytometry. We found that CD52 expression on immune cells is retained in HIV-1 infection regardless of CD4 cell count, viral load and treatment status, and is amenable to alemtuzumab-induced depletion. For the first time it could be shown in vitro that HIV-1-infected immune cells can be eliminated by using the monoclonal antibody alemtuzumab.

  1. Effects of interferon on cultured cells persistently infected with viruses

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, M

    1986-01-01

    The role of interferon (IFN) in viral persistence at the cellular level was investigated. Two types of persistent infections were chosen. The first type was cell lines which contained hepatitis B virus (HBV) DNA (PLC/PRF/5 and Hep 3B cells) uninfected control hepatoma cells, (Mahlavu, HA22T and Hep G2 cells) or simian virus 40 (SV40) DNA (C2, C6, C11 cells) and control uninfected (CV-1 cells). In the second type of infection Vero cells persistently infected with SSPE or Sendai virus were used. The aim of this work was to determine what effect IFN had in these infections in terms of its antiviral and antiproliferative effects; which of the two major IFN-induced pathways, E enzyme or protein kinase were induced; whether there were any differences in sensitivity to IFN between the DNA and RNA virus persistent infections. The anti-viral effect of IFN was examined by its ability to inhibit Sindbis virus replication using a radioimmunoassay system. The antiproliferative effect of IFN was determined by cell counting and /sup 3/H-thymidine incorporation. The activation of the ribonuclease F, determined by the inhibition of /sup 3/H-leucine incorporation after introduction of 2-5 actin into the cells, was variable, being activated in all cell lines with the exception of the PLC/PRF/5, Hep 3B and Hep G2 cells. Major differences between the two DNA persistent infections and the two RNA persistent infections were found. No correlation was found between the presence of HBV or SV40 persistent infections and the sensitivity of the cell lines to IFN. Both the SSPE and Sendai virus persistent infections were resistant to the antiviral and antiproliferative effect of IFN.

  2. Potential Cellular Signatures of Viral Infections in Human Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    J. Mikovits

    2001-01-01

    Full Text Available Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kapsosi’s Sarcoma -associated Virus (KSHV also known as Human Herpesvirus 8 (HHV8 and Human T cell leukemia virus-1 (HTLV-1. We performed cell-free {\\it in vitro} infection of primary bone marrow derived CD34+ cells using semi-purified HHV8 and a mature IL-2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV-1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two-fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4, cyclin B2, TBP-associated factor, eukaryotic elongation factor and pim 2 were up-regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than two-fold following chronic infection of a mature T cell line with HTLV-1. Of these, only cdc7 was up-regulated more than 3.5 fold. These data may provide insight into cellular signatures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention.

  3. Half-Life of Sulfonylureas in HNF1A and HNF4A Human MODY Patients is not Prolonged as Suggested by the Mouse Hnf1a(-/-) Model.

    Science.gov (United States)

    Urbanova, Jana; Andel, Michal; Potockova, Jana; Klima, Josef; Macek, Jan; Ptacek, Pavel; Mat'oska, Vaclav; Kumstyrova, Tereza; Heneberg, Petr

    2015-01-01

    Sulfonylurea derivatives are widely used for clinical treatment of human subjects with Maturity Onset Diabetes of the Young (MODY) caused by mutations in HNF-1α or HNF-4α despite the mechanism leading to their hypersensitivity is incompletely understood. In Hnf1a(-/-) mice, serum concentrations and half-life of sulfonylurea derivatives are strongly increased. We thus hypothesized that reduced sulfonylurea derivatives clearance stands behind their therapeutic potential in human HNF1A/HNF4A MODY subjects. Single doses of 3 mg glipizide and 5 mg glibenclamide/glyburide were administered sequentially to seven HNF1A/HNF4A MODY subjects and six control individuals matched for their age, BMI and CYP2C9 genotype. Pharmacokinetic (plasma concentration levels, Cmax, tmax, t1/2, AUC) and pharmacodynamic parameters (glycemia, C-peptide and insulin plasma levels) were followed for 24 hours after drug administration. We provide the first evidence on the pharmacokinetics and pharmacodynamics of sulfonylurea derivatives in human MODY subjects. The half-life of glipizide did not change, and reached 3.8±0.7 and 3.7±1.8 h in the MODY and control subjects, respectively. The half-life of glibenclamide was increased only in some MODY subjects (t1/2 9.5±6.7 and 5.0±1.4 h, respectively). Importantly, the intra- individual responses of MODY (but control) subjects to glipizide and glibenclamide treatment were highly correlated. With regards to pharmacodynamics, we observed a differential response of control but not MODY subjects to the doses of glipizide and glibenclamide applied. We rejected the hypothesis that all human MODY-associated mutations in HNF1A / HNF4A induce changes in the pharmacokinetics of sulfonylureas in humans analogically to the Hnf1a(-/-) mouse model.

  4. Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans.

    Science.gov (United States)

    Yaginuma-Sakurai, Kozue; Murata, Katsuyuki; Iwai-Shimada, Miyuki; Nakai, Kunihiko; Kurokawa, Naoyuki; Tatsuta, Nozomi; Satoh, Hiroshi

    2012-02-01

    The hair-to-blood ratio and biological half-life of methylmercury in a one-compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 µg/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 µg/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 ± 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 ± 23 days for blood and 102 ± 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 ± 18 and 64 ± 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one.

  5. CYP2C8 activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe.

    Science.gov (United States)

    Backman, Janne T; Honkalammi, Johanna; Neuvonen, Mikko; Kurkinen, Kaisa J; Tornio, Aleksi; Niemi, Mikko; Neuvonen, Pertti J

    2009-12-01

    Gemfibrozil 1-O-beta-glucuronide is a mechanism-based inhibitor of cytochrome P450 2C8. We studied the recovery of CYP2C8 activity after discontinuation of gemfibrozil treatment using repaglinide as a probe drug, to estimate the in vivo turnover half-life of CYP2C8. In a randomized five-phase crossover study, nine healthy volunteers ingested 0.25 mg of repaglinide alone or after different time intervals after a 3-day treatment with 600 mg of gemfibrozil twice daily. The area under the plasma concentration-time curve (AUC) from time 0 to infinity of repaglinide was 7.6-, 2.9-, 1.4- and 1.0-fold compared with the control phase when it was administered 1, 24, 48, or 96 h after the last gemfibrozil dose, respectively (P gemfibrozil). Thus, a strong CYP2C8 inhibitory effect persisted even after gemfibrozil and gemfibrozil 1-O-beta-glucuronide concentrations had decreased to less than 1% of their maximum (24-h dosing interval). In addition, the metabolite to repaglinide AUC ratios indicated that significant (P gemfibrozil administration. Based on the recovery of repaglinide oral clearance, the in vivo turnover half-life of CYP2C8 was estimated to average 22 +/- 6 h (mean +/- S.D.). In summary, CYP2C8 activity is recovered gradually during days 1 to 4 after gemfibrozil discontinuation, which should be considered when CYP2C8 substrate dosing is planned. The estimated CYP2C8 half-life will be useful for in vitro-in vivo extrapolations of drug-drug interactions involving induction or mechanism-based inhibition of CYP2C8.

  6. The homeostasis of Plasmodium falciparum-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jakob M A Mauritz

    2009-04-01

    Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

  7. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  8. Immune regulation in Chandipura virus infection: characterization of CD4+ T regulatory cells from infected mice

    Directory of Open Access Journals (Sweden)

    Shahir Prajakta

    2011-05-01

    Full Text Available Abstract Back ground Chandipura virus produces acute infection in mice. During infection drastic reduction of CD4+, CD8+ and CD19 + cell was noticed. Depletion of lymphocytes also noticed in spleen. The reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. There are several mechanisms like generation of regulatory cells, activation induced cell death (ACID etc were indicated to control the activation and maintain cellular homeostasis. Role of regulatory cells in homeostasis has been described in several viral diseases. This study was undertaken to characterize CD4+T regulatory cells from the infected mice. Method In this study we purified the CD4+ T cells from Chandipura virus infected susceptible Balb/c mice. CD4+ T regulatory cells were identified by expression of cell surface markers CD25, CD127 and CTLA-4 and intracellular markers Foxp3, IL-10 and TGF-beta. Antigen specificity and ability to suppress the proliferation of other lymphocytes were studied in vitro by purified CD4+CD25+T regulatory cells from infected mice. The proliferation was calculated by proliferation module of Flow Jo software. Expression of death receptors on regulatory cells were studied by flowcytometer. Results The CD4+ T cells isolated from infected mice expressed characteristic markers of regulatory phenotype at all post infective hours tested. The CD4+ T regulatory cells were proliferated when stimulated with Chandipura virus antigen. The regulatory cells did not suppress the proliferation of splenocytes stimulated with anti CD3 antibody when co cultured with them. Interesting observation was, while purification of CD4+ T cells by negative selection, the population of cells negative for CD4 also co purified along with CD4+ T cell. Flow cytometry analysis and light microscopy revealed that CD4 negative cells were of different size and shape (atypical compared to the normal lymphocytes. Greater percentage of

  9. Nipah virus infection and glycoprotein targeting in endothelial cells

    Directory of Open Access Journals (Sweden)

    Maisner Andrea

    2010-11-01

    Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

  10. Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells.

    Science.gov (United States)

    Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha

    2017-09-01

    Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood. Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains. Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P[8] and G2P[4] through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells). Oligosaccharides were added at different time points in the infectivity assays. Infections in the absence of oligosaccharides served as controls. Results: When compared with infections in the absence of glycans, all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain-specific differences in effects were observed. Compared with control infections, the maximum reduction in G1P[8] infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific oligosaccharides to infant formula may confer these benefits to formula-fed infants. © 2017 American Society for Nutrition.

  11. In vivo infection of IgG-containing cells by Jembrana disease virus during acute infection

    International Nuclear Information System (INIS)

    Desport, Moira; Tenaya, I.W. Masa; McLachlan, Alexander; McNab, Tegan J.; Rachmat, Judhi; Hartaningsih, Nining; Wilcox, Graham E.

    2009-01-01

    Jembrana disease virus (JDV) is an unusual bovine lentivirus which causes a non-follicular proliferation of lymphocytes, a transient immunosuppression and a delayed humoral response in infected Bali cattle in Indonesia. A double-immunofluorescent labeling method was developed to identify the subset of mononuclear cells in which the viral capsid protein could be detected. Viral antigen was present in pleomorphic centroblast-like cells which were identified as IgG-containing cells, including plasma cells, in lymphoid tissues. There was no evidence of infection of CD3 + T-cells or MAC387 + monocytes in tissues but large vacuolated cells with a macrophage-like morphology in the lung were found to contain viral antigen although they could not be shown conclusively to be infected. The tropism of JDV for mature IgG-containing cells may be relevant to understanding the pathogenesis of Jembrana disease, the delayed antibody responses and the genetic composition of this atypical lentivirus.

  12. The involvement of plasmacytoid cells in HIV infection and pathogenesis.

    Science.gov (United States)

    Aiello, Alessandra; Giannessi, Flavia; Percario, Zulema A; Affabris, Elisabetta

    2018-04-01

    Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that are specialized in type I interferon (IFN) production. pDCs are key players in the antiviral immune response and serve as bridge between innate and adaptive immunity. Although pDCs do not represent the main reservoir of the Human Immunodeficiency Virus (HIV), they are a crucial subset in HIV infection as they influence viral transmission, target cell infection and antigen presentation. pDCs act as inflammatory and immunosuppressive cells, thus contributing to HIV disease progression. This review provides a state of art analysis of the interactions between HIV and pDCs and their potential roles in HIV transmission, chronic immune activation and immunosuppression. A thorough understanding of the roles of pDCs in HIV infection will help to improve therapeutic strategies to fight HIV infection, and will further increase our knowledge on this important immune cell subset. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stephen H-F Macdonald

    Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

  14. New AMS method to measure the atom ratio {sup 146}Sm/{sup 147}Sm for a half-life determination of {sup 146}Sm

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, N. [Tandem Accelerator Complex, Research Facility Center for Science and Technology, University of Tsukuba (Japan); Paul, M., E-mail: paul@vms.huji.ac.il [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Alcorta, M. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Bowers, M.; Collon, P. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); Deibel, C.M. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Joint Institute for Nuclear Astrophysics, Michigan State University, East Lansing, MI 46624 (United States); DiGiovine, B. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Goriely, S. [Universite Libre de Bruxelles, CP-226, Brussels 1050 (Belgium); Greene, J.P.; Henderson, D.J.; Jiang, C.L. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Kashiv, Y. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); Kay, B.P.; Lee, H.Y.; Marley, S.T. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Nakanishi, T. [Faculty of Chemistry, Institute of Science and Engineering, Kanazawa University (Japan); Pardo, R.C.; Patel, N.; Rehm, K.E. [Physics Division, Argonne National Laboratory, Argonne, IL 60439 (United States); Robertson, D. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556-5670 (United States); and others

    2013-01-15

    The extinct p-process nuclide {sup 146}Sm (t{sub 1/2} = 103 {+-} 5 Myr) is known to have been present in the Early-Solar System and has been proposed as an astrophysical chronometer. {sup 146}Sm is also intensely used to date meteorite and planetary differentiation processes, enhancing the importance of an accurate knowledge of the {sup 146}Sm half-life. We are engaged in a new determination of the {sup 146}Sm half-life in which the {sup 146}Sm/{sup 147}Sm atom ratio is determined by accelerator mass spectrometry at the ATLAS facility of Argonne National Laboratory. In order to reduce systematic errors in the AMS determination of the {sup 146}Sm/{sup 147}Sm ratios (in the range of 10{sup -7}-10{sup -9}), {sup 146}Sm and {sup 147}Sm ions were alternately counted in the same detector in the focal plane of a gas-filled magnet, respectively in continuous-wave and attenuated mode. Quantitative attenuation is obtained with the 12 MHz pulsed and ns-bunched ATLAS beam by chopping beam pulses with an RF sweeper in a ratio (digitally determined) down to 1:10{sup 6}. The experiments and preliminary results are discussed.

  15. Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

    Science.gov (United States)

    Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

    2018-01-01

    SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

  16. Ureaplasma parvum infection alters filamin a dynamics in host cells

    Directory of Open Access Journals (Sweden)

    Brown Mary B

    2011-04-01

    Full Text Available Abstract Background Ureaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasmas can produce asymptomatic infections or disease characterized by an exaggerated inflammatory response. Most investigations have focused on elucidating the pathogenic potential of Ureaplasma species, but little attention has been paid to understanding the mechanisms by which these organisms are capable of establishing asymptomatic infection. Methods We employed differential proteome profiling of bladder tissues from rats experimentally infected with U. parvum in order to identify host cell processes perturbed by colonization with the microbe. Tissues were grouped into four categories: sham inoculated controls, animals that spontaneously cleared infection, asymptomatic urinary tract infection (UTI, and complicated UTI. One protein that was perturbed by infection (filamin A was used to further elucidate the mechanism of U. parvum-induced disruption in human benign prostate cells (BPH-1. BPH-1 cells were evaluated by confocal microscopy, immunoblotting and ELISA. Results Bladder tissue from animals actively colonized with U. parvum displayed significant alterations in actin binding proteins (profilin 1, vinculin, α actinin, and filamin A that regulate both actin polymerization and cell cytoskeletal function pertaining to focal adhesion formation and signal transduction (Fisher's exact test, P U. parvum perturbed the regulation of filamin A. Specifically, infected BPH-1 cells exhibited a significant increase in filamin A phosphorylated at serine2152 (P ≤ 0.01, which correlated with impaired proteolysis of the protein and its normal intracellular distribution. Conclusion Filamin A dynamics were perturbed in both models of infection. Phosphorylation of filamin A occurs in response to various cell signaling cascades that regulate cell motility, differentiation, apoptosis and inflammation. Thus, this phenomenon may be a useful

  17. Selective receptor expression restricts Nipah virus infection of endothelial cells

    Directory of Open Access Journals (Sweden)

    Diederich Sandra

    2008-11-01

    Full Text Available Abstract Nipah virus (NiV is a highly pathogenic paramyxovirus that causes severe diseases in animals and humans. Endothelial cell (EC infection is an established hallmark of NiV infection in vivo. Despite systemic virus spread via the vascular system, EC in brain and lung are preferentially infected whereas EC in other organs are less affected. As in vivo, we found differences in the infection of EC in cell culture. Only brain-derived primary or immortalized EC were found to be permissive to NiV infection. Using a replication-independent fusion assay, we could show that the lack of infection in non-brain EC was due to a lack of receptor expression. The NiV entry receptors ephrinB2 (EB2 or ephrinB3 were only expressed in brain endothelia. The finding that EB2 expression in previously non-permissive aortic EC rendered the cells permissive to infection then demonstrated that EB2 is not only necessary but also sufficient to allow the establishment of a productive NiV infection. This strongly suggests that limitations in receptor expression restrict virus entry in certain EC subsets in vivo, and are thus responsible for the differences in EC tropism observed in human and animal NiV infections.

  18. Transfusion associated hepatitis B virus infection among sickle cell ...

    African Journals Online (AJOL)

    Background: Transfusion of blood products is a recognised way of transmitting infections particularly viruses. The extent to which blood transfusion contributes to hepatitis B virus (HBV) infections in transfused patients with sickle cell anaemia (SCA) has been found to be 20% in Lagos, Nigeria. Mamman in Zaria however ...

  19. Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

    DEFF Research Database (Denmark)

    Ibitokou, Samad; Oesterholt, Mayke; Brutus, Laurent

    2012-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective ...

  20. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    Science.gov (United States)

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Infection of endothelial cells by common human viruses.

    Science.gov (United States)

    Friedman, H M

    1989-01-01

    Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

  2. Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Mamo Gezahagne

    2011-07-01

    Full Text Available Abstract Background Dendritic cells (DCs can take up an array of different antigens, including microorganisms which they can process and present more effectively than any other antigen presenting cell. However, whether the interaction between the human DC and Mycobacterium tuberculosis represents a defense mechanism by the invaded host, or helping the invader to evade the defense mechanism of the host is still not clearly understood. Findings To analyze the interactions between M. tuberculosis and immune cells, human peripheral blood monocyte-derived immature DCs were infected with M. tuberculosis H37Rv wild type strain and flow cytometry was used to analyse cell surface expression markers. The ability of the M. tuberculosis infected DC to induce T cell proliferation using 5 and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE dilution technique was also investigated. DCs were found to internalize the mycobacteria and show dose dependent infection and necrosis with different multiplicity of infection. Flow cytometry analysis of cell surface expression markers CD40, CD54, CD80, CD83, CD86 and HLA DR in infected DC revealed significant (p M. tuberculosis in comparison to immature DC with no stimulation. Lipopolysaccharide (LPS from Salmonella abortus equi, a known DC maturation agent, was used as a positive control and showed a comparable up regulation of cell surface markers as observed with M. tuberculosis infected DC. It was revealed that the M. tuberculosis infected DC induced T cell proliferation. Conclusion These data clearly demonstrate that M. tuberculosis induces activation and maturation of human monocyte-derived immature DC as well as induces T cell proliferation in vitro.

  3. Invariant NKT cells: regulation and function during viral infection.

    Directory of Open Access Journals (Sweden)

    Jennifer A Juno

    Full Text Available Natural killer T cells (NKT cells represent a subset of T lymphocytes that express natural killer (NK cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT, express a highly restricted T cell receptor (TCR and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

  4. Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

    LENUS (Irish Health Repository)

    Ryan, Ruth CM

    2011-10-24

    Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3\\/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.

  5. Purification of a 166mHo solution by successive high-performance liquid chromatography and gravitational chromatography for half-life determination

    International Nuclear Information System (INIS)

    Florence Gueguen; Helene Isnard; Carole Bresson; Celine Caussignac; Guillaume Stadelmann; Anthony Nonell; Sebastien Mialle; Karsten Kossert; Frederic Chartier

    2014-01-01

    A methodology to purify a 166m Ho solution has been developed by a combination of activity and mass concentration measurements in order to further determine the 166m Ho half-life. The isobaric interference at m/q ≃ 166 requires Ho purification from non-natural Er with a high purification degree due to the large amount of Ho as opposed to Er. The Ho/Er separation was achieved using high-performance liquid chromatography on a semi-preparative column followed by purification on gravitational chromatography. The efficiency of the separation was evaluated after precise determination of the Er isotopic composition. The purification methodology enabled to separate Ho from Er. (author)

  6. The short half-life descendents from radon measured in Sao Jose dos Campos and Cachoeira Paulista, Brazil, and its correlation with meteorological data

    International Nuclear Information System (INIS)

    Andrade Marinho, E.V. de.

    1985-09-01

    The correlations between the activity of the short half-life radon decay products in the low atmosphere and the meterological parameters, measuring the atmospheric polonium 214 are studied. The aerosols were collected on membrane filters and analysed by alpha spectrometry. Measurements have been made in Sao Jose dos Campos and Cachoeira Paulista, in Brazil. At S. Jose dos Campos the influence of the pluviometry on the concentration of atmospheric Po 214 has been analysed, showing that high activity correspond to low pluviometry and inversely, low activities correspond to high pluviometry. At Cachoeira Paulista, the variation in the atmospheric Po 214 activity in corresation with the air stability, measured, showing the accumulation of radioactive aerosols during the greater stability in the the lower atmospheric layers, was studied. (author) [pt

  7. The analysis of predictability of α-decay half-life formulae and the α partial half-lives of some exotic nuclei

    International Nuclear Information System (INIS)

    Dasgupta-Schubert, N.; Reyes, M.A.; Tamez, V.A.

    2009-01-01

    The predictabilities of the three α-decay half-life formulae, the Royer GLDM, the Viola-Seaborg and the Sobiczewski-Parkhomenko formulae, have been evaluated by developing a method based on the ansatz of standard experimental benchmarking. The coefficients of each formula were re-derived using the reliable data of the α -standards nuclei. The modified formulae that resulted were used to evaluate the accuracies of the formulae towards the prediction of half-lives of a set of nuclides with well-studied α spectroscopic data as well as a set of exotic α emitters. Further, a simple linear optimisation of the modified formulae allowed adjustments for the insufficient statistics of the primary data set without changing the modified formulae. While the three modified formulae showed equivalent results for all the medium heavy nuclei except the odd-odd, the modified GLDM showed relatively the best figures of merit for the odd-odd and superheavy nuclides. (orig.)

  8. Half-life Measurements of {sup 6}He, {sup 16}N, {sup 19}O, {sup 20}F, {sup 28}Al, {sup 77m}Se and {sup 1}

    Energy Technology Data Exchange (ETDEWEB)

    Konijn, J; Malmskog, S

    1962-06-15

    The half-life of different isotopes, activated by neutrons in the reactor R2-0 by means of a pneumatic rabbit, have been measured with a pulse height analyzer working in its multiscale mode of operation. A Nal(Tl)-scintillation spectrometer was used as detector. Least squares analysis calculated by the Mercury computer were performed for each measurement. The following weighted mean values of the half-lives are obtained {sup 6}He: 0.862 {+-} 0.017 sec.; {sup 16}N: 7.31 {+-} 0.04 sec.; {sup 19}O: 29.1 {+-} 0.3 sec.; {sup 20}F: 11.56 {+-} 0.05 sec.; {sup 28}Al: 2.31 {+-} 0.01 min.; {sup 77m}Se: 18.83 - 0.04 sec.; and {sup 110}Ag: 24.42 {+-} 0.14 sec.

  9. The effective and environmental half-life of {sup 137}Cs at Coral Islands at the former US nuclear test site

    Energy Technology Data Exchange (ETDEWEB)

    Robison, William L. E-mail: robison1@llnl.gov; Conrado, Cynthia L.; Bogen, Kenneth T.; Stoker, A. Carol

    2003-07-01

    The United States (US) conducted nuclear weapons testing from 1946 to 1958 at Bikini and Enewetak Atolls in the northern Marshall Islands. Based on previous detailed dose assessments for Bikini, Enewetak, Rongelap, and Utirik Atolls over a period of 28 years, cesium-137 ({sup 137}Cs) at Bikini Atoll contributes about 85-89% of the total estimated dose through the terrestrial food chain as a result of uptake of {sup 137}Cs by food crops. The estimated integral 30, 50, and 70-year doses were based on the radiological decay of {sup 137}Cs (30-year half-life) and other radionuclides. However, there is a continuing inventory of {sup 137}Cs and {sup 90}Sr in the fresh water portion of the groundwater at all contaminated atolls even though the turnover rate of the fresh groundwater is about 5 years. This is evidence that a portion of the soluble fraction of {sup 137}Cs and {sup 90}Sr inventory in the soil is lost by transport to groundwater when rainfall is heavy enough to cause recharge of the lens, resulting in loss of {sup 137}Cs from the soil column and root zone of the plants. This loss is in addition to that caused by radioactive decay. The effective rate of loss was determined by two methods: (1) indirectly, from time-dependent studies of the {sup 137}Cs concentration in leaves of Pisonia grandis, Guettarda specosia, Tournefortia argentea (also called Messerschmidia), Scaevola taccada, and fruit from Pandanus and coconut trees (Cocos nucifera L.), and (2) more directly, by evaluating the {sup 137}Cs/{sup 90}Sr ratios at Bikini Atoll. The mean (and its lower and upper 95% confidence limits) for effective half-life and for environmental-loss half-life (ELH) based on all the trees studied on Rongelap, Bikini, and Enewetak Atolls are 8.5 years (8.0 years, 9.8 years), and 12 years (11 years, 15 years), respectively. The ELH based on the {sup 137}Cs/{sup 90}Sr ratios in soil in 1987 relative to the{sup 137}Cs/{sup 90}Sr ratios at the time of deposition in 1954 is less

  10. Regulation of NKT Cell Localization in Homeostasis and Infection

    Science.gov (United States)

    Slauenwhite, Drew; Johnston, Brent

    2015-01-01

    Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection. PMID:26074921

  11. Regulation of NKT Cell Localization in Homeostasis and Infection.

    Science.gov (United States)

    Slauenwhite, Drew; Johnston, Brent

    2015-01-01

    Natural killer T (NKT) cells are a specialized subset of T lymphocytes that regulate immune responses in the context of autoimmunity, cancer, and microbial infection. Lipid antigens derived from bacteria, parasites, and fungi can be presented by CD1d molecules and recognized by the canonical T cell receptors on NKT cells. Alternatively, NKT cells can be activated through recognition of self-lipids and/or pro-inflammatory cytokines generated during infection. Unlike conventional T cells, only a small subset of NKT cells traffic through the lymph nodes under homeostatic conditions, with the largest NKT cell populations localizing to the liver, lungs, spleen, and bone marrow. This is thought to be mediated by differences in chemokine receptor expression profiles. However, the impact of infection on the tissue localization and function of NKT remains largely unstudied. This review focuses on the mechanisms mediating the establishment of peripheral NKT cell populations during homeostasis and how tissue localization of NKT cells is affected during infection.

  12. TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

    Science.gov (United States)

    Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

    2017-01-15

    Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope. TIM family proteins were recently found to enhance infections by many different viruses, including several members of the Flaviviridae family. However, their importance in HCV infection has not previously been examined experimentally. The TIM family proteins include three members in humans: TIM-1, TIM-3, and TIM-4. The findings derived from our studies demonstrate that TIM-1, but not TIM-3 or TIM-4, promotes HCV infection by functioning as an HCV attachment factor. Knockout of the TIM-1 gene resulted in a remarkable reduction of HCV cell attachment and infection. PS-containing liposomes blocked HCV cell attachment and subsequent HCV infection. HCV particles could also be precipitated with a PS-specific monoclonal antibody. These findings suggest that TIM-1

  13. Investigation concerning the relative formation rate and half-life time of short-lived nuclides with a fast conveyor tube system

    International Nuclear Information System (INIS)

    Kreiner, H.J.

    1976-01-01

    Since the installation of the 'Ultrafast Rabbit System' at the FRN in end of 1974, some research was started concerning the possibility of neutron activation analysis of short-lived nuclides (0.02 1/2 < 1 s) and measurements of short-lived fission products of U-235 and Pu-239. One of the results of the investigations is a more exact gamma-energy determination of the 0.8 s Cl-38m with 671.33 keV. In NAA it was possible to reach a sensitivity for lead and boron near 2 μg per sample respectively 10 ppm. In measurements of light fission products 0.1 - 8s after a pulse irradiation some differences of the relative formation rate and half-life in the region of A approximately 100 were found in comparison to literature. For example a strong build-up could be seen measuring the gamma-energy of 276.1 keV that belongs to Nb-101. Therefore we suppose the existence of an isomeric state of Nb-101. In comparison to our own results of yield ratio of the Pu- and U-fission products a good agreement with known data was found. Furthermore the measuring method gives the possibility of coordination of unknown gamma-lines to nuclides using the rate of formation, the half-life, the yield ratio between U and Pu and the build-up factor. That could be verified in some cases, e.g. Nb-103 and Sr-96. (author)

  14. Study of niobium isotopes having excess neutrons and a short half-life; Etude des isotopes du niobium excedentaires en neutrons et de courte periode

    Energy Technology Data Exchange (ETDEWEB)

    Huebenthal, K [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1968-02-01

    By irradiating Mo with 14 MeV neutrons isomers have been found for {sup 98}Nb (2.8 s half-life) {sup 99}Nb (9 s) and {sup 100}Nb (2.4 s). No isomer of this type seems to exist for {sup 96}Nb. Rapid separation methods are developed for isolating {sup 98}Zr from fission products, and for separating Zr and Nb. The half-life of {sup 98}Zr is measured (31 s) and the formation of {sup 98}Nb (2.8 s) from {sup 98}Zr (31 s) is shown by milking. Rough {beta} and {gamma} measurements of these nuclei are described. The {gamma} spectrum of {sup 98}Nb (51 mn) is studied with a high-resolution Ge/Li - detector. (authors) [French] Des irradiations des isotopes de molybdene avec des neutrons de 14 MeV ont mis en evidence l'existence des isomeres de {sup 98}Nb (periode 2.8 s) {sup 99}Nb (9 s) et {sup 100}Nb (2.4 s). Pour le {sup 96}Nb un isomere de ce type ne semble pas exister. Des methodes rapides de separation sont mises au point pour isoler le zirconium 98 des produits de fission, et pour separer ensuite le niobium du zirconium. La periode du {sup 98}Zr est de 3l s, et on demontre la formation du {sup 98}Nb (2.8 s) a partir du Zr (31 s). Ces corps sont etudies sommairement en spectroscopie {beta} et {gamma}. Le spectre gamma de {sup 98}Nb (periode 51 mn) est etudie avec un detecteur Ge/Li de haute resolution. (auteurs)

  15. Apoptosis transcriptional mechanism of feline infectious peritonitis virus infected cells.

    Science.gov (United States)

    Shuid, Ahmad Naqib; Safi, Nikoo; Haghani, Amin; Mehrbod, Parvaneh; Haron, Mohd Syamsul Reza; Tan, Sheau Wei; Omar, Abdul Rahman

    2015-11-01

    Apoptosis has been postulated to play an important role during feline infectious peritonitis virus (FIPV) infection; however, its mechanism is not well characterized. This study is focused on apoptosis and transcriptional profiling of FIPV-infected cells following in vitro infection of CRFK cells with FIPV 79-1146 WSU. Flow cytometry was used to determine mode of cell death in first 42 h post infection (hpi). FIPV infected cells underwent early apoptosis at 9 hpi (p apoptosis at 12 hpi (p apoptosis cluster (80 down-regulated and 51 up-regulated) along with increase of apoptosis, p53, p38 MAPK, VEGF and chemokines/cytokines signaling pathways were probably involved in apoptosis process. Six of the de-regulated genes expression (RASSF1, BATF2, MAGEB16, PDCD5, TNFα and TRAF2) and TNFα protein concentration were analyzed by RT-qPCR and ELISA, respectively, at different time-points. Up-regulations of both pro-apoptotic (i.e. PDCD5) and anti-apoptotic (i.e. TRAF2) were detected from first hpi and continuing to deregulate during apoptosis process in the infected cells.

  16. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  17. Dynamics of NKT-Cell Responses to Chlamydial Infection.

    Science.gov (United States)

    Shekhar, Sudhanshu; Joyee, Antony George; Yang, Xi

    2015-01-01

    Natural killer T (NKT) cells have gained great attention owing to their critical functional roles in immunity to various pathogens. In this review, we provide an overview of the current knowledge on the role of NKT cells in host defense against and pathogenesis due to Chlamydia, which is an intracellular bacterial pathogen that poses a threat to the public health worldwide. Accumulating evidence has demonstrated that NKT cells, particularly invariant NKT (iNKT) cells, play a crucial role in host defense against chlamydial infections, especially in C. pneumoniae infection. iNKT cells can promote type-1 protective responses to C. pneumoniae by inducing enhanced production of IL-12 by dendritic cells (DCs), in particular CD8α+ DCs, which promote the differentiation of naive T cells into protective IFN-γ-producing Th1/Tc1 type CD4+/CD8+ T cells. This iNKT-cell-mediated modulation of DC function is largely dependent upon CD40-CD40L interaction, IFN-γ production, and cell-to-cell contact. In addition, iNKT cells modulate the function of natural killer cells. NKT cells may be also involved in the pathogenesis of some chlamydial diseases by inducing different patterns of cytokine production. A better understanding of NKT-cell biology will enable us to rationally design prophylactic and therapeutic tools to combat infectious diseases.

  18. Human neuronal cell protein responses to Nipah virus infection

    Directory of Open Access Journals (Sweden)

    Hassan Sharifah

    2007-06-01

    Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

  19. Apoptosis in HEp-2 cells infected with Ureaplasma diversum.

    Science.gov (United States)

    Amorim, Aline Teixeira; Marques, Lucas Miranda; Santos, Angelita Maria Oliveira Gusmão; Martins, Hellen Braga; Barbosa, Maysa Santos; Rezende, Izadora Souza; Andrade, Ewerton Ferraz; Campos, Guilherme Barreto; Lobão, Tássia Neves; Cortez, Beatriz Araujo; Monezi, Telma Alvez; Machado-Santelli, Glaucia Maria; Timenetsky, Jorge

    2014-09-04

    Bacterial pathogens have many strategies for infecting and persisting in host cells. Adhesion, invasion and intracellular life are important features in the biology of mollicutes. The intracellular location of Ureaplasma diversum may trigger disturbances in the host cell. This includes activation or inhibition of pro and anti-apoptotic factors, which facilitate the development of host damage. The aim of the present study was to associate U. diversum infection in HEp-2 cells and apoptosis induction. Cells were infected for 72hs with four U. diversum clinical isolates and an ATCC strain. The U. diversum invasion was analyzed by Confocal Laser Scanning Microscopy and gentamicin invasion assay. The apoptosis was evaluated using pro-apoptotic and anti-apoptotic gene expression, and FITC Annexin V/Dead Cell Apoptosis Kit. The number of internalized ureaplasma in HEp-2 cells increased significantly throughout the infection. The flow cytometry analysis with fluorochromes to detect membrane depolarization and gene expression for caspase 2, 3 and 9 increased in infected cells after 24 hours. However, after 72 hours a considerable decrease of apoptotic cells was observed. The data suggests that apoptosis may be initially induced by some isolates in association with HEp-2 cells, but over time, there was no evidence of apoptosis in the presence of ureaplasma and HEp-2 cells. The initial increase and then decrease in apoptosis could be related to bacterial pathogen-associated molecular pattern (PAMPS). Moreover, the isolates of U. diversum presented differences in the studied parameters for apoptosis. It was also observed that the amount of microorganisms was not proportional to the induction of apoptosis in HEp-2 cells.

  20. Hepatitis B Virus Infection In Patients With Homozygous Sickle Cell ...

    African Journals Online (AJOL)

    Nnebe-Agumadu U H, and Abiodun P O. Hepatitis B Virus Infection in Patients with Homozygous Sickle Cell Disease (HbSS): Need for Intervention. Annals Biomedical Sciences 2002; 1:79-87. This is a prospective study of 213 patients with sickle cell anaemia (SCA) (112 males and 101 females) aged 6 months to 18 years ...

  1. Vaccination against feline immunodeficiency virus using fixed infected cells

    NARCIS (Netherlands)

    Horzinek, M.C.; Verschoor, E.J.; Vliet, A.L.W. van; Egberink, H.F.; Hesselink, W.; Alphen, W.E. van; Joosten, I.; Boog, C.J.P.; Ronde, A. de

    1995-01-01

    Crandell feline kidney cells and feline thymocytes, either feline immunodeficiency virus (FIV) infected or uninfected, were fixed with paraformaldehyde and used to vaccinate cats. The cells were mixed with a 30:70 water/mineral oil emulsion containing 250 mu g ml−1 N-acetyl-d-glucosaminyl-beta-(1

  2. Electron Microscopy of Ebola Virus-Infected Cells.

    Science.gov (United States)

    Noda, Takeshi

    2017-01-01

    Ebola virus (EBOV) replicates in host cells, where both viral and cellular components show morphological changes during the process of viral replication from entry to budding. These steps in the replication cycle can be studied using electron microscopy (EM), including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), which is one of the most useful methods for visualizing EBOV particles and EBOV-infected cells at the ultrastructural level. This chapter describes conventional methods for EM sample preparation of cultured cells infected with EBOV.

  3. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    2009-09-01

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  4. The CD8 T Cell Response to Respiratory Virus Infections.

    Science.gov (United States)

    Schmidt, Megan E; Varga, Steven M

    2018-01-01

    Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.

  5. Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

    International Nuclear Information System (INIS)

    Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

    2003-01-01

    Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

  6. Activation of Natural Killer cells during microbial infections

    Directory of Open Access Journals (Sweden)

    Amir eHorowitz

    2012-01-01

    Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.

  7. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    Science.gov (United States)

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  8. Differential pulmonic NK and NKT cell responses in Schistosoma japonicum-infected mice.

    Science.gov (United States)

    Cha, Hefei; Qin, Wenjuan; Yang, Quan; Xie, Hongyan; Qu, Jiale; Wang, Mei; Chen, Daixiong; Wang, Fang; Dong, Nuo; Chen, Longhua; Huang, Jun

    2017-02-01

    Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas. Moreover, flow cytometry revealed that the percentage and number of pulmonic NK cells in S. japonicum-infected mice were significantly increased (P cell number of NKT cells were decreased compared to those of normal mice (P NKT cells was increased after infection (P NKT cells (P cells (P NKT cells significantly increased (P NKT cells (P NKT cell activation during S. japonicum infection.

  9. Infection and Proliferation of Giant Viruses in Amoeba Cells.

    Science.gov (United States)

    Takemura, Masaharu

    2016-01-01

    Acanthamoeba polyphaga mimivirus, the first discovered giant virus with genome size and particle size much larger than previously discovered viruses, possesses several genes for translation and CRISPER Cas system-like defense mechanism against virophages, which co-infect amoeba cells with the giant virus and which inhibit giant virus proliferation. Mimiviruses infect amoeba cells by phagocytosis and release their DNA into amoeba cytoplasm through their stargate structure. After infection, giant virion factories (VFs) form in amoeba cytoplasm, followed by DNA replication and particle formation at peripheral regions of VF. Marseilleviruses, the smallest giant viruses, infect amoeba cells by phagocytosis or endocytosis, form larger VF than Mimivirus's VF in amoeba cytoplasm, and replicate their particles. Pandoraviruses found in 2013 have the largest genome size and particle size among all viruses ever found. Pandoraviruses infect amoeba cells by phagocytosis and release their DNA into amoeba cytoplasm through their mouth-like apical pores. The proliferation of Pandoraviruses occurs along with nucleus disruption. New virions form at the periphery of the region formerly occupied by the amoeba cell nucleus.

  10. Changes in cell adhesion molecule expression on T cells associated with systemic virus infection

    DEFF Research Database (Denmark)

    Andersson, E C; Christensen, Jan Pravsgaard; Marker, O

    1994-01-01

    -4, LFA-1, and ICAM-1, are up-regulated on CD8+ cells, whereas the lymph node homing receptor MEL-14 is down-regulated during the infection; only marginal changes were observed for CD4+ cells. Basically similar but less marked results were obtained in mice infected with Pichinde virus. Further...

  11. IL-15 STIMULATED NATURAL KILLER CELLS CLEAR HIV-1 INFECTED CELLS FOLLOWING LATENCY REVERSAL EX VIVO.

    Science.gov (United States)

    Garrido, Carolina; Abad-Fernandez, Maria; Tuyishime, Marina; Pollara, Justin J; Ferrari, Guido; Soriano-Sarabia, Natalia; Margolis, David M

    2018-03-28

    Current efforts towards HIV eradication include approaches to augment immune recognition and elimination of persistently infected cells following latency reversal. Natural killer (NK) cells, the main effectors of the innate immune system, recognize and clear targets using different mechanisms than CD8 + T cells, offering an alternative or complementary approach for HIV clearance strategies. We assessed the impact of IL-15 treatment on NK cell function and the potential of stimulated NK cells to clear the HIV reservoir. We measured NK cell receptor expression, antibody-dependent cell-dependent cytotoxicity (ADCC), cytotoxicity, IFN-γ production and antiviral activity in autologous HIV replication systems. All NK cell functions were uniformly improved by IL-15, and more importantly, IL-15-treated NK cells were able to clear latently HIV infected cells after exposure to vorinostat, a clinically relevant latency reversing agent. We also demonstrate that NK cells from HIV infected individuals aviremic on antiretroviral therapy can be efficiently stimulated with IL-15. Our work opens a promising line of investigation towards future immunotherapies to clear persistent HIV infection using NK cells. IMPORTANCE In the search for an HIV cure, strategies to enhance immune function to allow recognition and clearance of HIV infected cells following latency reversal are being evaluated. Natural killer (NK) cells possess characteristics that can be exploited for immunotherapy against persistent HIV infection. We demonstrate that NK cells from HIV-positive donors can be strongly stimulated with IL-15, improving their antiviral and cytotoxic potential, and more importantly, clearing HIV infected cells after latency reversal with a clinically relevant drug. Our results encourage further investigation to design NK cell-based immunotherapies to achieve HIV eradication. Copyright © 2018 American Society for Microbiology.

  12. Roles for Endothelial Cells in Dengue Virus Infection

    Directory of Open Access Journals (Sweden)

    Nadine A. Dalrymple

    2012-01-01

    Full Text Available Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF and dengue shock syndrome (DSS. The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

  13. Group 1 innate lymphoid cells in Toxoplasma gondii infection.

    Science.gov (United States)

    Dunay, I R; Diefenbach, A

    2018-02-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 + cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets. © 2018 John Wiley & Sons Ltd.

  14. Ebola virus infection induces irregular dendritic cell gene expression.

    Science.gov (United States)

    Melanson, Vanessa R; Kalina, Warren V; Williams, Priscilla

    2015-02-01

    Filoviruses subvert the human immune system in part by infecting and replicating in dendritic cells (DCs). Using gene arrays, a phenotypic profile of filovirus infection in human monocyte-derived DCs was assessed. Monocytes from human donors were cultured in GM-CSF and IL-4 and were infected with Ebola virus Kikwit variant for up to 48 h. Extracted DC RNA was analyzed on SuperArray's Dendritic and Antigen Presenting Cell Oligo GEArray and compared to uninfected controls. Infected DCs exhibited increased expression of cytokine, chemokine, antiviral, and anti-apoptotic genes not seen in uninfected controls. Significant increases of intracellular antiviral and MHC I and II genes were also noted in EBOV-infected DCs. However, infected DCs failed to show any significant difference in co-stimulatory T-cell gene expression from uninfected DCs. Moreover, several chemokine genes were activated, but there was sparse expression of chemokine receptors that enabled activated DCs to home to lymph nodes. Overall, statistically significant expression of several intracellular antiviral genes was noted, which may limit viral load but fails to stop replication. EBOV gene expression profiling is of vital importance in understanding pathogenesis and devising novel therapeutic treatments such as small-molecule inhibitors.

  15. Determination of half life of the pesticides chlorpyrifos (14C) in an agricultural soil of the VI region by means of the using isotopic techniques

    International Nuclear Information System (INIS)

    Camarda Rojas, Gabriela Paz

    2005-01-01

    Chlorpyrifos is an organophosphorus insecticide widely used in Chilean agriculture in the control of plagues of insects in soil and several crops. From an environmental point of view, to know the behavior and fate of Chlorpyrifos under different moisture regimes in soil is important because it contributes to optimize its use, assuring that collateral effects do not take place inside or outside the application area and in addition it specifies the optimal conditions of application to obtain better results in the treatment with the land insecticide. In this work it was studied the half life of Chlorpyrifos ( 14 C) in an agricultural soil of VI Region, by means of the use of Isotopic techniques, under two moisture regimes of 50 and 75% of the Field Capacity. The ground samples were fortified with doses of 10 mg/Kg and incubated to 20 o C and in absence of light. The dissipation of Chlorpyrifos in soil was determined during 110 days of test, through the quantification of remaining 14 CO 2 by liquid scintillation counting. Results show temporary differences in the half life for different moisture regimes, with T 1/2 of 21 and 28 days for the soil to 75 and 50% of the Field Capacity, respectively. It was studied the factors related to soil and plaguicide that could affect speed of degradation, either accelerating or inhibiting the process of dissipation of Chlorpyrifos, under the described moisture regimes. The results indicated that the fast degradation of the insecticide organophosphorus in the soil to 75% of the CC is product of biotic and abiotic processes. Between the abiotic processes the neutral hydrolysis constituted the principal route of dissipation, mainly due to the moisture content and pH presented in soil (pH 7,2). Nevertheless, factors as the high content of organic matter of the soil, low water solubility, high coefficient of adsorption and bond p=S of the Chlorpyrifos, they suggest the sorption process would inhibit hydrolysis, slowing down the

  16. NK cell-like behavior of Valpha14i NK T cells during MCMV infection.

    Directory of Open Access Journals (Sweden)

    Johnna D Wesley

    2008-07-01

    Full Text Available Immunity to the murine cytomegalovirus (MCMV is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Valpha14 invariant natural killer T cell response to MCMV has not been examined. We found that Valpha14i NK T cells become activated and produce significant levels of IFN-gamma, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Valpha14i NK T cells into MCMV-infected CD1d(-/- mice demonstrate that CD1d is dispensable for Valpha14i NK T cell activation. In contrast, both IFN-alpha/beta and IL-12 are required for optimal activation. Valpha14i NK T cell-derived IFN-gamma is partially dependent on IFN-alpha/beta but highly dependent on IL-12. Valpha14i NK T cells contribute to the immune response to MCMV and amplify NK cell-derived IFN-gamma. Importantly, mortality is increased in CD1d(-/- mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Valpha14i NK T cells that act as effector T cells during bacterial infection, but have NK cell-like behavior during the innate immune response to MCMV infection.

  17. HIV-1 isolation from infected peripheral blood mononuclear cells.

    Science.gov (United States)

    Dispinseri, Stefania; Saba, Elisa; Vicenzi, Elisa; Kootstra, Neeltje A; Schuitemaker, Hanneke; Scarlatti, Gabriella

    2014-01-01

    Human immunodeficiency virus 1 (HIV-1) isolation from peripheral blood mononuclear cells (PBMCs) allows retrieval of replication-competent viral variants. In order to impose the smallest possible selective pressure on the viral isolates, isolation must be carried out in primary cultures of cells and not in tumor derived cell lines. The procedure involves culture of PBMCs from an infected patient with phytohemagglutinin (PHA)-stimulated PBMC from seronegative donors, which provide susceptible target cells for HIV replication. HIV can be isolated from the bulk population of PBMCs or after cloning of the cells to obtain viral biological clones. Viral production is determined with p24 antigen (Ag) detection assays or with reverse transcriptase (RT) activity assay. Once isolated, HIV-1 can be propagated by infecting PHA-stimulated PBMCs from healthy donors. Aliquots from culture with a high production of virus are stored for later use.

  18. Research progress of follicular cytotoxic T cells in HIV infection

    Directory of Open Access Journals (Sweden)

    Guo Ming

    2018-04-01

    Full Text Available Recently, a new type of CD8+ T-cell subset, namely, the chemokine (C-X-C motif receptor 5 (CXCR5+ cluster of differentiation (CD8+ T-cell subset (also called the follicular cytotoxic T-cell (TFC subgroup, has been discovered around B-cell follicles. The discovery has aroused widespread interest. However, the processes and mechanisms of TFCs taking part in the immune response of the germinal center and their specific roles must still be clearly identified. This article reviews domestic and foreign studies on factors regulating the phenotype, physiological functions, maturity, and differentiation of TFCs and roles and clinical significance of these cells in HIV infection. This review has shown good application prospects for TFCs. The author believes that further studies on TFCs can provide another tool for cytotherapy to control or cure chronic viral infections or tumors.

  19. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    -lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. Conclusion Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.

  20. Secretin receptor involvement in prion-infected cells and animals.

    Science.gov (United States)

    Kimura, Tomohiro; Nishizawa, Keiko; Oguma, Ayumi; Nishimura, Yuki; Sakasegawa, Yuji; Teruya, Kenta; Nishijima, Ichiko; Doh-ura, Katsumi

    2015-07-08

    The cellular mechanisms behind prion biosynthesis and metabolism remain unclear. Here we show that secretin signaling via the secretin receptor regulates abnormal prion protein formation in prion-infected cells. Animal studies demonstrate that secretin receptor deficiency slightly, but significantly, prolongs incubation time in female but not male mice. This gender-specificity is consistent with our finding that prion-infected cells are derived from females. Therefore, our results provide initial insights into the reasons why age of disease onset in certain prion diseases is reported to occur slightly earlier in females than males. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Susceptibility of Primary Human Choroid Plexus Epithelial Cells and Meningeal Cells to Infection by JC Virus.

    Science.gov (United States)

    O'Hara, Bethany A; Gee, Gretchen V; Atwood, Walter J; Haley, Sheila A

    2018-04-15

    JC polyomavirus (JCPyV) establishes a lifelong persistence in roughly half the human population worldwide. The cells and tissues that harbor persistent virus in vivo are not known, but renal tubules and other urogenital epithelial cells are likely candidates as virus is shed in the urine of healthy individuals. In an immunosuppressed host, JCPyV can become reactivated and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system. Recent observations indicate that JCPyV may productively interact with cells in the choroid plexus and leptomeninges. To further study JCPyV infection in these cells, primary human choroid plexus epithelial cells and meningeal cells were challenged with virus, and their susceptibility to infection was compared to the human glial cell line, SVG-A. We found that JCPyV productively infects both choroid plexus epithelial cells and meningeal cells in vitro Competition with the soluble receptor fragment LSTc reduced virus infection in these cells. Treatment of cells with neuraminidase also inhibited both viral infection and binding. Treatment with the serotonin receptor antagonist, ritanserin, reduced infection in SVG-A and meningeal cells. We also compared the ability of wild-type and sialic acid-binding mutant pseudoviruses to transduce these cells. Wild-type pseudovirus readily transduced all three cell types, but pseudoviruses harboring mutations in the sialic acid-binding pocket of the virus failed to transduce the cells. These data establish a novel role for choroid plexus and meninges in harboring virus that likely contributes not only to meningoencephalopathies but also to PML. IMPORTANCE JCPyV infects greater than half the human population worldwide and causes central nervous system disease in patients with weakened immune systems. Several recent reports have found JCPyV in the choroid plexus and leptomeninges of patients with encephalitis. Due to their role in forming the blood

  2. Precision measurement of the half-life and branching ratio of the T=1/2 mirror $\\beta$-decay of $^{37}$K

    CERN Multimedia

    We propose to study the T=1/2 mirror $\\beta$-decay of $^{37}$K. Nuclear mirror $\\beta$-decay is a competitive means to test the electroweak model by means of the high-precision measurement of V$_{ud}$ element of the CKM quark mixing matrix. One key ingredient to obtain V$_{ud}$ is the force of the transition, Ft, which has to be determined with a relative precision below 10$^{−3}$. This quantity is related to the half-life T$_{1/2}$ of the decaying nucleus, the branching ratio BR for this decay and the mass difference between the mother and daughter nucleus (Q value). Another important feature is the mixing ratio $\\rho$ between the Fermi and the Gamow-Teller character of the transition. In most cases, $\\rho$ is the major contributor to the uncertainty on Ft. Available data concerning T$_{1/2}$ and BR of $^{37}$K suffer from a lack of precision that will be easily reduced by a dedicated experiment.

  3. New limit for the half-life of double beta decay of {sup 94}Zr to the first excited state of {sup 94}Mo

    Energy Technology Data Exchange (ETDEWEB)

    Dokania, N.; Nanal, V.; Gupta, G.; Pillay, R.G.; Ghosh, C. [Tata Institute of Fundamental Research, Department of Nuclear and Atomic Physics, Mumbai (India); Pal, S. [Tata Institute of Fundamental Research, Pelletron Linac Facility, Mumbai (India); Rath, P.K. [University of Lucknow, Department of Physics, Lucknow (India); Tretyak, V.I. [Institute for Nuclear Research, Kyiv (Ukraine); Garai, A.; Krishnamoorthy, H. [Tata Institute of Fundamental Research, India-based Neutrino Observatory, Mumbai (India); Homi Bhabha National Institute, Mumbai (India); Raina, P.K. [Indian Institute of Technology, Department of Physics, Rupnagar (India); Bhushan, K.G. [Bhabha Atomic Research Centre, Technical Physics Division, Mumbai (India)

    2017-04-15

    Neutrinoless double beta decay is a phenomenon of fundamental interest in particle physics. The decay rates of double beta decay transitions to the excited states can provide input for Nuclear Transition Matrix Element calculations for the relevant two neutrino double beta decay process. It can be useful as supplementary information for the calculation of Nuclear Transition Matrix Element for the neutrinoless double beta decay process. In the present work, double beta decay of {sup 94}Zr to the 2{sup +}{sub 1} excited state of {sup 94}Mo at 871.1 keV is studied using a low background ∝ 230 cm{sup 3} HPGe detector. No evidence of this decay was found with a 232 g.y exposure of natural zirconium. The lower half-life limit obtained for the double beta decay of {sup 94}Zr to the 2{sup +}{sub 1} excited state of {sup 94}Mo is T{sub 1/2}(0ν + 2ν) > 3.4 x 10{sup 19} y at 90% C.L., an improvement by a factor of ∝ 4 over the existing experimental limit at 90% C.L. The sensitivity is estimated to be T{sub 1/2} (0ν + 2ν) > 2.0 x 10{sup 19} y at 90% C.L. using the Feldman-Cousins method. (orig.)

  4. Precision measurement of the half-life and the $\\beta$-decay Q value of the superallowed 0$^{+}\\rightarrow$ 0$^{+}\\beta$-decay of $^{38}$Ca

    CERN Multimedia

    2002-01-01

    We propose to study the $\\beta$-decay of $^{38}$Ca. In a first instance, we intend to perform a high-precision study of the half-life of this nucleus as well as a measurement of its $\\beta$-decay Q-value with ISOLTRAP. At a later stage, we propose to study its decay branches to determine the super-allowed branching ratio with high precision. These measurements are essential to improve our understanding of the theoretical corrections (in particular the $\\delta$c correction factor) needed to calculate the universal Ft value from the ft value determined for individual nuclei. For this nucleus, the correction factor is predicted to increase significantly as compared to the nine well-studied nuclei between $^{10}$C and $^{54}$Co and the model calculations used to determine the corrections, in particular the shell-model calculations, are well under control in this mass region. Therefore, the T$_{Z}$= -1 nuclei between A=18 and A=38 are ideal test cases for the correction factors which limit today the precision on t...

  5. Effective half-life of sup 131 I during treatment of autonomous thyroid disease. Untersuchungen zur effektiven Halbwertszeit des sup 131 J bei der Radiojodbehandlung der Schilddruesenautonomie

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, B.; Bares, R.; Buell, U. (Technische Hochschule Aachen (Germany, F.R.). Klinik fuer Nuklearmedizin)

    1991-06-01

    In order to compute effective half-life of {sup 131}I after application of therapeutic doses (T{sub eff}), the time course of whole-body radioactivity was evaluated retrospectively in 115 patients with benign thyroid diseases (multinodular autonomous adenoma, solitary autonomous adenoma or Graves' disease). Because of a large overlap of T{sub eff} in the various diseases analyzed, courses of all patients who did (group Ts, 24 cases) or did not (group kTs, 91 cases) receive antithyroid drugs during therapy were summarized. In group Ts a mean T{sub eff} of 5.0+-0.9 d was found which was significantly (p<0.01) lower than the mean T{sub eff} of 6.3+-0.9 d in group kTs. We believe that the mean T{sub eff} is a practical alternative in radioiodine dosimetry if an exact determination of T{sub eff} cannot be performed because of shortage of time. (orig.).

  6. Fusion to Human Serum Albumin Extends the Circulatory Half-Life and Duration of Antithrombotic Action of the Kunitz Protease Inhibitor Domain of Protease Nexin 2.

    Science.gov (United States)

    Sheffield, William P; Eltringham-Smith, Louise J; Bhakta, Varsha

    2018-01-01

    The Kunitz Protease Inhibitor (KPI) domain of protease nexin 2 (PN2) potently inhibits coagulation factor XIa. Recombinant KPI has been shown to inhibit thrombosis in mouse models, but its clearance from the murine circulation remains uncharacterized. The present study explored the pharmacokinetic and pharmacodynamic effects of fusing KPI to human serum albumin (HSA) in fusion protein KPIHSA. Hexahistidine-tagged KPI (63 amino acids) and KPIHSA (656 amino acids) were expressed in Pichia pastoris yeast and purified by nickel-chelate chromatography. Clearance profiles in mice were determined, as well as the effects of KPI or KPIHSA administration on FeCl3-induced vena cava thrombus size or carotid artery time to occlusion, respectively. Fusion to HSA increased the mean terminal half-life of KPI by 8-fold and eliminated its interaction with the low density lipoprotein receptor-related protein. KPI and KPIHSA similarly reduced thrombus size and occlusion in both venous and arterial thrombosis models when administered at the time of injury, but only KPI was effective when administered one hour before injury. Albumin fusion deflects KPI from rapid in vivo clearance without impairing its antithrombotic properties and widens its potential therapeutic window. © 2018 The Author(s). Published by S. Karger AG, Basel.

  7. Modulation of antigen presenting cell functions during chronic HPV infection

    Directory of Open Access Journals (Sweden)

    Abate Assefa Bashaw

    2017-12-01

    Full Text Available High-risk human papillomaviruses (HR-HPV infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells. However, HR-HPV have adopted various immunosuppressive strategies, with modulation of DC function crucial to escape from the host adaptive immune response. HPV E6 and E7 oncoproteins alter recruitment and localization of epidermal DCs, while soluble regulatory factors derived from HPV-induced hyperplastic epithelium change DC development and influence initiation of specific cellular immune responses. This review focuses on current evidence for HR-HPV manipulation of antigen presentation in dendritic cells and escape from host immunity.

  8. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  9. Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2017-03-01

    Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  10. Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection

    NARCIS (Netherlands)

    Geldmacher, Christof; Ngwenyama, Njabulo; Schuetz, Alexandra; Petrovas, Constantinos; Reither, Klaus; Heeregrave, Edwin J.; Casazza, Joseph P.; Ambrozak, David R.; Louder, Mark; Ampofo, William; Pollakis, Georgios; Hill, Brenna; Sanga, Erica; Saathoff, Elmar; Maboko, Leonard; Roederer, Mario; Paxton, William A.; Hoelscher, Michael; Koup, Richard A.

    2010-01-01

    HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common

  11. Helicobacter pylori impairs murine dendritic cell responses to infection.

    Directory of Open Access Journals (Sweden)

    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  12. DRAM Triggers Lysosomal Membrane Permeabilization and Cell Death in CD4+ T Cells Infected with HIV

    Science.gov (United States)

    Laforge, Mireille; Limou, Sophie; Harper, Francis; Casartelli, Nicoletta; Rodrigues, Vasco; Silvestre, Ricardo; Haloui, Houda; Zagury, Jean-Francois; Senik, Anna; Estaquier, Jerome

    2013-01-01

    Productive HIV infection of CD4+ T cells leads to a caspase-independent cell death pathway associated with lysosomal membrane permeabilization (LMP) and cathepsin release, resulting in mitochondrial outer membrane permeabilization (MOMP). Herein, we demonstrate that HIV infection induces damage-regulated autophagy modulator (DRAM) expression in a p53-dependent manner. Knocking down the expression of DRAM and p53 genes with specific siRNAs inhibited autophagy and LMP. However, inhibition of Atg5 and Beclin genes that prevents autophagy had a minor effect on LMP and cell death. The knock down of DRAM gene inhibited cytochrome C release, MOMP and cell death. However, knocking down DRAM, we increased viral infection and production. Our study shows for the first time the involvement of DRAM in host-pathogen interactions, which may represent a mechanism of defense via the elimination of infected cells. PMID:23658518

  13. DRAM triggers lysosomal membrane permeabilization and cell death in CD4(+ T cells infected with HIV.

    Directory of Open Access Journals (Sweden)

    Mireille Laforge

    Full Text Available Productive HIV infection of CD4(+ T cells leads to a caspase-independent cell death pathway associated with lysosomal membrane permeabilization (LMP and cathepsin release, resulting in mitochondrial outer membrane permeabilization (MOMP. Herein, we demonstrate that HIV infection induces damage-regulated autophagy modulator (DRAM expression in a p53-dependent manner. Knocking down the expression of DRAM and p53 genes with specific siRNAs inhibited autophagy and LMP. However, inhibition of Atg5 and Beclin genes that prevents autophagy had a minor effect on LMP and cell death. The knock down of DRAM gene inhibited cytochrome C release, MOMP and cell death. However, knocking down DRAM, we increased viral infection and production. Our study shows for the first time the involvement of DRAM in host-pathogen interactions, which may represent a mechanism of defense via the elimination of infected cells.

  14. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    María Laura Chiribao

    2014-01-01

    Full Text Available Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response, a great number of transcription factors (including the majority of NFκB family members, and host metabolism (cholesterol, fatty acids, and phospholipids. These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination.

  15. Transfusion Related Hepatitis C Virus (HCV) Infection in Sickle Cell ...

    African Journals Online (AJOL)

    Rev Olaleye

    ABSTRACT: This study aimed to determine retrospectively, the prevalence of hepatitis C virus infection in relation to a background history of blood transfusion; through anti HCV antibody screening test, amongst adult sickle cell disease patients. Anti HCV antibody was tested for in the serum of 92 consecutively selected ...

  16. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  17. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  18. T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

    Science.gov (United States)

    Pallikkuth, Suresh; de Armas, Lesley; Rinaldi, Stefano; Pahwa, Savita

    2017-01-01

    T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

  19. Skewing to the LFA-3 adhesion pathway by influenza infection of antigen-presenting cells

    NARCIS (Netherlands)

    van Kemenade, F. J.; Kuijpers, K. C.; de Waal-Malefijt, R.; van Lier, R. A.; Miedema, F.

    1993-01-01

    The effect of influenza (FLU) infection on heterotypic conjugate formation between antigen-presenting cells and T lymphocytes has been studied with FLU-specific T cell clones and FLU-infected B-lymphoblastoid cells (B-LCL). Conjugate formation between FLU-infected B-LCL (FLU+ B-LCL) and T cells was

  20. Brefeldin A inhibits pestivirus release from infected cells, without affecting its assembly and infectivity

    International Nuclear Information System (INIS)

    Macovei, Alina; Zitzmann, Nicole; Lazar, Catalin; Dwek, Raymond A.; Branza-Nichita, Norica

    2006-01-01

    The enveloped bovine viral diarrhea virus (BVDV) is a member of the Pestivirus genus within the Flaviviridae family. While considerable information has been gathered on virus entry into the host cell, genome structure and protein function, little is known about pestivirus morphogenesis and release from cells. Here, we analyzed the intracellular localization, N-glycan processing and secretion of BVDV using brefeldin A (BFA), which blocks protein export from the endoplasmic reticulum (ER) and causes disruption of the Golgi complex with subsequent fusion of its cis and medial cisternae with the ER. BFA treatment of infected cells resulted in complete inhibition of BVDV secretion and increased co-localization of the envelope glycoproteins with the cis-Golgi marker GM 130. Processing of the N-linked glycans was affected by BFA, however, virus assembly was not perturbed and intracellular virions were fully infectious, suggesting that trafficking beyond the cis-Golgi is not a prerequisite for pestivirus infectivity

  1. Brefeldin A inhibits pestivirus release from infected cells, without affecting its assembly and infectivity.

    Science.gov (United States)

    Macovei, Alina; Zitzmann, Nicole; Lazar, Catalin; Dwek, Raymond A; Branza-Nichita, Norica

    2006-08-04

    The enveloped bovine viral diarrhea virus (BVDV) is a member of the Pestivirus genus within the Flaviviridae family. While considerable information has been gathered on virus entry into the host cell, genome structure and protein function, little is known about pestivirus morphogenesis and release from cells. Here, we analyzed the intracellular localization, N-glycan processing and secretion of BVDV using brefeldin A (BFA), which blocks protein export from the endoplasmic reticulum (ER) and causes disruption of the Golgi complex with subsequent fusion of its cis and medial cisternae with the ER. BFA treatment of infected cells resulted in complete inhibition of BVDV secretion and increased co-localization of the envelope glycoproteins with the cis-Golgi marker GM 130. Processing of the N-linked glycans was affected by BFA, however, virus assembly was not perturbed and intracellular virions were fully infectious, suggesting that trafficking beyond the cis-Golgi is not a prerequisite for pestivirus infectivity.

  2. Brucella abortus Cell Cycle and Infection Are Coordinated.

    Science.gov (United States)

    De Bolle, Xavier; Crosson, Sean; Matroule, Jean-Yves; Letesson, Jean-Jacques

    2015-12-01

    Brucellae are facultative intracellular pathogens. The recent development of methods and genetically engineered strains allowed the description of cell-cycle progression of Brucella abortus, including unipolar growth and the ordered initiation of chromosomal replication. B. abortus cell-cycle progression is coordinated with intracellular trafficking in the endosomal compartments. Bacteria are first blocked at the G1 stage, growth and chromosome replication being resumed shortly before reaching the intracellular proliferation compartment. The control mechanisms of cell cycle are similar to those reported for the bacterium Caulobacter crescentus, and they are crucial for survival in the host cell. The development of single-cell analyses could also be applied to other bacterial pathogens to investigate their cell-cycle progression during infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection.

    Directory of Open Access Journals (Sweden)

    Kristin L Boswell

    2014-01-01

    Full Text Available The interaction between follicular T helper cells (TFH and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination. Recent studies described a functional equivalent of these cells among circulating CD4 T cells, referred to as peripheral TFH cells. Here, we characterize the phenotype and in vitro B cell helper activity of peripheral TFH populations, as well as the effect of HIV infection on these populations. In co-culture experiments we confirmed CXCR5+ cells from HIV-uninfected donors provide help to B cells and more specifically, we identified a CCR7(highCXCR5(highCCR6(highPD-1(high CD4 T cell population that secretes IL-21 and enhances isotype-switched immunoglobulin production. This population is significantly decreased in treatment-naïve, HIV-infected individuals and can be recovered after anti-retroviral therapy. We found impaired immunoglobulin production in co-cultures from HIV-infected individuals and found no correlation between the frequency of peripheral TFH cells and memory B cells, or with neutralization activity in untreated HIV infection in our cohort. Furthermore, we found that within the peripheral TFH population, the expression level of TFH-associated genes more closely resembles a memory, non-TFH population, as opposed to a TFH population. Overall, our data identify a heterogeneous population of circulating CD4 T cells that provides in vitro help to B cells, and challenges the origin of these cells as memory TFH cells.

  4. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  5. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  6. Cell-cell transmission of VSV-G pseudotyped lentivector particles.

    Directory of Open Access Journals (Sweden)

    Amy M Skinner

    Full Text Available Many replicating viruses, including HIV-1 and HTLV-1, are efficiently transmitted from the cell surface of actively infected cells upon contact with bystander cells. In a previous study, we reported the prolonged cell surface retention of VSV-G replication-deficient pseudotyped lentivector prior to endocytic entry. However, the competing kinetics of cell surface versus dissociation, neutralization or direct transfer to other cells have received comparatively little attention. Here we demonstrate that the relative efficiency of cell-cell surface transmission can outpace "cell-free" transduction at limiting vector input. This coincides with the prolonged half-life of cell bound vector but occurs, unlike HTLV-1, without evidence for particle aggregation. These studies suggest that cell-surface attachment stabilizes particles and alters neutralization kinetics. Our experiments provide novel insight into the underexplored cell-cell transmission of pseudotyped particles.

  7. 6K2-induced vesicles can move cell to cell during turnip mosaic virus infection

    Directory of Open Access Journals (Sweden)

    Romain eGrangeon

    2013-12-01

    Full Text Available To successfully infect plants, viruses replicate in an initially infected cell and then move to neighboring cells through plasmodesmata (PDs. However, the nature of the viral entity that crosses over the cell barrier into non-infected ones is not clear. The membrane-associated 6K2 protein of turnip mosaic virus (TuMV induces the formation of vesicles involved in the replication and intracellular movement of viral RNA. This study shows that 6K2-induced vesicles trafficked towards the plasma membrane and were associated with plasmodesmata (PD. We demonstrated also that 6K2 moved cell-to-cell into adjoining cells when plants were infected with TuMV. 6K2 was then fused to photo-activable GFP (6K2:PAGFP to visualize how 6K2 move intercellularly during TuMV infection. After activation, 6K2:PAGFP-tagged vesicles moved to the cell periphery and across the cell wall into adjacent cells. These vesicles were shown to contain the viral RNA-dependent RNA polymerase and viral RNA. Symplasmic movement of TuMV may thus be achieved in the form of a membrane-associated viral RNA complex induced by 6K2.

  8. Infectious mononucleosis accompanied by clonal proliferation of EBV-infected cells and infection of CD8-positive cells.

    Science.gov (United States)

    Arai, Ayako; Yamaguchi, Takeshi; Komatsu, Honami; Imadome, Ken-Ichi; Kurata, Morito; Nagata, Kaoru; Miura, Osamu

    2014-01-01

    A 22-year-old male was admitted for a sustained fever of 2 months, lymphadenopathy, and liver dysfunction. Anti-VCA-IgM antibody was positive, with elevated Epstein-Barr virus (EBV)-DNA load in the peripheral blood. Liver biopsy revealed infiltration of CD8-positive and EBV-positive cells. Most peripheral blood mononuclear cells (PBMCs) were also positive for CD8, and showed detectable levels of EBV-DNA. Monoclonal proliferation of EBV-infected cells was detected in the PBMCs by Southern blotting for EBV-terminal repeat (EBV-TR). Although EBV-positive T-cell lymphoproliferative disease (EBV-T-LPD) was suspected, the symptoms spontaneously resolved within 12 months. Anti-VCA-IgM antibody and the clonal band of EBV-TR were negative 1 year after the onset, while anti-EBNA antibody was positive. The final diagnosis was thus confirmed as infectious mononucleosis (IM). Our results indicate that EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells may be temporally detected in IM. EBV-T-LPDs should be carefully excluded in such cases.

  9. Differential proteome analysis of chikungunya virus infection on host cells.

    Directory of Open Access Journals (Sweden)

    Christina Li-Ping Thio

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach. METHODOLOGY AND PRINCIPAL FINDINGS: The whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE. Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP and cell cycle regulation. CONCLUSION/SIGNIFICANCE: This study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1 regulation (in favour of virus survival, replication and transmission. While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

  10. Anti-restenotic effect of copper-62 liquid-filled balloon in porcine coronary arteries: novel use of a short half-life positron emitter

    International Nuclear Information System (INIS)

    Chan, Rosanna C.; Lacy, Jeffrey L.; Bhargava, Balram; Collins, Sara D.; Cates, Pamela; Cottin, Yves; Kollum, Marc; Yang, Nathan; Haynes, Neal G.; Martin, Christopher S.; Nayak, Nisha; Vodovotz, Yoram; Kim, Han-Soo; Waksman, Ron

    2000-01-01

    Purpose: To determine the efficacy of the use of copper-62, a positron emitter with a half-life of 9.7 minutes, as an intracoronary brachytherapy (IRBT) source in the prevention of neointima formation (NF) following overstretch balloon injury (BI) in the porcine model. Methods and Materials: Sixteen swine were treated after BI to their left anterior descending (LAD), left circumflex (LCX), and/or right coronary artery (RCA). Twelve of the injured arteries received placebo and 10 received 25 Gy, delivered to 0.5 mm from the surface of the treatment balloon filled with liquid 62 Cu. Dosimetry was based on Monte Carlo calculations. Two weeks after treatment, the animals were sacrificed, and the treated coronaries were perfusion-fixed and stained. Intimal area (IA) and medial fracture length (FL) were analyzed by computer-aided histomorphometry. Results: The ( 62 Zn/ 62 Cu) generator, together with a rapid concentration process, was successful in delivering the short-lived 62 Cu at the high concentration required for intravascular brachytherapy (IVBT). The fracture length in the two groups was similar (2.10 ± 0.57; 2.02 ± 0.77; p = NS). Arteries studied showed significant reduction in NF (IA: 0.23 ± 0.47 mm 2 vs. 1.08 ± 0.57 mm 2 ; p 62 Cu as an IVBT source is safe and feasible. All 16 swine tolerated the treatment well with no radiation-induced side effects or symptoms throughout the 2-week period. The isotope delivered the dose necessary to inhibit NF in the porcine coronary BI model

  11. Distribution of ascorbate-2-sulfate and distribution, half-life and turnover rates of [1-14C]ascorbic acid in rainbow trout

    International Nuclear Information System (INIS)

    Tucker, B.W.; Halver, J.E.

    1984-01-01

    Rainbow trout (250 g) were maintained at 15 degrees C for 3 months on a low ascorbic acid diet, given [1- 14 C]ascorbic acid by gavage, then fed the NAS/NRC requirement 12 times per week. Total urine, fecal water and branchial water were collected daily from five fish placed in metabolism chambers for four successive 5-day periods. Tissue samples were analyzed for 14 C, ascorbic acid (C1) and ascorbate-2-sulfate (C2). Excretion analysis indicated t1/2 . 42 days. After 20 days, the feeding schedule was changed to 3 times per week. Fish fed 14 C were sampled after 1, 2, 3 and 4 months. The half-life in each organ except brain was inversely proportional to the dietary level of ascorbate. Concentrations of C1 and C2 in the various tissues reflected dietary intake of vitamin C. Total C (CT . C1 + C2) levels were maintained in the liver even with the low vitamin C diet. Estimates of body pool for C1 are 27-29 mg/kg. At the higher ascorbate intake CT was 92-114 mg/kg, but decreased by 34% at the lower feeding rate to 51-62 mg/kg. Data indicate that there are two or more body pools that include a store of C2, which is readily interconverted in metabolizing tissues to and from C1. Since air and water stable C2 is antiscorbutic for fish, it is the preferred form of ascorbate for fish feeds

  12. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Science.gov (United States)

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

    2016-01-01

    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  13. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  14. Epithelial cells from smokers modify dendritic cell responses in the context of influenza infection

    Science.gov (United States)

    Epidemiologic evidence suggests that cigarette smoking is a risk factor for infection with influenza, but the mechanisms underlying this susceptibility remain unknown. To ascertain if airway epithelial cells from smokers demonstrate a decreased ability to orchestrate an influenza...

  15. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

    International Nuclear Information System (INIS)

    Bonifati, Serena; Daly, Michele B.; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A.; Shepard, Caitlin; Kennedy, Edward M.; Kim, Dong-Hyun; Schinazi, Raymond F.; Kim, Baek; Wu, Li

    2016-01-01

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G_1/G_0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  16. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Bonifati, Serena [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Daly, Michele B. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); St Gelais, Corine; Kim, Sun Hee [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States); Hollenbaugh, Joseph A.; Shepard, Caitlin [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kennedy, Edward M. [Department of Molecular Genetics and Microbiology, Duke University, Durham, NC (United States); Kim, Dong-Hyun [Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Schinazi, Raymond F. [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Kim, Baek, E-mail: baek.kim@emory.edu [Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA (United States); Department of Pharmacy, School of Pharmacy, Kyung-Hee University, Seoul (Korea, Republic of); Wu, Li, E-mail: wu.840@osu.edu [Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH (United States)

    2016-08-15

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G{sub 1}/G{sub 0} phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection.

  17. Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors.

    Directory of Open Access Journals (Sweden)

    Dmitriy Mazurov

    2010-02-01

    Full Text Available We have developed an efficient method to quantify cell-to-cell infection with single-cycle, replication dependent reporter vectors. This system was used to examine the mechanisms of infection with HTLV-1 and HIV-1 vectors in lymphocyte cell lines. Effector cells transfected with reporter vector, packaging vector, and Env expression plasmid produced virus-like particles that transduced reporter gene activity into cocultured target cells with zero background. Reporter gene expression was detected exclusively in target cells and required an Env-expression plasmid and a viral packaging vector, which provided essential structural and enzymatic proteins for virus replication. Cell-cell fusion did not contribute to infection, as reporter protein was rarely detected in syncytia. Coculture of transfected Jurkat T cells and target Raji/CD4 B cells enhanced HIV-1 infection two fold and HTLV-1 infection ten thousand fold in comparison with cell-free infection of Raji/CD4 cells. Agents that interfere with actin and tubulin polymerization strongly inhibited HTLV-1 and modestly decreased HIV-1 cell-to-cell infection, an indication that cytoskeletal remodeling was more important for HTLV-1 transmission. Time course studies showed that HTLV-1 transmission occurred very rapidly after cell mixing, whereas slower kinetics of HIV-1 coculture infection implies a different mechanism of infectious transmission. HTLV-1 Tax was demonstrated to play an important role in altering cell-cell interactions that enhance virus infection and replication. Interestingly, superantigen-induced synapses between Jurkat cells and Raji/CD4 cells did not enhance infection for either HTLV-1 or HIV-1. In general, the dependence on cell-to-cell infection was determined by the virus, the effector and target cell types, and by the nature of the cell-cell interaction.

  18. Bovine aortic endothelial cells are susceptible to Hantaan virus infection

    International Nuclear Information System (INIS)

    Bahr, U.; Muranyi, W.; Mueller, S.; Kehm, R.; Handermann, M.; Darai, G.; Zeier, M.

    2004-01-01

    Hantavirus serotype Hantaan (HTN) is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS, lethality up to 10%). The natural host of HTN is Apodemus agrarius. Recent studies have shown that domestic animals like cattle are sporadically seropositive for hantaviruses. In the present study, the susceptibility of bovine aortic endothelial cells (BAEC) expressing α V β 3 -integrin to a HTN infection was investigated. Viral nucleocapsid protein and genomic RNA segments were detected in infected BAEC by indirect immunofluorescence assay, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The results of this study strongly support our previous observation on Puumala virus (PUU) that has been propagated efficiently in BAEC. These findings open a new window to contemplate the ecology of hantavirus infection and transmission route from animal to man

  19. Reduction of prion infectivity in packed red blood cells

    International Nuclear Information System (INIS)

    Morales, Rodrigo; Buytaert-Hoefen, Kimberley A.; Gonzalez-Romero, Dennisse; Castilla, Joaquin; Hansen, Eric T.; Hlavinka, Dennis; Goodrich, Raymond P.; Soto, Claudio

    2008-01-01

    The link between a new variant form of Creutzfeldt-Jakob disease (vCJD) and the consumption of prion contaminated cattle meat as well as recent findings showing that vCJD can be transmitted by blood transfusion have raised public health concerns. Currently, a reliable test to identify prions in blood samples is not available. The purpose of this study was to evaluate the possibility to remove scrapie prion protein (PrP Sc ) and infectivity from red blood cell (RBC) suspensions by a simple washing procedure using a cell separation and washing device. The extent of prion removal was assessed by Western blot, PMCA and infectivity bioassays. Our results revealed a substantial removal of infectious prions (≥3 logs of infectivity) by all techniques used. These data suggest that a significant amount of infectivity present in RBC preparations can be removed by a simple washing procedure. This technology may lead to increased safety of blood products and reduce the risk of further propagation of prion diseases.

  20. Rhizomucor and Scedosporium Infection Post Hematopoietic Stem-Cell Transplant

    Directory of Open Access Journals (Sweden)

    Dânia Sofia Marques

    2011-01-01

    Full Text Available Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis, its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies.

  1. Study of radioactive nuclides of very short half-life produced by fast neutrons; Etude de corps radioactifs a vie tres breve produits par neutrons rapides

    Energy Technology Data Exchange (ETDEWEB)

    Monnand, E [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1965-07-01

    Several radionuclides, already known, with half-lives ranging from 5 10{sup -5} to 1 second were observed by pulsed irradiations of C - Mg - Al - Y - In - Tl - Pb - Bi with 14.3 MeV neutrons. These radionuclides are: {sup 12}B (20 {+-} 0.4 ms) - {sup 24m}Na (20 {+-} 0.6 ms) - {sup 88m1}Y (0.332 {+-} 0.012 ms) - {sup 88m2}Y (14.6 {+-} 0.4 ms) - {sup 114m}In (43.5 {+-} 2 ms) - {sup 202m}Tl (0.570 {+-} 0.010 ms) - {sup 204m}Tl (0.063 {+-} 0.002 ms) - {sup 205m}Pb (5.5 {+-}0.3 ms) - {sup 206m}Pb (0.126 {+-} 0.006 ms) - {sup 207m}Pb (830 {+-} 30 ms) - {sup 208m}Bi (2.56 {+-} 0.1 ms). Their half-life, the {beta} and {gamma} rays energies and the production cross sections were measured. (author) [French] Plusieurs radionucleides deja connus, de periode comprise entre 5 10{sup -5} et 1 seconde ont ete observes par irradiation pulsee avec des neutrons de 14,3 MeV, des elements suivants: C - Mg - Al - Y - In - Tl - Pb - Bi. Ces radionucleides sont: {sup 12}B (20 {+-} 0.4 ms) - {sup 24m}Na (20 {+-} 0.6 ms) - {sup 88m1}Y (0.332 {+-} 0.012 ms) - {sup 88m2}Y (14.6 {+-} 0.4 ms) - {sup 114m}In (43.5 {+-} 2 ms) - {sup 202m}Tl (0.570 {+-} 0.010 ms) - {sup 204m}Tl (0.063 {+-} 0.002 ms) - {sup 205m}Pb (5.5 {+-}0.3 ms) - {sup 206m}Pb (0.126 {+-} 0.006 ms) - {sup 207m}Pb (830 {+-} 30 ms) - {sup 208m}Bi (2.56 {+-} 0.1 ms). Leur periode, l'energie des rayonnements {beta} et {gamma} emis, et la section efficace de production ont ete mesurees. (auteur)

  2. Prediction of clearance, volume of distribution and half-life by allometric scaling and by use of plasma concentrations predicted from pharmacokinetic constants: a comparative study.

    Science.gov (United States)

    Mahmood, I

    1999-08-01

    Pharmacokinetic parameters (clearance, CL, volume of distribution in the central compartment, VdC, and elimination half-life, t1/2beta) predicted by an empirical allometric approach have been compared with parameters predicted from plasma concentrations calculated by use of the pharmacokinetic constants A, B, alpha and beta, where A and B are the intercepts on the Y axis of the plot of plasma concentration against time and alpha and beta are the rate constants, both pairs of constants being for the distribution and elimination phases, respectively. The pharmacokinetic parameters of cefpiramide, actisomide, troglitazone, procaterol, moxalactam and ciprofloxacin were scaled from animal data obtained from the literature. Three methods were used to generate plots for the prediction of clearance in man: dependence of clearance on body weight (simple allometric equation); dependence of the product of clearance and maximum life-span potential (MLP) on body weight; and dependence of the product of clearance and brain weight on body weight. Plasma concentrations of the drugs were predicted in man by use of A, B, alpha and beta obtained from animal data. The predicted plasma concentrations were then used to calculate CL, VdC and t1/2beta. The pharmacokinetic parameters predicted by use of both approaches were compared with measured values. The results indicate that simple allometry did not predict clearance satisfactorily for actisomide, troglitazone, procaterol and ciprofloxacin. Use of MLP or the product of clearance and brain weight improved the prediction of clearance for these four drugs. Except for troglitazone, VdC and t1/2beta predicted for man by use of the allometric approach were comparable with measured values for the drugs studied. CL, VdC and t1/2beta predicted by use of pharmacokinetic constants were comparable with values predicted by simple allometry. Thus, if simple allometry failed to predict clearance of a drug, so did the pharmacokinetic constant

  3. Characterization of the liquid argon veto of the GERDA experiment and its application for the measurement of the "7"6Ge half-life

    International Nuclear Information System (INIS)

    Wegmann, Anne Christin

    2017-01-01

    The search for neutrinoless double-beta decay (0νββ) is one of the most active fields in modern particle physics as the observation of this process would prove lepton number violation and imply new physics beyond the Standard Model of particle physics. The GERDA experiment searches for this decay by operating bare Germanium detectors, enriched in the ββ isotope "7"6Ge, in liquid argon. For the first time, a ββ-experiment combines the excellent properties of semiconductor Germanium detectors with an active background suppression technique based on the simultaneous detection of liquid argon scintillation light by photomultiplier tubes and silicon photomultipliers coupled to scintillating fibers (LAr veto). The LAr veto has been successfully operated during the first six months of Phase II of the experiment and yielded - in combination with a Germanium detector pulse shape discrimination technique - a background index of (0.7"+"1"."1_-_0_._5).10"-"3 ((cts)/(kg.keV.yr)). With an ultimate exposure of 100 kg.yr this will allow for a 0νββ-decay half-life sensitivity of the Gerda Phase II experiment of 10"2"6 yr. Double-beta decay under the emission of two neutrinos (2νββ) is a second-order process but which is allowed by the Standard Model. The excellent background reduction of the LAr veto results in an unprecedented signal-to-background ratio of 30:1 in the energy region dominated by 2νββ-decay of "7"6Ge. The remaining background after LAr veto is estimated using the suppression factor from calibration source measurements and results in a measurement of T"2"ν_1_/_2=(1.98±0.02(stat)±0.05(syst)).10"2"1 yr and T_1_/_2"2"ν=(1.92 ±0.02(stat)±0.11(syst)).10"2"1 yr based on two different detector designs and give uncertainties on the detector parameters but both with improved systematic uncertainties in comparison to earlier measurements.

  4. Characterization of the liquid argon veto of the GERDA experiment and its application for the measurement of the {sup 76}Ge half-life

    Energy Technology Data Exchange (ETDEWEB)

    Wegmann, Anne Christin

    2017-01-18

    The search for neutrinoless double-beta decay (0νββ) is one of the most active fields in modern particle physics as the observation of this process would prove lepton number violation and imply new physics beyond the Standard Model of particle physics. The GERDA experiment searches for this decay by operating bare Germanium detectors, enriched in the ββ isotope {sup 76}Ge, in liquid argon. For the first time, a ββ-experiment combines the excellent properties of semiconductor Germanium detectors with an active background suppression technique based on the simultaneous detection of liquid argon scintillation light by photomultiplier tubes and silicon photomultipliers coupled to scintillating fibers (LAr veto). The LAr veto has been successfully operated during the first six months of Phase II of the experiment and yielded - in combination with a Germanium detector pulse shape discrimination technique - a background index of (0.7{sup +1.1}{sub -0.5}).10{sup -3} ((cts)/(kg.keV.yr)). With an ultimate exposure of 100 kg.yr this will allow for a 0νββ-decay half-life sensitivity of the Gerda Phase II experiment of 10{sup 26} yr. Double-beta decay under the emission of two neutrinos (2νββ) is a second-order process but which is allowed by the Standard Model. The excellent background reduction of the LAr veto results in an unprecedented signal-to-background ratio of 30:1 in the energy region dominated by 2νββ-decay of {sup 76}Ge. The remaining background after LAr veto is estimated using the suppression factor from calibration source measurements and results in a measurement of T{sup 2ν}{sub 1/2}=(1.98±0.02(stat)±0.05(syst)).10{sup 21} yr and T{sub 1/2}{sup 2ν}=(1.92 ±0.02(stat)±0.11(syst)).10{sup 21} yr based on two different detector designs and give uncertainties on the detector parameters but both with improved systematic uncertainties in comparison to earlier measurements.

  5. Pulse shape analysis for the GERDA experiment to set a new limit on the half-life of 0νββ decay of {sup 76}Ge

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Victoria Elisabeth

    2017-01-25

    The GERDA experiment searches for neutrinoless double beta (0νββ) decay of {sup 76}Ge using high purity germanium (HPGe) detectors operated in liquid argon (LAr). The aim is to explore half-lives of the order of 10{sup 26} yr. Therefore, GERDA relies on improved active background reduction techniques such as pulse shape discrimination (PSD) in which the time structure of the germanium signals is analyzed to discriminate signal- from background-like events. Two types of HPGe detectors are operated: semi-coaxial detectors previously used in the Heidelberg-Moscow and IGEX experiments and new Broad Energy Germanium (BEGe) detectors which feature an improved energy resolution and enhanced PSD. In Phase I of the experiment, five enriched BEGe detectors were used for the first time in the search for 0νββ decay. A PSD based on a single parameter, the ratio of the maximum current amplitude over the energy A/E is applied. 83% of the background events in a 232 keV region around Q{sub ββ} are rejected with a high signal efficiency of (92.1 ± 1.9) %. The achieved background index (BI) is (5.4{sup +4.1}{sub -3.4}) . 10{sup -3} (counts)/(keV.kg.yr). This is an improvement by a factor of 10 compared to previous germanium based 0νββ experiments. Phase II of the experiment includes a major upgrade: for further background rejection, the LAr cryostat is instrumented to detect argon scintillation light. Additional 25 BEGe detectors are installed. After PSD and LAr veto a BI of (0.7{sup +1.3}{sub -0.5}) . 10{sup -3} (counts)/(keV.kg.yr) is achieved. This is the best BI achieved in 0νββ experiments so far. A frequentist statistical analysis is performed on the combined data collected in GERDA Phase I and the first Phase II release. A new limit on the half-life of 0νββ decay of {sup 76}Ge is set to T{sup 0ν}{sub 1/2}>5.3.10{sup 25} yr at 90% C.L., with a median sensitivity of T{sup 0ν}{sub 1/2}>4.0.10{sup 25} yr at 90% C.L.

  6. Positive serum specific IgE has a short half-life in patients with penicillin allergy and reversal does not always indicate tolerance.

    Science.gov (United States)

    Hjortlund, Janni; Mortz, Charlotte Gotthard; Stage, Tore Bjerregaard; Skov, Per Stahl; Dahl, Ronald; Bindslev-Jensen, Carsten

    2014-01-01

    The positive and negative predictive values of specific IgE to penicillins are not well established for penicillin hypersensitivity. One reason may be that serum IgE levels to penicillin diminish over time. The objective in this study was to investigate variations in serum half-life (T½) for specific IgE to penicillins (s-IgE) and to evaluate the outcome of penicillin challenges in patients with previous but not present specific IgE to penicillins. Two subgroups were investigated. All included patients had a history of penicillin allergy with reported symptoms such as urticaria/angioedema or unclassified cutaneous rash. T½ of specific IgE to penicillins was calculated based on sera from 29 patients with repeated measurements of s-IgE. Twenty-two patients with a previous positive s-IgE was followed and challenged with penicillin when IgE had become negative. The T½ for s-IgE varied between the 26 patients with decreasing s-IgE from 1.6 months to 76.4 months and 52% had a T½ of less than a year. The three patients with stable and increasing IgE-values showed T½ approaching infinity A total of 29 challenges with β-lactams were performed. Four different patterns were seen when evaluating the clinical reaction to challenge (positive/negative) and post-challenge boost of s-IgE (yes/no). Eight (36.4%) had negative challenge and negative post-challenge s-IgE, eight (36.4%) negative challenge, but positive post-challenge s-IgE levels. 3 (13.6%) had positive challenge and positive post-challenge s-IgE whereas 3 (13.6%) were challenge positive, but had negative post-challenge s-IgE. Specific IgE to penicillins declines over time stressing the importance of a close time relation between diagnostic work-up and clinical reaction. Reversal of previously positive s-IgE may still be associated with positive penicillin challenges and/or re-boostering of s-IgE to positivity.

  7. Dendritic cell immunotherapy for HIV infection: from theory to reality.

    Science.gov (United States)

    Oshiro, Telma Miyuki; de Almeida, Alexandre; da Silva Duarte, Alberto José

    2009-11-01

    Knowledge concerning the immunology of dendritic cells (DCs) accumulated over the last few decades and the development of methodologies to generate and manipulate these cells in vitro has made their therapeutic application a reality. Currently, clinical protocols for DC-based therapeutic vaccine in HIV-infected individuals show that it is a safe and promising approach. Concomitantly, important advances continue to be made in the development of methodologies to optimize DC acquisition, as well as the selection of safe, immunogenic HIV antigens and the evaluation of immune response in treated individuals.

  8. Detection of bacteriophage-infected cells of Lactococcus lactis using flow cytometry

    DEFF Research Database (Denmark)

    Michelsen, Ole; Cuesta-Dominguez, Álvaro; Albrektsen, Bjarne

    2007-01-01

    Bacteriophage infection in dairy fermentation constitutes a serious problem worldwide. We have studied bacteriophage infection in Lactococcus lactis by using the flow cytometer. The first effect of the infection of the bacterium is a change from cells in chains toward single cells. We interpret...... describe a new method for detection of phage infection in Lactococcus lactis dairy cultures. The method is based on flow cytometric detection of cells with low-density cell walls. The method allows fast and early detection of phage-infected bacteria, independently of which phage has infected the culture...

  9. Microsporidia infection impacts the host cell's cycle and reduces host cell apoptosis

    Science.gov (United States)

    Higes, Mariano; Sagastume, Soledad; Juarranz, Ángeles; Dias-Almeida, Joyce; Budge, Giles E.; Meana, Aránzazu; Boonham, Neil

    2017-01-01

    Intracellular parasites can alter the cellular machinery of host cells to create a safe haven for their survival. In this regard, microsporidia are obligate intracellular fungal parasites with extremely reduced genomes and hence, they are strongly dependent on their host for energy and resources. To date, there are few studies into host cell manipulation by microsporidia, most of which have focused on morphological aspects. The microsporidia Nosema apis and Nosema ceranae are worldwide parasites of honey bees, infecting their ventricular epithelial cells. In this work, quantitative gene expression and histology were studied to investigate how these two parasites manipulate their host’s cells at the molecular level. Both these microsporidia provoke infection-induced regulation of genes involved in apoptosis and the cell cycle. The up-regulation of buffy (which encodes a pro-survival protein) and BIRC5 (belonging to the Inhibitor Apoptosis protein family) was observed after infection, shedding light on the pathways that these pathogens use to inhibit host cell apoptosis. Curiously, different routes related to cell cycle were modified after infection by each microsporidia. In the case of N. apis, cyclin B1, dacapo and E2F2 were up-regulated, whereas only cyclin E was up-regulated by N. ceranae, in both cases promoting the G1/S phase transition. This is the first report describing molecular pathways related to parasite-host interactions that are probably intended to ensure the parasite’s survival within the cell. PMID:28152065

  10. BACTERIAL INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    Elisa Balletto

    2015-07-01

    Full Text Available Bacterial infections are major complications after Hematopoietic Stem Cell Transplant (HSCT. They consist mainly of bloodstream infections (BSI, followed by pneumonia and gastrointestinal infections, including typhlitis and Clostridium difficile infection. Microbiological data come mostly from BSI. Coagulase negative staphylococci and Enterobacteriaceae are the most frequent pathogens causing approximately 25% of BSI each, followed by enterococci, P. aeruginosa and viridans streptococci. Bacterial pneumonia is frequent after HSCT, and Gram-negatives are predominant. Clostridium difficile infection affects approximately 15% of HSCT recipients, being more frequent in case of allogeneic than autologous HSCT. The epidemiology and the prevalence of resistant strains vary significantly between transplant centres. In some regions, multi-drug resistant Gram-negative rods are increasingly frequent. In others, vancomycin-resistant enterococci are predominant. In the era of an increasing resistance to antibiotics, the efficacy of fluoroquinolone prophylaxis and standard treatment of febrile neutropenia have been questioned. Therefore, thorough evaluation of local epidemiology is mandatory in order to decide the need for prophylaxis and the choice of the best regimen for empirical treatment of febrile neutropenia. For the latter, individualised approach has been proposed, consisting of either escalation or de-escalation strategy. De-escalation strategy is recommended is resistant bacteria should be covered upfront, mainly in patients with severe clinical presentation and previous infection or colonisation with a resistant pathogens. Non-pharmacological interventions, such as screening for resistant bacteria, applying isolation and contact precautions should be put in place in order to limit the spread of MDR bacteria. Antimicrobial stewardship program should be implemented in transplant centres.

  11. Direct measurement of the half-life of Rb{sup 87}; Mesure directe de la periode du rubidium-87; Pryamoe izmerenie poluraspada rubidiya-87; Medicion directa del periodo del {sup 87}Rb

    Energy Technology Data Exchange (ETDEWEB)

    McNair, A; Wilson, H W [United Kingdom Atomic Energy Authority, Aldermaston, Berks. (United Kingdom)

    1962-01-15

    The half-life of Rb{sup 87} has been measured directly by determining the specific activity by a counting method. The half-lives previously obtained lie in the range 4 - 6 x 10{sup 10} years, a value of 5 x 10{sup 10} years being taken usually. Direct counting is rather difficult because of the presence of a large number of very-low-energy electrons in the Rb{sup 87} spectrum. However, it is clearly very desirable to obtain a precise value by the counting method and this the authors have tried to do. In these measurements special attention must be paid to the reduction of thickness of source and of source backing. To increase the accuracy of the measurements, the following methods were used. The source thickness was reduced by use of (i) a 4-{pi} proportional counter of large source area (up to 100 cm{sup 2}), (ii) anti-coincidence operation to reduce background, and (iii) enriched Rb{sup 87} which permits a four-fold reduction in source thickness for a given activity. By these methods, sources down to 5 {mu}g/cm{sup 2} have been measured. Also the relationship between half-life and source thickness was examined so that correction could be made for the very small absorption which remained. The effect of source backing thickness is not so great and can be calculated from (i) the difference in count-rates on either side of the thin supports used and (ii) a study of dependence of half-life on source support thickness. These experiments give a value of about 5.25 x 10{sup 10} years for the half-life. (author) [French] On a mesure la periode du Tubidium-87 directement, en determinant l'activite specifique par comptage. Les periodes obtenues anterieurement se situent entre 4 et 6 {center_dot} 10{sup 10} ans; la valeur habituellement adoptee est de 5 {center_dot} 10{sup 10} ans. Le comptage direct est d'un emploi assez difficile par suite de la presence d'un grand nombre d'electrons de tres faible energie dans le spectre du rubidium-87. Il n'en serait pas moins tres utile

  12. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    Science.gov (United States)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  13. Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.

    Science.gov (United States)

    Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin

    2018-02-15

    Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel

  14. Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection.

    Science.gov (United States)

    Li, Haijun; Zhai, Naicui; Wang, Zhongfeng; Song, Hongxiao; Yang, Yang; Cui, An; Li, Tianyang; Wang, Guangyi; Niu, Junqi; Crispe, Ian Nicholas; Su, Lishan; Tu, Zhengkun

    2017-09-12

    HBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells. Monocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining. In chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation. Our findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Why infection-induced anorexia? The case for enhanced apoptosis of infected cells.

    Science.gov (United States)

    LeGrand, E K

    2000-04-01

    A medically important paradox is why the body's own cytokines lead to reduced appetite and apparently inefficient metabolism as part of the acute-phase response. This self-induced nutrient restriction occurs just when the body must maintain a fever and other defensive functions. This paradox is often ignored or considered a metabolic derangement. Others, recognizing it to be a programmed response which must have net beneficial effects, consider the nutrient restriction to be an attempt to deny resources to infectious organisms. However, this explanation fails to address how the pathogen can be harmed more than the host. The hypothesis presented here offers an explanation. Apoptosis, or cell suicide, is becoming recognized as a useful defense against intracellular parasites, and nutrient restriction promotes apoptosis. Thus, nutrient restriction may encourage apoptosis of infected cells. Nutrient restriction can thereby offer protection by simultaneously limiting nutrients to both the host cells and the infectious organisms. Copyright 2000 Harcourt Publishers Ltd.

  16. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

    International Nuclear Information System (INIS)

    Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

    1991-01-01

    We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

  17. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells.

    Science.gov (United States)

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-10-12

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24-36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection.

  18. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells

    Science.gov (United States)

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-01-01

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24–36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection. PMID:29022904

  19. Towards a better prediction of peak concentration, volume of distribution and half-life after oral drug administration in man, using allometry.

    Science.gov (United States)

    Sinha, Vikash K; Vaarties, Karin; De Buck, Stefan S; Fenu, Luca A; Nijsen, Marjoleen; Gilissen, Ron A H J; Sanderson, Wendy; Van Uytsel, Kelly; Hoeben, Eva; Van Peer, Achiel; Mackie, Claire E; Smit, Johan W

    2011-05-01

    It is imperative that new drugs demonstrate adequate pharmacokinetic properties, allowing an optimal safety margin and convenient dosing regimens in clinical practice, which then lead to better patient compliance. Such pharmacokinetic properties include suitable peak (maximum) plasma drug concentration (C(max)), area under the plasma concentration-time curve (AUC) and a suitable half-life (t(½)). The C(max) and t(½) following oral drug administration are functions of the oral clearance (CL/F) and apparent volume of distribution during the terminal phase by the oral route (V(z)/F), each of which may be predicted and combined to estimate C(max) and t(½). Allometric scaling is a widely used methodology in the pharmaceutical industry to predict human pharmacokinetic parameters such as clearance and volume of distribution. In our previous published work, we have evaluated the use of allometry for prediction of CL/F and AUC. In this paper we describe the evaluation of different allometric scaling approaches for the prediction of C(max), V(z)/F and t(½) after oral drug administration in man. Twenty-nine compounds developed at Janssen Research and Development (a division of Janssen Pharmaceutica NV), covering a wide range of physicochemical and pharmacokinetic properties, were selected. The C(max) following oral dosing of a compound was predicted using (i) simple allometry alone; (ii) simple allometry along with correction factors such as plasma protein binding (PPB), maximum life-span potential or brain weight (reverse rule of exponents, unbound C(max) approach); and (iii) an indirect approach using allometrically predicted CL/F and V(z)/F and absorption rate constant (k(a)). The k(a) was estimated from (i) in vivo pharmacokinetic experiments in preclinical species; and (ii) predicted effective permeability in man (P(eff)), using a Caco-2 permeability assay. The V(z)/F was predicted using allometric scaling with or without PPB correction. The t(½) was estimated from

  20. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  1. Gene expression in epithelial cells in response to pneumovirus infection

    Directory of Open Access Journals (Sweden)

    Rosenberg Helene F

    2001-05-01

    Full Text Available Abstract Respiratory syncytial virus (RSV and pneumonia virus of mice (PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

  2. Lysis of cells infected with typhus group rickettsiae by a human cytotoxic T cell clone

    International Nuclear Information System (INIS)

    Carl, M.; Robbins, F.; Hartzman, R.J.; Dasch, G.A.

    1987-01-01

    Cytolytic human T cells clones generated in response to the intracellular bacterium Rickettsia typhi were characterized. Growing clones were tested for their ability to proliferate specifically in response to antigens derived from typhus group rickettsiae or to lyse targets infected with R. typhi or Rickettsia prowazekii, as measured by 51 Cr-release from target cells. Two clones were able to lyse targets infected with typhus group rickettsiae. One of these clones was more fully characterized because of its rapid growth characteristics. This cytolytic clone was capable of lysing an autologous infected target as well as a target matched for class I and II histocompatibility leukocyte antigens (HLA). It was not capable, however, of lysing either a target mismatched for both class I and II HLA or a target partially matched for class I HLA. In addition, the clone exhibited specificity in that it was able to lyse an autologous target infected with typhus group rickettsiae, but did not lyse an autologous target infected with an antigenically distinct rickettsial species, Rickettsia tsutsugamushi. These results demonstrate, for the first time, that cells infected with intracellular bacteria can be lysed by human cytotoxic T lymphocytes

  3. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Ahsan, Muhammad H.; Gill, Amy F.; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

    2013-01-01

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

  4. Regulation of T cell migration during viral infection: role of adhesion molecules and chemokines

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, Anneline; Madsen, Andreas Nygaard

    2003-01-01

    T cell mediated immunity and in particular CD8+ T cells are pivotal for the control of most viral infections. T cells exclusively exert their antiviral effect through close cellular interaction with relevant virus-infected target cells in vivo. It is therefore imperative that efficient mechanisms...

  5. Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

    Science.gov (United States)

    Helmi, Nawal; Andrew, Peter W; Pandya, Hitesh C

    2015-05-15

    Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1β and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O₂-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells

    DEFF Research Database (Denmark)

    Fornara, O; Bartek, J; Rahbar, A

    2016-01-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express...... human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary...... GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co...

  7. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Directory of Open Access Journals (Sweden)

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  8. Dynamics of picornavirus RNA replication within infected cells

    DEFF Research Database (Denmark)

    Belsham, Graham; Normann, Preben

    2008-01-01

    Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks the initiat......Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks...... the initiation of negative-strand synthesis. We have now examined the dynamics of RNA replication, measured by quantitative RT-PCR, within cells infected with either swine vesicular disease virus (an enterovirus) or foot-and-mouth disease virus as regulated by the presence or absence of guanidine. Following...... the removal of guanidine from the infected cells, RNA replication occurs after a significant lag phase. This restoration of RNA synthesis requires de novo protein synthesis. Viral RNA can be maintained for at least 72 h within cells in the absence of apparent replication but guanidine-resistant virus can...

  9. Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

    Science.gov (United States)

    Hannemann, Sebastian; Galán, Jorge E

    2017-07-01

    Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

  10. Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.

    Directory of Open Access Journals (Sweden)

    Sebastian Hannemann

    2017-07-01

    Full Text Available Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.

  11. Cytotoxic CD4 T Cells: Differentiation, Function, and Application to Dengue Virus Infection.

    Science.gov (United States)

    Tian, Yuan; Sette, Alessandro; Weiskopf, Daniela

    2016-01-01

    Dengue virus (DENV) has spread through most tropical and subtropical areas of the world and represents a serious public health problem. The control of DENV infection has not yet been fully successful due to lack of effective therapeutics or vaccines. Nevertheless, a better understanding of the immune responses against DENV infection may reveal new strategies for eliciting and improving antiviral immunity. T cells provide protective immunity against various viral infections by generating effector cells that cooperate to eliminate antigens and memory cells that can survive for long periods with enhanced abilities to control recurring pathogens. Following activation, CD8 T cells can migrate to sites of infection and kill infected cells, whereas CD4 T cells contribute to the elimination of pathogens by trafficking to infected tissues and providing help to innate immune responses, B cells, as well as CD8 T cells. However, it is now evident that CD4 T cells can also perform cytotoxic functions and induce the apoptosis of target cells. Importantly, accumulating studies demonstrate that cytotoxic CD4 T cells develop following DENV infections and may play a crucial role in protecting the host from severe dengue disease. We review our current understanding of the differentiation and function of cytotoxic CD4 T cells, with a focus on DENV infection, and discuss the potential of harnessing these cells for the prevention and treatment of DENV infection and disease.

  12. A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time

    Directory of Open Access Journals (Sweden)

    Michael J. McFadden

    2018-02-01

    Full Text Available Zika virus (ZIKV is a re-emerging flavivirus that is transmitted to humans through the bite of an infected mosquito or through sexual contact with an infected partner. ZIKV infection during pregnancy has been associated with numerous fetal abnormalities, including prenatal lethality and microcephaly. However, until recent outbreaks in the Americas, ZIKV has been relatively understudied, and therefore the biology and pathogenesis of ZIKV infection remain incompletely understood. Better methods to study ZIKV infection in live cells could enhance our understanding of the biology of ZIKV and the mechanisms by which ZIKV contributes to fetal abnormalities. To this end, we developed a fluorescent cell-based reporter system allowing for live imaging of ZIKV-infected cells. This system utilizes the protease activity of the ZIKV non-structural proteins 2B and 3 (NS2B-NS3 to specifically mark virus-infected cells. Here, we demonstrate the utility of this fluorescent reporter for identifying cells infected by ZIKV strains of two lineages. Further, we use this system to determine that apoptosis is induced in cells directly infected with ZIKV in a cell-autonomous manner. Ultimately, approaches that can directly track ZIKV-infected cells at the single cell-level have the potential to yield new insights into the host-pathogen interactions that regulate ZIKV infection and pathogenesis.

  13. Altered T cell memory and effector cell development in chronic lymphatic filarial infection that is independent of persistent parasite antigen.

    Directory of Open Access Journals (Sweden)

    Cathy Steel

    2011-04-01

    Full Text Available Chronic lymphatic filarial (LF infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN, microfilaria (mf positive infected patients (Inf had a reduced CD4 central memory (T(CM compartment. In addition, Inf patients tended to have more effector memory cells (T(EM and fewer effector cells (T(EFF than did ENs giving significantly smaller T(EFF:T(EM ratios. These contracted T(CM and T(EFF populations were still evident in patients previously mf+ who had cleared their infection (CLInf. Moreover, the density of IL-7Rα, necessary for T memory cell maintenance (but decreased in T effector cells, was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-Rα, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children

  14. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status.

    Science.gov (United States)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  15. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract

    Science.gov (United States)

    The circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a H...

  16. Measles virus-specified polypeptides in infected cells

    International Nuclear Information System (INIS)

    Vainionpaepae, R.

    1979-01-01

    The synthesis of wild-type measles virus-specified polypeptides in Vero cells in pulse-chase experiments, in cells with synchronized protein synthesis by high salt concentration, and in the presence of proteolytic enzyme inhibitors was analyzed by polyacrylamide slab-gel electrophoresis. Six major (L, G, 2, NP, 5 and M) structural polypeptides were identified in infected cells. The results of pulse-chase experiments suggested that most of the structural polypeptides were synthesized at their final length. Polypeptide M was found to be sensitive to trypsin. In TLCK-treated cells its molecular weight was about 1000-2000 daltons higher than in untreated cells. A minor virus-specific polypeptide with a molecular weight of about 23,000 was found as a very faint and diffuse band. In addition, three nonstructural polypeptides with molecular weights of 65,000, 38,000 and 18,000 were also detected. The experiments with proteolytic enzyme inhibitors and with synchronized protein synthesis suggested that the polypeptide with a molecular weight of 65,000 might be a precursor of the structural polypeptide 5. (author)

  17. Preservative Monitoring of a Greek Woman with Hydrops Fetalis due to Parvovirus B19 Infection

    Directory of Open Access Journals (Sweden)

    Zacharias Fasoulakis

    2017-01-01

    Full Text Available Primate erythroparvovirus 1 (parvovirus B19 is a member of the Erythrovirus genus of the Parvoviridae family and it is one of the few members of the family known to be pathogenic in human. B19 infection is common and widespread with the virus being associated with numerous rheumatologic and haematologic manifestations. More specifically, maternal infection with parvovirus B19 during pregnancy can cause severe anemia which may lead to nonimmune hydrops or fetal demise, as a result of fetal erythroid progenitor cells infection with shortened half-life of erythrocytes. We present a rare case reported in the Greek population, of subclinical transient reticulocytopenia due to B19 parvovirus infection, in an asymptomatic pregnant woman, without medical history of hemoglobinopathy, and with the presence of hydrops fetalis during the third trimester of her pregnancy.

  18. Prosthetic graft infection: limitations of indium white blood cell scanning

    International Nuclear Information System (INIS)

    Brunner, M.C.; Mitchell, R.S.; Baldwin, J.C.; James, D.R.; Olcott, C. IV; Mehigan, J.T.; McDougall, I.R.; Miller, D.C.

    1986-01-01

    The lack of a rapid, noninvasive, and accurate method to confirm or rule out prosthetic graft infection continues to constitute a compelling and vexing clinical problem. A host of adjunctive diagnostic techniques has been used in the past, but early promising results subsequently have usually not yielded acceptable sensitivity (reflecting false negatives) and specificity (reflecting false positive) data. White blood cell (WBC) indium 111 scanning has recently been added to this list. The utility and accuracy of 111 In WBC scans were assessed by retrospective review of WBC scan results in 70 patients undergoing evaluation for possible prosthetic graft infection over a 7-year period. Operative and autopsy data (mean follow-up, 18 months for survivors with negative scans) were used to confirm the 22 positive, 45 negative, and three equivocal WBC scans. The false positive rate (+/- 70% confidence limits) was 36% +/- 6% (n = 8) among the 22 patients with positive scans (44% +/- 6% [11 of 25] if the three equivocal scans are included as false positive), yielding a specificity of 85% +/- 5% and an overall accuracy rate of 88% +/- 4% (80% +/- 5% and 84% +/- 5%, respectively, if the three equivocal cases are considered as false positive). All three patients with equivocal scans ultimately were judged not to have prosthetic graft infection. As implied by the high accuracy rate, the sensitivity of the test was absolute (100% [14 of 14]); there were no false negative results

  19. Laser irradiation reduces HIV-1 infection in TZM-bl cells

    CSIR Research Space (South Africa)

    Lugongolo, Masixole Y

    2016-10-01

    Full Text Available HIV-1 epidemic remains a major health challenge. This study explores the effects of low level laser therapy on HIV-1 infected cells. Infection is reduced by irradiation and the mechanism needs to be investigated further....

  20. CD3+CD8+CD161high Tc17 cells are depleted in HIV-infection

    DEFF Research Database (Denmark)

    Gaardbo, Julie Christine; Hartling, Hans Jakob; Thorsteinsson, Kristina

    2012-01-01

    CD8+ Tc17 cells with pro-inflammatory properties have only recently been acknowledged, and Tc17 cells in HIV-infection are undescribed. CD3+CD8+CD161 Tc17 cells and the production of Interleukin-17 were examined in untreated and treated HIV-infected patients, HIV-HCV co-infected patients...... and healthy controls. Depletion of CD3+CD8+CD161 Tc17 cells and diminished production of Interleukin-17 in HIV-infected patients was found. The level of Tc17 cells was associated with the level of the CD4+ count in treated patients....

  1. Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells.

    Science.gov (United States)

    Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C; Van Duyne, Rachel; Calvert, Valerie; Petricoin, Emanuel; Saifuddin, Mohammed; Kehn-Hall, Kylene; Kashanchi, Fatah

    2015-06-01

    Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high-throughput proteomic assays, we have previously identified Bruton's tyrosine kinase (BTK) as a host protein that was uniquely upregulated in the plasma membrane of human immunodeficiency virus (HIV-1)-infected T cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant upregulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells; however, new BTK protein complexes were identified and distributed in both high molecular weight (∼600 kDa) and a small molecular weight complex (∼60-120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1-infected cells using small interfering RNA (siRNA) resulted in selective death of infected, but not uninfected, cells. Using BTK-specific antibody and small-molecule inhibitors including LFM-A13 and a FDA-approved compound, ibrutinib (PCI-32765), we have found that HIV-1-infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1-infected cells are sensitive to treatments targeting BTK expressed in infected cells.

  2. Role of Bruton’s Tyrosine Kinase inhibitors in HIV-1 infected cells

    Science.gov (United States)

    Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C; Van Duyne, Rachel; Calvert, Valerie; Petricoin, Emanuel; Saifuddin, Mohammed; Kehn-Hall, Kylene; Kashanchi, Fatah

    2015-01-01

    Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high throughput proteomic assays, we have previously identified Bruton’s tyrosine kinase (BTK) as a host protein that was uniquely up-regulated in the plasma membrane of HIV-1 infected T-cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant up-regulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells, however new BTK protein complexes were identified and distributed in both high molecular weight (~600 kDa) and a small molecular weight complex (~60–120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1 infected cells using siRNA resulted in selective death of infected, but not uninfected, cells. Using BTK specific antibody and small molecule inhibitors including LFM-A13 and a FDA approved compound, Ibrutinib (PCI – 32765), we have found that HIV-1 infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1 infected cells are sensitive to treatments targeting BTK expressed in infected cells. PMID:25672887

  3. Mycoplasma agalactiae Induces Cytopathic Effects in Infected Cells Cultured In Vitro.

    Directory of Open Access Journals (Sweden)

    Shrilakshmi Hegde

    Full Text Available Mycoplasma agalactiae is the etiological agent of the contagious agalactia syndrome in sheep and goats and causes significant economic losses worldwide. Yet the mechanism of pathogenesis is largely unknown. Even whole-genome sequence analysis of its pathogenic type strain did not lead to any conclusions regarding its virulence or pathogenicity factors. Although inflammation and tissue destruction at the local site of M. agalactiae infection are largely considered as effects of the host immune response, the direct effect of the agent on host cells is not completely understood. The aim of this study was to investigate the effect of M. agalactiae infection on the quality and viability of host cells in vitro. Changes in cell morphology including cell elongation, cytoplasm shrinkage and membrane blebbing were observed in infected HeLa cells. Chromatin condensation and increased caspase-3 cleavage in infected HeLa cells 48 h after infection suggests an apoptosis-like phenomenon in M. agalactiae-infected cells. In compliance with these results, decreased viability and cell lysis of M. agalactiae-infected HeLa cells was also observed. Measurement of the amount of LDH released after M. agalactiae infection revealed a time- and dose-dependent increase in HeLa cell lysis. A significant decrease in LDH released after gentamicin treatment of infected cells confirmed the major role of cytadherent M. agalactiae in inducing host cell lysis. This is the first study illustrating M. agalactiae's induction of cytopathic effects in infected HeLa cells. Further detailed investigation of infected host tissue for apoptotic markers might demonstrate the association between M. agalactiae-induced host cell lysis and the tissue destruction observed during M. agalactiae natural infection.

  4. Targeted sorting of single virus-infected cells of the coccolithophore Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Joaquín Martínez Martínez

    Full Text Available Discriminating infected from healthy cells is the first step to understanding the mechanisms and ecological implications of viral infection. We have developed a method for detecting, sorting, and performing molecular analysis of individual, infected cells of the important microalga Emiliania huxleyi, based on known physiological responses to viral infection. Of three fluorescent dyes tested, FM 1-43 (for detecting membrane blebbing gave the most unequivocal and earliest separation of cells. Furthermore, we were able to amplify the genomes of single infected cells using Multiple Displacement Amplification. This novel method to reliably discriminate infected from healthy cells in cultures will allow researchers to answer numerous questions regarding the mechanisms and implications of viral infection of E. huxleyi. The method may be transferable to other virus-host systems.

  5. Targeted sorting of single virus-infected cells of the coccolithophore Emiliania huxleyi.

    Science.gov (United States)

    Martínez Martínez, Joaquín; Poulton, Nicole J; Stepanauskas, Ramunas; Sieracki, Michael E; Wilson, William H

    2011-01-01

    Discriminating infected from healthy cells is the first step to understanding the mechanisms and ecological implications of viral infection. We have developed a method for detecting, sorting, and performing molecular analysis of individual, infected cells of the important microalga Emiliania huxleyi, based on known physiological responses to viral infection. Of three fluorescent dyes tested, FM 1-43 (for detecting membrane blebbing) gave the most unequivocal and earliest separation of cells. Furthermore, we were able to amplify the genomes of single infected cells using Multiple Displacement Amplification. This novel method to reliably discriminate infected from healthy cells in cultures will allow researchers to answer numerous questions regarding the mechanisms and implications of viral infection of E. huxleyi. The method may be transferable to other virus-host systems.

  6. Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs

    DEFF Research Database (Denmark)

    Birck, Malene Muusfeldt; Saraste, Antti; Hyttel, Poul

    2013-01-01

    Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia...

  7. Changes in NK and NKT cells in mesenteric lymph nodes after a Schistosoma japonicum infection.

    Science.gov (United States)

    Luo, Xueping; Xie, Hongyan; Chen, Dianhui; Yu, Xiuxue; Wu, Fan; Li, Lu; Wu, Changyou; Huang, Jun

    2014-03-01

    The mesenteric lymph node (MLN) is the main draining lymph node in mouse enterocoelia, which contains many types of immune cells. Among these cells, natural killer (NK) and natural killer T (NKT) cells belong to innate lymphoid cells (ILCs), which have potent activities for controlling a variety of pathogenic infections. In this study, C57BL/6 mice were infected with Schistosoma japonicum for 5-7 weeks. Lymphocytes were isolated from the MLN to detect changes in the phenotype and function of NK and NKT cells using a fluorescence activating cell sorter (FACS). These results demonstrated that a S. japonicum infection could significantly increase the percentage of NK cells in the mouse MLN, (P cell number of both NK and NKT cells. In addition, we found that NK and NKT cells from infected mice expressed higher levels of CD69 compared to normal mice (P NKT cell activation. Moreover, we found that the expression of CD4 was increased in infected MLN NK cells (P NKT cells of infected mice after phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation (P NKT cells might play roles in modulating the classical T cell response. Finally, our results indicated that the expression of CD94 was decreased in NK cells, suggesting that the downregulation of CD94 expression might served as a mechanism in NK cell activation.

  8. Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

    Energy Technology Data Exchange (ETDEWEB)

    Tilden, A.B.; Cauda, R.; Grossi, C.E.; Balch, C.M.; Lakeman, A.D.; Whitley, R.J.

    1986-06-01

    Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

  9. Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated inhibition of Yersinia enterocolitica infection.

    Directory of Open Access Journals (Sweden)

    Alexandra Wittmann

    Full Text Available In industrialized countries bacterial intestinal infections are commonly caused by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with the host immune system determines the adequacy of an appropriate response against pathogens. In this study we addressed whether the probiotic Bifidobacterium adolescentis is protective during intestinal Yersinia enterocolitica infection. Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia enterocolitica. B. adolescentis fed and Yersinia infected mice were protected from Yersinia infection as indicated by a significantly reduced weight loss and splenic Yersinia load when compared to Yersinia infected mice. Moreover, protection from infection was associated with increased intestinal plasmacytoid dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting B. adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody, to deplete plasmacytoid dendritic cells, or respective isotype control. The B. adolescentis-mediated protection from Yersinia dissemination to the spleen was abrogated after plasmacytoid dendritic cell depletion indicating a crucial function for pDC in control of intestinal Yersinia infection. We suggest that feeding of B. adolescentis modulates the intestinal immune system in terms of increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which might account for the B. adolescentis-mediated protection from Yersinia enterocolitica infection.

  10. Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated inhibition of Yersinia enterocolitica infection.

    Science.gov (United States)

    Wittmann, Alexandra; Autenrieth, Ingo B; Frick, Julia-Stefanie

    2013-01-01

    In industrialized countries bacterial intestinal infections are commonly caused by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with the host immune system determines the adequacy of an appropriate response against pathogens. In this study we addressed whether the probiotic Bifidobacterium adolescentis is protective during intestinal Yersinia enterocolitica infection. Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia enterocolitica. B. adolescentis fed and Yersinia infected mice were protected from Yersinia infection as indicated by a significantly reduced weight loss and splenic Yersinia load when compared to Yersinia infected mice. Moreover, protection from infection was associated with increased intestinal plasmacytoid dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting B. adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody, to deplete plasmacytoid dendritic cells, or respective isotype control. The B. adolescentis-mediated protection from Yersinia dissemination to the spleen was abrogated after plasmacytoid dendritic cell depletion indicating a crucial function for pDC in control of intestinal Yersinia infection. We suggest that feeding of B. adolescentis modulates the intestinal immune system in terms of increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which might account for the B. adolescentis-mediated protection from Yersinia enterocolitica infection.

  11. Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

    International Nuclear Information System (INIS)

    Hoever, Gerold; Vogel, Jens-Uwe; Lukashenko, Polina; Hofmann, Wolf-Karsten; Komor, Martina; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2005-01-01

    In a model of human neuroblastoma (NB) cell lines persistently infected with human cytomegalovirus (HCMV) we previously showed that persistent HCMV infection is associated with an increased malignant phenotype, enhanced drug resistance, and invasive properties. To gain insights into the mechanisms of increased malignancy we analyzed the global changes in cellular gene expression induced by persistent HCMV infection of human neuroblastoma cells by use of high-density oligonucleotide microarrays (HG-U133A, Affymetrix) and RT-PCR. Comparing the gene expression of different NB cell lines with persistently infected cell sub-lines revealed 11 host cell genes regulated in a similar manner throughout all infected samples. Nine of these 11 genes may contribute to the previously observed changes in malignant phenotype of persistently HCMV infected NB cells by influencing invasive growth, apoptosis, angiogenesis, and proliferation. Thus, this work provides the basis for further functional studies

  12. Reactive oxygen species induced by Streptococcus pyogenes invasion trigger apoptotic cell death in infected epithelial cells.

    Science.gov (United States)

    Aikawa, Chihiro; Nozawa, Takashi; Maruyama, Fumito; Tsumoto, Kohei; Hamada, Shigeyuki; Nakagawa, Ichiro

    2010-06-01

    Streptococcus pyogenes (group A streptococcus, GAS), one of the most common pathogens of humans, attaches and invades into human pharyngeal or skin epithelial cells. We have previously reported that induction of apoptosis is associated with GAS invasion, which induces mitochondrial dysfunction and apoptotic cell death. We demonstrate here that GAS-induced apoptosis is mediated by reactive oxygen species (ROS) production. Both the induction of apoptosis and ROS production markedly increased upon invasion of wild-type GAS strain JRS4 into HeLa cells; however, the apoptotic response was not observed in fibronectin-binding protein F1-disrupted mutant SAM1-infected cells. In Bcl-2-overexpressing HeLa cells (HBD98-2-4), the induction of apoptosis, ROS production and mitochondrial dysfunction were significantly suppressed, whereas the numbers of invaded GAS was not different between HeLa (mock cells) and the HeLa HBD98-2-4 cells. Whereas Rac1 activation occurred during GAS invasion, ROS production in GAS-infected cells was clearly inhibited by transfection with the Rac1 mutants (L37 or V12L37), but not by the dominant active mutant (V12L61) or by the dominant negative mutant (N17). These observations indicate that GAS invasion triggers ROS production through Rac1 activation and generated ROS induced mitochondrial dysfunction leading to cellular apoptosis.

  13. Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity

    OpenAIRE

    Jansen, C.A.; de Geus, E.D.; van Haarlem, D.A.; van de Haar, P.M.; Löndt, B.Z; Graham, S.P.; Göbel, T.W.; van Eden, W.; Brookes, S.M.; Vervelde, L.

    2013-01-01

    Infection of chickens with low pathogenicity avian influenza (LPAI) virus results in mild clinical signs while infection with highly pathogenic avian influenza (HPAI) viruses causes death of the birds within 36–48 hours. Since natural killer (NK) cells have been shown to play an important role in influenza-specific immunity, we hypothesise that NK cells are involved in this difference in pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus infection was studied. Next...

  14. Virus specific antigens in mammalian cells infected with herpes simplex virus

    Science.gov (United States)

    Watson, D. H.; Shedden, W. I. H.; Elliot, A.; Tetsuka, T.; Wildy, P.; Bourgaux-Ramoisy, D.; Gold, E.

    1966-01-01

    Antisera to specific proteins in herpes simplex infected cells were produced by immunization of rabbits with infected rabbit kidney cells. These antisera were highly virus specific and produced up to twelve lines in immunodiffusion tests against infected cell extracts. Acrylamide electrophoresis and immunoelectrophoresis revealed up to ten virus specific proteins of varying size. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:4288648

  15. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  16. Adrenaline-induced mobilization of T cells in HIV-infected patients

    DEFF Research Database (Denmark)

    Søndergaard, S R; Cozzi-Lepri, A; Ullum, H

    2000-01-01

    The present study aimed to investigate lymphocyte mobilization from peripheral cell reservoirs in HIV-infected patients. Nine HIV-infected patients on stable highly active anti-retroviral therapy (HAART), eight treatment-naive HIV-infected patients and eight HIV- controls received a 1-h adrenaline...... infusion. The adrenaline infusion induced a three-fold increase in the concentration of lymphocytes in all three groups. All HIV-infected patients mobilized significantly higher numbers of CD8+ cells but less CD4+ cells. All subjects mobilized CD45RA+CD62L+ and CD8+CD28+ cells to a lesser extent than CD45......RO+CD45RA- and CD8+CD28-cells. Furthermore, high numbers of CD8+CD38+ cells were mobilized only in the HIV-infected patients. It was therefore predominantly T cells with an activated phenotype which were mobilized after adrenaline stimulation. It is concluded that the HIV-associated immune defect...

  17. Sickle cell children traveling abroad: primary risk is infection.

    Science.gov (United States)

    Runel-Belliard, Camille; Lesprit, Emmanuelle; Quinet, Béatrice; Grimprel, Emmanuel

    2009-01-01

    Pediatricians taking care of sickle cell children in France are concerned about giving travel advice. Very few articles are published and no study has been done about it. A lot of pediatricians are using their own experience to decide if sickle cell children can travel abroad. Studying the consequences of such travel for sickle cell children is important to discuss common recommendations. We conducted a prospective study from June 2006 to December 2007 on desires to travel expressed during our consultations with sickle cell children. We studied notable events that occurred during travel and at least 2 months after return. Of 52 desires to travel, 10 were cancelled. All of the 42 trips were to Africa. Median duration of travel was 1.29 months (0.5-3). Median age at travel was 7.6 years (0.2-17.7). Events during travel were two hospitalizations (4.8%), a transfusion (2.4%), and four paramedical or medical examinations (9.6%). After return, four events occurred: two SS children had Plasmodium falciparum malaria (4.8%) and two had digestive bacteremia (4.8%) in SC and Sbeta+ children. No event occurred during plane travel. None of our patients died. The primary risk for sickle cell children traveling to Africa is infection: malaria first and digestive septicemia second. These risks are increased by long travel and poor sanitary conditions. Each travel should be prepared a long time before departure, and each pediatrician should insist on malaria prophylaxis and sanitary conditions, especially for young children. Trips should be shorter than 1 month when possible. A longer prospective study will be done to confirm these results.

  18. High content image based analysis identifies cell cycle inhibitors as regulators of Ebola virus infection.

    Science.gov (United States)

    Kota, Krishna P; Benko, Jacqueline G; Mudhasani, Rajini; Retterer, Cary; Tran, Julie P; Bavari, Sina; Panchal, Rekha G

    2012-09-25

    Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

  19. High Content Image Based Analysis Identifies Cell Cycle Inhibitors as Regulators of Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Sina Bavari

    2012-09-01

    Full Text Available Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

  20. Analysis of gene expression in fetal and adult cells infected with rubella virus

    International Nuclear Information System (INIS)

    Adamo, Maria Pilar; Zapata, Marta; Frey, Teryl K.

    2008-01-01

    Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asis, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced

  1. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier

    2017-12-01

    Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

  2. CD4 T Cell Responses in Latent and Chronic Viral Infections

    Science.gov (United States)

    Walton, Senta; Mandaric, Sanja; Oxenius, Annette

    2013-01-01

    The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

  3. Mycoplasma orale infection affects K+ and Cl- currents in the HSG salivary gland cell line.

    Science.gov (United States)

    Izutsu, K T; Fatherazi, S; Belton, C M; Oda, D; Cartwright, F D; Kenny, G E

    1996-06-01

    The relations between K+ channel and Cl- channel currents and mycoplasma infection status were studied longitudinally in HSG cells, a human submandibular gland cell line. The K+ channel currents were disrupted by the occurrence of mycoplasma infection: muscarinic activation of K+ channels and K+ channel expression as estimated by ionomycin- or hypotonically induced K+ current responses were all decreased. Similar decreases in ionomycin- and hypotonically induced responses were observed for Cl- channels, but only the latter decrease was statistically significant. Also, Cl- currents could be elicited more frequently than K+ currents (63% of cases versus 0%) in infected cells when tested by exposure to hypotonic media, indicating that mycoplasma infection affects K+ channels relatively more than Cl- channels. These changes occurred in the originally infected cells, were ameliorated when the infection was cleared with sparfloxacin, and recurred when the cells were reinfected. Such changes would be expected to result in hyposecretion of salivary fluid if they occurred in vivo.

  4. Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease.

    Science.gov (United States)

    Morrissey, Benita J; Bycroft, Thomas P; Almossawi, Ofran; Wilkey, Olufunke B; Daniels, Justin G

    2015-01-01

    Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5 °C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p = 0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.

  5. Biosynthesis of measles virus hemagglutinin in persistently infected cells

    International Nuclear Information System (INIS)

    Bellini, W.J.; Silver, G.D.; McFarlin, D.E.

    1983-01-01

    The synthesis of the hemagglutinin (HA) glycoprotein of measles virus was investigated in a persistently infected cell line using a monoclonal anti-HA. The synthesis of the HA protein was shown to be associated with the rough endoplasmic reticulum. The unglycosylated (HA 0 ) apoprotein is synthesized as a 65.000 dalton peptide and is inserted into the rough endoplasmic reticulum as a transmembrane protein with approximately 2 to 3000 daltons of the peptide exposed to the cytoplasmic membrane surface. Primary glycosylation of the HA protein was found to occur through the lipid-linked carrier, dolichol-phosphate, as determined by inhibition of glycosylation by tunicamycin. Glycosylation, however, was not a prerequisite for membrane insertion. Endo-β-N-acetyl-Glucosaminidase H digestion of the fully glycosylated HA protein indicated that both simple and complex oligosaccharides are present on the surface glycoprotein. (Author)

  6. CD154 costimulated ovine primary B cells, a cell culture system that supports productive infection by bovine leukemia virus.

    Science.gov (United States)

    Van den Broeke, A; Cleuter, Y; Beskorwayne, T; Kerkhofs, P; Szynal, M; Bagnis, C; Burny, A; Griebel, P

    2001-02-01

    Bovine leukemia virus (BLV) is closely associated with the development of B-cell leukemia and lymphoma in cattle. BLV infection has also been studied extensively in an in vivo ovine model that provides a unique system for studying B-cell leukemogenesis. There is no evidence that BLV can directly infect ovine B cells in vitro, and there are no direct data regarding the oncogenic potential of the viral Tax transactivator in B cells. Therefore, we developed ovine B-cell culture systems to study the interaction between BLV and its natural target, the B cell. In this study, we used murine CD154 (CD40 ligand) and gamma-chain-common cytokines to support the growth of B cells isolated from ovine lymphoid tissues. Integrated provirus, extrachromosomal forms, and viral transcripts were detected in BLV-exposed populations of immature, rapidly dividing surface immunoglobulin M-positive B cells from sheep ileal Peyer's patches and also in activated mature B cells isolated from blood. Conclusive evidence of direct B-cell infection by BLV was obtained through the use of cloned B cells derived from sheep jejunal Peyer's patches. Finally, inoculation of sheep with BLV-infected cultures proved that infectious virus was shed from in vitro-infected B cells. Collectively, these data confirm that a variety of ovine B-cell populations can support productive infection by BLV. The development of ovine B-cell cultures permissive for BLV infection provides a controlled system for investigating B-cell leukemogenic processes and the pathogenesis of BLV infection.

  7. Cytotoxic potential of decidual NK cells and CD8+ T cells awakened by infections.

    Science.gov (United States)

    Crespo, Ângela C; van der Zwan, Anita; Ramalho-Santos, João; Strominger, Jack L; Tilburgs, Tamara

    2017-02-01

    To establish a healthy pregnancy the maternal immune system must tolerate fetal allo-antigens, yet remain competent to respond to infections. The ability of decidual NK cells (dNK) to promote migration of fetal extravillous trophoblasts (EVT) and placental growth as well as the capacity of EVT to promote immune tolerance are topics of high interest and extensive research. However, the problem of how dNK and decidual CD8+ T cells (CD8+ dT) provide immunity to infections of the placenta and the mechanisms that regulate their cytolytic function has thus far largely been ignored. Fetal EVT are the most invasive cells of the placenta and directly interact with maternal decidual immune cells at this maternal-fetal interface. Besides the expression of non-polymorphic HLA-E and HLA-G molecules that are associated with immune tolerance, EVT also express highly polymorphic HLA-C molecules that can serve as targets for maternal dNK and CD8+ dT responses. HLA-C expression by EVT has a dual role as the main molecule to which immune tolerance needs to be established and as the only molecule that can present pathogen-derived peptides and provide protective immunity when EVT are infected. The focus of this review is to address the regulation of cytotoxicity of dNK and CD8+ dT, which is essential for maternal-fetal immune tolerance as well as recent evidence that both cell types can provide immunity to infections at the maternal-fetal interface. A particular emphasis is given to the role of HLA-C expressed by EVT and its capacity to elicit dNK and CD8+ dT responses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Melisa Gorosito Serrán

    2017-11-01

    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able

  9. Parasitic infection improves survival from septic peritonitis by enhancing mast cell responses to bacteria in mice.

    Directory of Open Access Journals (Sweden)

    Rachel E Sutherland

    Full Text Available Mammals are serially infected with a variety of microorganisms, including bacteria and parasites. Each infection reprograms the immune system's responses to re-exposure and potentially alters responses to first-time infection by different microorganisms. To examine whether infection with a metazoan parasite modulates host responses to subsequent bacterial infection, mice were infected with the hookworm-like intestinal nematode Nippostrongylus brasiliensis, followed in 2-4 weeks by peritoneal injection of the pathogenic bacterium Klebsiella pneumoniae. Survival from Klebsiella peritonitis two weeks after parasite infection was better in Nippostrongylus-infected animals than in unparasitized mice, with Nippostrongylus-infected mice having fewer peritoneal bacteria, more neutrophils, and higher levels of protective interleukin 6. The improved survival of Nippostrongylus-infected mice depends on IL-4 because the survival benefit is lost in mice lacking IL-4. Because mast cells protect mice from Klebsiella peritonitis, we examined responses in mast cell-deficient Kit(W-sh/Kit(W-sh mice, in which parasitosis failed to improve survival from Klebsiella peritonitis. However, adoptive transfer of cultured mast cells to Kit(W-sh/Kit(W-sh mice restored survival benefits of parasitosis. These results show that recent infection with Nippostrongylus brasiliensis protects mice from Klebsiella peritonitis by modulating mast cell contributions to host defense, and suggest more generally that parasitosis can yield survival advantages to a bacterially infected host.

  10. IMMUNITY TO INFECTIONS AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Franco Aversa

    2016-10-01

    Full Text Available The advantage of using a Human Leukocyte Antigen (HLA-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT has at least one family member with whom shares one haplotype (haploidentical and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD. Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT  has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs, others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY. Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs.  Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC   showed promise in decreasing early transplant-related mortality (TRM, and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

  11. Follicular Helper T Cells are Essential for the Elimination of Plasmodium Infection

    Directory of Open Access Journals (Sweden)

    Damián Pérez-Mazliah

    2017-10-01

    Full Text Available CD4+ follicular helper T (Tfh cells have been shown to be critical for the activation of germinal center (GC B-cell responses. Similar to other infections, Plasmodium infection activates both GC as well as non-GC B cell responses. Here, we sought to explore whether Tfh cells and GC B cells are required to eliminate a Plasmodium infection. A CD4 T cell-targeted deletion of the gene that encodes Bcl6, the master transcription factor for the Tfh program, resulted in complete disruption of the Tfh response to Plasmodium chabaudi in C57BL/6 mice and consequent disruption of GC responses and IgG responses and the inability to eliminate the otherwise self-resolving chronic P. chabaudi infection. On the other hand, and contrary to previous observations in immunization and viral infection models, Signaling Lymphocyte Activation Molecule (SLAM-Associated Protein (SAP-deficient mice were able to activate Tfh cells, GC B cells, and IgG responses to the parasite. This study demonstrates the critical role for Tfh cells in controlling this systemic infection, and highlights differences in the signals required to activate GC B cell responses to this complex parasite compared with those of protein immunizations and viral infections. Therefore, these data are highly pertinent for designing malaria vaccines able to activate broadly protective B-cell responses.

  12. Identification of a Monocyte Receptor on Herpesvirus-Infected Endothelial Cells

    Science.gov (United States)

    Etingin, Orli R.; Silverstein, Roy L.; Hajjar, David P.

    1991-08-01

    The adhesion of circulating blood cells to vascular endothelium may be an initial step in atherosclerosis, inflammation, and wound healing. One mechanism for promoting cell-cell adhesion involves the expression of adhesion molecules on the surface of the target cell. Herpes simplex virus infection of endothelium induces arterial injury and has been implicated in the development of human atherosclerosis. We now demonstrate that HSV-infected endothelial cells express the adhesion molecule GMP140 and that this requires cell surface expression of HSV glycoprotein C and local thrombin generation. Monocyte adhesion to HSV-infected endothelial cells was completely inhibited by anti-GMP140 antibodies but not by antibodies to other adhesion molecules such as VCAM and ELAM-1. The induction of GMP140 expression on HSV-infected endothelium may be an important pathophysiological mechanism in virus-induced cell injury and inflammation.

  13. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  14. Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle.

    Science.gov (United States)

    Shock, Jennifer L; Fischer, Kael F; DeRisi, Joseph L

    2007-01-01

    The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression. We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.

  15. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  16. Identification of XMRV infection-associated microRNAs in four cell types in culture.

    Directory of Open Access Journals (Sweden)

    Ketha V K Mohan

    Full Text Available INTRODUCTION: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC and chronic fatigue syndrome (CFS in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA, which regulate gene expression, were so far not identified in cells infected with XMRV in culture. METHODS: Two prostate cell lines (LNCaP and DU145 and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. RESULTS: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs. miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. DISCUSSION: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.

  17. Sub-nanosecond Half-life Measurement of the Yrast I{sup π}=5{sup −} State in the N=78 Nucleus {sup 136}{sub 58}Ce using Fast-timing Coincident Gamma-ray Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Alharbi, T. [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom); Department of Physics, Faculty of Science in Zulfi, Almajmaah University, P.O. Box 1712, 11932 (Saudi Arabia); Regan, P.H., E-mail: p.regan@surrey.ac.uk [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom); National Physical Laboratory, Teddington, Middlesex, TW11 0LW (United Kingdom); Mărginean, N. [Horia Hulubei – National Institute for Physics and Nuclear Engineering (IFIN-HH), Bucharest (Romania); Podolyák, Zs.; Bajoga, A.; Britton, R. [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom); Bucurescu, D.; Deleanu, D.; Filipescu, D.; Ghită, D.; Glodariu, T.; Mihai, C. [Horia Hulubei – National Institute for Physics and Nuclear Engineering (IFIN-HH), Bucharest (Romania); Mulholland, K. [School of Engineering, University of the West of Scotland, High Street, Paisley PA1 2BE (United Kingdom); Mărginean, R.; Negret, A.; Nita, C.R. [Horia Hulubei – National Institute for Physics and Nuclear Engineering (IFIN-HH), Bucharest (Romania); Patel, Z. [Department of Physics, University of Surrey, Guildford, GU2 7XH (United Kingdom); Roberts, O.J. [School of Computing Engineering and Mathematics, University of Brighton, Brighton, BN2 4GJ (United Kingdom); Stroe, L.; Sava, T. [Horia Hulubei – National Institute for Physics and Nuclear Engineering (IFIN-HH), Bucharest (Romania); and others

    2014-06-15

    We report on the measurement of the half-life of the yrast I{sup π}=5{sup −} state in the transitional nucleus {sup 136}Ce using a combined HPGe-LaBr3(Ce) scintillator gamma-ray detection array. The measured value for the E1 decay is approximately half a nanosecond, which corresponds to an E1 decay strength of approximately 2×10{sup −6} Wu. This value is in line with single-particle type E1 decays in this mass region and suggests no sign of additional K-hindrance associated with axially symmetric quadrupole deformations observed for lighter cerium isotopes.

  18. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Xiaozhen Liang

    2009-11-01

    Full Text Available Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68 gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners that do not directly participate in virus replication, but rather facilitate virus

  19. T-cell-dependent control of acute Giardia lamblia infections in mice.

    Science.gov (United States)

    Singer, S M; Nash, T E

    2000-01-01

    We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.

  20. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Science.gov (United States)

    Liang, Xiaozhen; Collins, Christopher M; Mendel, Justin B; Iwakoshi, Neal N; Speck, Samuel H

    2009-11-01

    Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68) gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency) account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners) that do not directly participate in virus replication, but rather facilitate virus reactivation by

  1. Natural Killer Cell Function and Dysfunction in Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Kayla A. Holder

    2014-01-01

    Full Text Available Viruses must continually adapt against dynamic innate and adaptive responses of the host immune system to establish chronic infection. Only a small minority (~20% of those exposed to hepatitis C virus (HCV spontaneously clear infection, leaving approximately 200 million people worldwide chronically infected with HCV. A number of recent research studies suggest that establishment and maintenance of chronic HCV infection involve natural killer (NK cell dysfunction. This relationship is illustrated in vitro by disruption of typical NK cell responses including both cell-mediated cytotoxicity and cytokine production. Expression of a number of activating NK cell receptors in vivo is also affected in chronic HCV infection. Thus, direct in vivo and in vitro evidence of compromised NK function in chronic HCV infection in conjunction with significant epidemiological associations between the outcome of HCV infection and certain combinations of NK cell regulatory receptor and class I human histocompatibility linked antigen (HLA genotypes indicate that NK cells are important in the immune response against HCV infection. In this review, we highlight evidence suggesting that selective impairment of NK cell activity is related to establishment of chronic HCV infection.

  2. Surfactant Protein D modulates HIV infection of both T-cells and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Jens Madsen

    Full Text Available Surfactant Protein D (SP-D is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo.

  3. B-Cell and T-Cell Immune Responses to Experimental Helicobacter pylori Infection in Humans

    Science.gov (United States)

    Nurgalieva, Zhannat Z.; Conner, Margaret E.; Opekun, Antone R.; Zheng, Carl Q.; Elliott, Susan N.; Ernst, Peter B.; Osato, Michael; Estes, Mary K.; Graham, David Y.

    2005-01-01

    The acute antibody and T-cell immune response to Helicobacter pylori infection in humans has not been studied systematically. Serum from H. pylori-naive volunteers challenged with H. pylori and cured after 4 or 12 weeks was tested by enzyme-linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM) and IgA established using bacterial lysates from homologous (the infecting strain) and heterologous H. pylori. Proteins recognized by IgM antibody were identified by mass spectrometry of immunoreactive bands separated by two-dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30 cells) were assessed by immunohistochemistry. All 18 infected volunteers developed H. pylori-specific IgM responses to both homologous or heterologous H. pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks postinfection. IgM Western blotting showed immunoreactivity of postinfection serum samples to multiple H. pylori proteins with molecular weights ranging between 9,000 (9K) to 150K with homologous strains but only a 70K band using heterologous antigens. Two-dimensional electrophoresis demonstrated that production of H. pylori-specific IgM antibodies was elicited by H. pylori flagellins A and B, urease B, ABC transporter binding protein, heat shock protein 70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell numbers increased following infection. IgM antibody responses were detected to a range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority of H. pylori proteins were those involved in motility and colonization and may represent targets for vaccine development. PMID:15845507

  4. Alterations in the nuclear proteome of HIV-1 infected T-cells

    Energy Technology Data Exchange (ETDEWEB)

    DeBoer, Jason [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Jagadish, Teena; Haverland, Nicole A. [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Ciborowski, Pawel [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States)

    2014-11-15

    Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.

  5. Alterations in the nuclear proteome of HIV-1 infected T-cells

    International Nuclear Information System (INIS)

    DeBoer, Jason; Jagadish, Teena; Haverland, Nicole A.; Madson, Christian J.; Ciborowski, Pawel; Belshan, Michael

    2014-01-01

    Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines

  6. Retroviral infection of non-dividing cells: Old and new perspectives

    International Nuclear Information System (INIS)

    Yamashita, Masahiro; Emerman, Michael

    2006-01-01

    The dependence of retroviral replication on cell proliferation was described as early as 1958, although different classes of retroviruses are able to infect non-dividing cells with different efficiencies. For example, the human immunodeficiency virus (HIV) and other lentiviruses infect most non-dividing cells nearly as well as dividing cells, while the gammaretroviruses such as the murine leukemia virus (MLV) cannot infect non-dividing cells, and other retroviruses have intermediate phenotypes. One exception to the ability of HIV to infect non-dividing cells involves resting CD4+ T cells in vitro where there are multiple restrictions. However, recent data show that there is massive infection of non-activated CD4+ T cell during acute infection which suggests that the situation is different in vivo. Finally, much work trying to explain the difference between HIV and MLV in non-dividing cells has focused on describing the ability of HIV to enter the nucleus during interphase. However, we suggest that events in the viral lifecycle other than nuclear import may be more important in determining the ability of a given retrovirus to infect non-dividing cells

  7. Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo

    Directory of Open Access Journals (Sweden)

    Pinatel Christiane

    2010-03-01

    Full Text Available Abstract Background Adult T cell leukemia results from the malignant transformation of a CD4+ lymphoid clone carrying an integrated HTLV-1 provirus that has undergone several oncogenic events over a 30-60 year period of persistent clonal expansion. Both CD4+ and CD8+ lymphocytes are infected in vivo; their expansion relies on CD4+ cell cycling and on the prevention of CD8+ cell death. Cloned infected CD4+ but not CD8+ T cells from patients without malignancy also add up nuclear and mitotic defects typical of genetic instability related to theexpression of the virus-encoded oncogene tax. HTLV-1 expression is cancer-prone in vitro, but in vivo numerous selection forces act to maintain T cell homeostasis and are possibly involved in clonal selection. Results Here we demonstrate that the HTLV-1 associated CD4+ preleukemic phenotype and the specific patterns of CD4+ and CD8+ clonal expansion are in vivo selected processes. By comparing the effects of recent (1 month experimental infections performed in vitro and those observed in cloned T cells from patients infected for >6-26 years, we found that in chronically HTLV-1 infected individuals, HTLV-1 positive clones are selected for tax expression. In vivo, infected CD4+ cells are positively selected for cell cycling whereas infected CD8+ cells and uninfected CD4+ cells are negatively selected for the same processes. In contrast, the known HTLV-1-dependent prevention of CD8+ T cell death pertains to both in vivo and in vitro infected cells. Conclusions Therefore, virus-cell interactions alone are not sufficient to initiate early leukemogenesis in vivo.

  8. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  9. Epstein-Barr Virus Type 2 Infects T Cells in Healthy Kenyan Children.

    Science.gov (United States)

    Coleman, Carrie B; Daud, Ibrahim I; Ogolla, Sidney O; Ritchie, Julie A; Smith, Nicholas A; Sumba, Peter O; Dent, Arlene E; Rochford, Rosemary

    2017-09-15

    The 2 strains of Epstein-Barr virus (EBV), EBV type 1 (EBV-1) and EBV-2, differ in latency genes, suggesting that they use distinct mechanisms to establish latency. We previously reported that EBV-2 infects T cells in vitro. In this study, we tested the possibility that EBV-2 infects T cells in vivo. Purified T-cell fractions isolated from children positive for EBV-1 or EBV-2 and their mothers were examined for the presence of EBV and for EBV type. We detected EBV-2 in all T-cell samples obtained from EBV-2-infected children at 12 months of age, with some children retaining EBV-2-positive T cells through 24 months of age, suggesting that EBV-2 persists in T cells. We were unable to detect EBV-2 in T-cell samples from mothers but could detect EBV-2 in samples of their breast milk and saliva. These data suggest that EBV-2 uses T cells as an additional latency reservoir but that, over time, the frequency of infected T cells may drop below detectable levels. Alternatively, EBV-2 may establish a prolonged transient infection in the T-cell compartment. Collectively, these novel findings demonstrate that EBV-2 infects T cells in vivo and suggest EBV-2 may use the T-cell compartment to establish latency. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

    Directory of Open Access Journals (Sweden)

    William G C Horsnell

    2013-10-01

    Full Text Available In this study, B cell function in protective T(H2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.

  11. Lysis of endogenously infected CD4+ T cell blasts by rIL-2 activated autologous natural killer cells from HIV-infected viremic individuals.

    Directory of Open Access Journals (Sweden)

    Manuela Fogli

    2008-07-01

    Full Text Available Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research. In vitro studies have shown that natural killer (NK cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cell blasts exogenously infected with several strains of HIV-1. However, it is not known whether the deleterious effects of high HIV-1 viremia interferes with the NK cell-mediated cytolysis of autologous, endogenously HIV-1-infected CD4+ T cells. Here, we stimulate primary CD4+ T cells, purified ex vivo from HIV-1-infected viremic patients, with PHA and rIL2 (with or without rIL-7. This experimental procedure allows for the significant expansion and isolation of endogenously infected CD4+ T cell blasts detected by intracellular staining of p24 HIV-1 core antigen. We show that, subsequent to the selective down-modulation of MHC class-I (MHC-I molecules, HIV-1-infected p24(pos blasts become partially susceptible to lysis by rIL-2-activated NK cells, while uninfected p24(neg blasts are spared from killing. This NK cell-mediated killing occurs mainly through the NKG2D activation pathway. However, the degree of NK cell cytolytic activity against autologous, endogenously HIV-1-infected CD4+ T cell blasts that down-modulate HLA-A and -B alleles and against heterologous MHC-I(neg cell lines is particularly low. This phenomenon is associated with the defective surface expression and engagement of natural cytotoxicity receptors (NCRs and with the high frequency of the anergic CD56(neg/CD16(pos subsets of highly dysfunctional NK cells from HIV-1-infected viremic patients. Collectively, our data demonstrate that the chronic viral replication of HIV-1 in infected individuals results in several phenotypic and functional aberrancies that interfere with the NK cell-mediated killing of autologous p24(pos blasts derived from primary T cells.

  12. T cells for viral infections after allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Bollard, Catherine M; Heslop, Helen E

    2016-06-30

    Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

  13. Cell migration is another player of the minute virus of mice infection

    Energy Technology Data Exchange (ETDEWEB)

    Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

    2014-11-15

    The parvovirus minute virus of mice, prototype strain (MVMp), preferentially infects and kills cancer cells. This intrinsic MVMp oncotropism may depend in part on the early stages of MVMp infection. To test this hypothesis, we investigated the early events of MVMp infection in mouse LA9 fibroblasts and a highly invasive mouse mammary tumor cell line derived from polyomavirus middle T antigen-mediated transformation. Using a combination of fluorescence and electron microscopy, we found that various parameters of the cell migration process affect MVMp infection. We show that, after binding to the plasma membrane, MVMp particles rapidly cluster at the leading edge of migrating cells, which exhibit higher levels of MVMp uptake than non-motile cells. Moreover, promoting cell migration on a fibronectin matrix increased MVMp infection, and induction of epithelial–mesenchymal transition allowed MVMp replication in non-permissive epithelial cells. Hence, we propose that cell migration influences the early stages of MVMp infection. - Highlights: • We document early steps of MVMp infection. • We report that a fibronectin matrix promotes MVMp infection. • We show that cellular migration plays a role in MVMp uptake. • We show that epithelial–mesenchymal transition allows MVMp replication.

  14. Cell migration is another player of the minute virus of mice infection

    International Nuclear Information System (INIS)

    Garcin, Pierre O.; Panté, Nelly

    2014-01-01

    The parvovirus minute virus of mice, prototype strain (MVMp), preferentially infects and kills cancer cells. This intrinsic MVMp oncotropism may depend in part on the early stages of MVMp infection. To test this hypothesis, we investigated the early events of MVMp infection in mouse LA9 fibroblasts and a highly invasive mouse mammary tumor cell line derived from polyomavirus middle T antigen-mediated transformation. Using a combination of fluorescence and electron microscopy, we found that various parameters of the cell migration process affect MVMp infection. We show that, after binding to the plasma membrane, MVMp particles rapidly cluster at the leading edge of migrating cells, which exhibit higher levels of MVMp uptake than non-motile cells. Moreover, promoting cell migration on a fibronectin matrix increased MVMp infection, and induction of epithelial–mesenchymal transition allowed MVMp replication in non-permissive epithelial cells. Hence, we propose that cell migration influences the early stages of MVMp infection. - Highlights: • We document early steps of MVMp infection. • We report that a fibronectin matrix promotes MVMp infection. • We show that cellular migration plays a role in MVMp uptake. • We show that epithelial–mesenchymal transition allows MVMp replication

  15. Clearance of Giardia muris infection in mice deficient in natural killer cells.

    OpenAIRE

    Heyworth, M F; Kung, J E; Eriksson, E C

    1986-01-01

    Immunocompetent C57BL/6J mice and beige mice (which are deficient in natural killer cells) were infected with Giardia muris. Both types of mice cleared G. muris infection at similar rates. This observation suggests that clearance of G. muris parasites from the mouse intestine is not mediated by natural killer cells.

  16. T-cell dynamics in healthy and HIV-infected individuals

    NARCIS (Netherlands)

    Vrisekoop, N.

    2007-01-01

    This thesis focuses on T-cell dynamics in healthy and both treated and untreated HIV-infected individuals. Although the progressive decline in CD4+ T-cell numbers is the hallmark of HIV infection, the mechanisms behind this depletion remain controversial. Currently the most prevailing ideas include

  17. Membrane prteins of herpes simplex infected cells. Immunological and biochemical studies

    NARCIS (Netherlands)

    Welling-Wester, Sijtske

    1981-01-01

    As a consequence of infection with herpes simplex virus (HSV), cells exhibit a number of alterations. One of these is expressed as a change in the polypeptide composition of the surface of the infected cells. In this study several methods used for the isolation of these polypeptides expressed on the

  18. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    Science.gov (United States)

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

  19. Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

    Science.gov (United States)

    Katri, Patricia; Ruan, Shigui

    2004-11-01

    Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

  20. Measles virus polypeptides in purified virions and in infected cells

    International Nuclear Information System (INIS)

    Vainionpaeae, R.; Ziola, B.; Salmi, A.

    1978-01-01

    A wild-type measles virus was radiolabeled during growth in VERO cells and purified by two successive potassium tartrate gradient centrifugations. The virion polypeptide composition was determined by SDS-polyacrylamide gel electrophoresis employing two different buffer systems. Six virus-specific polypeptides were consistently detected. The largest (L) had a molecular weight (MW) of greater than 150,000. The second largest polypeptide, G (MW 79,000), was the only glycoprotein found. The proteins designated polypeptide 2 (MW 66 to 70,000) and nucleocapsid protein or NP (MW 61,000) were phosphorylated. The remaining virus-coded proteins were polypeptide 5 (MW 40,000) and the matrix or M protein (MW 37,000). Measles virions also contained a polypeptide (MW 42,000) thought to be actin due to co-migration with this component of uninfected cells. Analysis of in vitro 3 H-acetic anhydride radiolabeled virions confirmed the presence of these seven polypeptides. Acetic anhydride also labeled a protein designated polypeptide 4 (MW 53,000) which was not consistently radiolabeled in vivo, as well as several other minor proteins believed to be cellular in origin. Synthesis of the six virus-specific structural polypeptides was detected in lysates of infected cells by SDS-polyacrylamide slab gel electrophoresis. Virus specificity of polypeptide 4 could not be confirmed due to the similar MW of several cellular polypeptides. Two non-virion, but virus-specified polypeptides, of MW 38,000 and 18,000 were also detected. Synthesis of the virus structural proteins was in the same proportions as the polypeptides found in virions except for under production of polypeptide G and over production of polypeptide 2. (author)

  1. Cell-mediated immunity to herpes simplex in humans: lymphocyte cytotoxicity measured by 51Cr release from infected cells

    International Nuclear Information System (INIS)

    Russell, A.S.; Percy, J.S.; Kovithavongs, T.

    1975-01-01

    We assessed cell-mediated immunity to herpes simplex virus type 1 antigen in patients suffering from recurrent cold sores and in a series of healthy controls. Paradoxically, all those subject to recurrent herpetic infections had, without exception, evidence of cell-mediated immunity to herpes antigens. This was demonstrated by lymphocyte transformation and specific 51 Cr release from infected human amnion cells after incubation with peripheral blood mononuclear cells. Where performed, skin tests with herpes antigen were also positive. In addition, serum from these patients specifically sensitized herpes virus-infected cells to killing by nonimmune, control mononuclear cells. These tests were negative in the control patients except in a few cases, and it is suggested that these latter may be the asymptomatic herpes virus carriers previously recognized or that they may have experienced a genital infection. (U.S.)

  2. PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment

    Directory of Open Access Journals (Sweden)

    Frédéric Boal

    2016-02-01

    Full Text Available Shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. Here, we show that Shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (ICAM-1, a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme IpgD and its product, the lipid mediator PI5P. Overexpression of IpgD, but not a phosphatase dead mutant, induced the internalization and the degradation of ICAM-1 in intestinal epithelial cells. Remarkably, addition of permeant PI5P reproduced IpgD effects and led to the inhibition of neutrophil recruitment. Finally, these results were confirmed in an in vivo model of Shigella infection where IpgD-dependent ICAM-1 internalization reduced neutrophil adhesion. In conclusion, we describe here an immune evasion mechanism used by the pathogen Shigella to divert the host cell trafficking machinery in order to reduce immune cell recruitment.

  3. Urinary Tract Infection in Febrile Children with Sickle Cell Anaemia ...

    African Journals Online (AJOL)

    Eastern Nigeria. Children with this disease have increased tendency to develop frequent and severe infections especially of the urinary tract, bones and lungs. The prevalence of urinary tract infection (UTI) has however not been reported in this part ...

  4. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningi......Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...... a rapidly lethal, T cell-independent encephalitis, and infection resulted in a dramatic early up-regulation of chemokine gene expression. Similar marked up-regulation of chemokine expression was not seen until late after LCMV infection and required the presence of activated T cells. Cerebral CCR gene...... expression was dominated by CCR1, CCR2 and CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice, only LCMV-induced T cell-dependent inflammation was found to be associated with substantially increased expression of CCR genes. Virus-activated CD8+ T cells were found to express CCR2...

  5. Differences between Mycobacterium-Host Cell Relationships in Latent Tuberculous Infection of Mice Ex Vivo and Mycobacterial Infection of Mouse Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Elena Ufimtseva

    2016-01-01

    Full Text Available The search for factors that account for the reproduction and survival of mycobacteria, including vaccine strains, in host cells is the priority for studies on tuberculosis. A comparison of BCG-mycobacterial loads in granuloma cells obtained from bone marrow and spleens of mice with latent tuberculous infection and cells from mouse bone marrow and peritoneal macrophage cultures infected with the BCG vaccine in vitro has demonstrated that granuloma macrophages each normally contained a single BCG-Mycobacterium, while those acutely infected in vitro had increased mycobacterial loads and death rates. Mouse granuloma cells were observed to produce the IFNγ, IL-1α, GM-CSF, CD1d, CD25, CD31, СD35, and S100 proteins. None of these activation markers were found in mouse cell cultures infected in vitro or in intact macrophages. Lack of colocalization of lipoarabinomannan-labeled BCG-mycobacteria with the lysosomotropic LysoTracker dye in activated granuloma macrophages suggests that these macrophages were unable to destroy BCG-mycobacteria. However, activated mouse granuloma macrophages could control mycobacterial reproduction in cells both in vivo and in ex vivo culture. By contrast, a considerable increase in the number of BCG-mycobacteria was observed in mouse bone marrow and peritoneal macrophages after BCG infection in vitro, when no expression of the activation-related molecules was detected in these cells.

  6. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

    Directory of Open Access Journals (Sweden)

    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  7. A Role for Human Skin Mast Cells in Dengue Virus Infection and Systemic Spread.

    Science.gov (United States)

    Troupin, Andrea; Shirley, Devon; Londono-Renteria, Berlin; Watson, Alan M; McHale, Cody; Hall, Alex; Hartstone-Rose, Adam; Klimstra, William B; Gomez, Gregorio; Colpitts, Tonya M

    2016-12-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious global human disease and mortality. Skin immune cells are an important component of initial DENV infection and systemic spread. Here, we show that mast cells are a target of DENV in human skin and that DENV infection of skin mast cells induces degranulation and alters cytokine and growth factor expression profiles. Importantly, to our knowledge, we also demonstrate for the first time that DENV localizes within secretory granules in infected skin mast cells. In addition, DENV within extracellular granules was infectious in vitro and in vivo, trafficking through lymph to draining lymph nodes in mice. We demonstrate an important role for human skin mast cells in DENV infection and identify a novel mechanism for systemic spread of DENV infection from the initial peripheral mosquito injection site. Copyright © 2016 by The American Association of Immunologists, Inc.

  8. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  9. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    International Nuclear Information System (INIS)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang

    2014-01-01

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs

  10. A bovine cell line that can be infected by natural sheep scrapie prions.

    Directory of Open Access Journals (Sweden)

    Anja M Oelschlegel

    Full Text Available Cell culture systems represent a crucial part in basic prion research; yet, cell lines that are susceptible to prions, especially to field isolated prions that were not adapted to rodents, are very rare. The purpose of this study was to identify and characterize a cell line that was susceptible to ruminant-derived prions and to establish a stable prion infection within it. Based on species and tissue of origin as well as PrP expression rate, we pre-selected a total of 33 cell lines that were then challenged with natural and with mouse propagated BSE or scrapie inocula. Here, we report the successful infection of a non-transgenic bovine cell line, a sub-line of the bovine kidney cell line MDBK, with natural sheep scrapie prions. This cell line retained the scrapie infection for more than 200 passages. Selective cloning resulted in cell populations with increased accumulation of PrPres, although this treatment was not mandatory for retaining the infection. The infection remained stable, even under suboptimal culture conditions. The resulting infectivity of the cells was confirmed by mouse bioassay (Tgbov mice, Tgshp mice. We believe that PES cells used together with other prion permissive cell lines will prove a valuable tool for ongoing efforts to understand and defeat prions and prion diseases.

  11. Lymphocytes and macrophages are infected by Theileria equi, but T cells and B cells are not required to establish infection in vivo.

    Directory of Open Access Journals (Sweden)

    Joshua D Ramsay

    Full Text Available Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata, the intraleukocyte stage (schizont of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID, which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis

  12. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    Science.gov (United States)

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Operating characteristics of a partial-block randomized crossover bioequivalence study for dutasteride, a drug with a long half-life: investigation through simulation and comparison with final results.

    Science.gov (United States)

    Cai, Gengqian; Thiessen, Jake J; Baidoo, Charlotte A; Fossler, Michael J

    2010-10-01

    Studies to establish bioequivalence (BE) of a drug are important elements in support of drug applications. A typical BE study is conducted as a single dose, randomized, 2-period crossover design. For drugs with long half lives (≥ 48 hours) and evaluation of multiple BE objectives in 1 trial, this design may not be adequate. A parallel design may then be a more appropriate choice. However, parallel designs require increased sample size, which can become substantial. One option that is a compromise between the complete randomized block design and the parallel design is a partial-block crossover design. This approach came about during the development of a combination of dutasteride and tamsulosin. Previous experience with performing single-dose dutasteride studies suggested that 28 days of washout is needed between treatments because of its half-life of 7-9 days. Simulations were performed to assess the operating characteristics of this design using a previously developed PK model. Four scenarios were developed, and each scenario was simulated 500 times. The results showed that this design demonstrated acceptable consumer and producer risk. Partial-block crossover designs should be considered for studies when the half-life of the drug is long and there are more than 2 periods.

  14. Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

    Directory of Open Access Journals (Sweden)

    Haifeng C. Xu

    2017-11-01

    Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

  15. Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

    DEFF Research Database (Denmark)

    Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph

    2005-01-01

    Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

  16. Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability

    International Nuclear Information System (INIS)

    Rivera, Julie A.; McGuire, Travis C.

    2005-01-01

    To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV WSU5 infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected macrophages and DC stimulated similar levels of memory CTL responses in mixtures of CD8+ and CD4+ cells as detected with 51 Cr-release assays indicating that EIAV infection of DC did not alter antigen presentation. However, EIAV-infected DC were more effective than infected macrophages when used to stimulate memory CTL in isolated CD8+ cells. The maintenance of antigen processing and presenting function by EIAV-infected DC in vitro suggests that this function is maintained during in vivo infection

  17. Deficient CD4+ T cell priming and regression of CD8+ T cell functionality in virus-infected mice lacking a normal B cell compartment

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Kauffmann, Susanne Ørding; Thomsen, Allan Randrup

    2003-01-01

    of virus-specific CD4(+) T cells was markedly impaired in B(-/-) mice infected with either virus strain. Thus, our results indicate that B cells play an important role in antiviral immunity not only as Ab producers, but also in promoting an optimal and sustained T cell response. The T cell defects......In this study, we investigate the state of T cell-mediated immunity in B cell-deficient (B(-/-)) mice infected with two strains of lymphocytic choriomeningitis virus known to differ markedly in their capacity to persist. In B(-/-) C57BL mice infected with the more persisting virus, virus......-specific CD8(+) T cells are initially generated that are qualitatively similar to those in wild-type mice. However, although cell numbers are well sustained over time, the capacity to produce cytokines is rapidly impaired. In similarly infected B(-/-) BALB/c mice, virus-specific CD8(+) T cells are completely...

  18. Lipid Metabolism in Vascular Smooth Muscle Cells Infuenced by HCMV Infection

    Directory of Open Access Journals (Sweden)

    Lingfang Li

    2016-10-01

    Full Text Available Background: The present study was designed to observe the infection of human cytomegalovirus (HCMV to human vascular smooth muscle cells (VSMCs, and the effect of viral infection on lipid metabolism in VSMCs. Methods: The cytopathic effects were observed by inverted microscopy and viral infection were examined by electron microscopy and RT-PCR. The lipid metabolism related gene profiling of VSMCs after HCMV infection was assayed by cDNA assay and the abnormal expression of genes were validated by quantitative RT-PCR. The content of cholesterol in VSMCs after HCMV infection was assayed by cholesterol detection kit. Results: VSMCs showed obvious cytopathic effects after HCMV infection. Intact viral particles could be detected in VSMCs using electron microscope. By use of RT-PCR technology, IE gene of HCMV could be amplified from VSMCs. The expression of cell lipid metabolism related gene profiling showed obvious disorders. The expression levels of HMG-CoA synthase and HMG-CoA reductase after infection increased significantly. The cellular cholesterol content (µmol/106 cells was significantly higher than that of mock infected group at 72h post infection. Conclusion: HCMV can infect VSMCs and the infection can affect cellular lipid metabolism related gene expression, which get involved in the occurrence and development of atherosclerosis (AS.

  19. EBV infection is common in gingival epithelial cells of the periodontium and worsens during chronic periodontitis.

    Directory of Open Access Journals (Sweden)

    Séverine Vincent-Bugnas

    Full Text Available An amplifying role for oral epithelial cells (ECs in Epstein-Barr Virus (EBV infection has been postulated to explain oral viral shedding. However, while lytic or latent EBV infections of oro/nasopharyngeal ECs are commonly detected under pathological conditions, detection of EBV-infected ECs in healthy conditions is very rare. In this study, a simple non-surgical tissue sampling procedure was used to investigate EBV infection in the periodontal epithelium that surrounds and attaches teeth to the gingiva. Surprisingly, we observed that the gingival ECs of the periodontium (pECs are commonly infected with EBV and may serve as an important oral reservoir of latently EBV-infected cells. We also found that the basal level of epithelial EBV-infection is significantly increased in chronic periodontitis, a common inflammatory disease that undermines the integrity of tooth-supporting tissues. Moreover, the level of EBV infection was found to correlate with disease severity. In inflamed tissues, EBV-infected pECs appear to be prone to apoptosis and to produce larger amounts of CCL20, a pivotal inflammatory chemokine that controls tissue infiltration by immune cells. Our discovery that the periodontal epithelium is a major site of latent EBV infection sheds a new light on EBV persistence in healthy carriers and on the role of this ubiquitous virus in periodontitis. Moreover, the identification of this easily accessible site of latent infection may encourage new approaches to investigate and monitor other EBV-associated disorders.

  20. Polyploidization on SK-N-MC human neuroblastoma cells infected with herpes simplex virus 1.

    Science.gov (United States)

    Karalyan, Zaven; Izmailyan, Roza; Karalova, Elena; Abroyan, Liana; Hakobyan, Lina; Avetisyan, Aida; Semerjyan, Zara

    2016-01-01

    Polyploidization is one of the most dramatic changes occurring within cell genome owing to various reasons including under many viral infections. We examined the impact of herpes simplex virus-1 (HSV-1) on SK-N-MC human neuroblastoma cell line. The infected cells were followed from 6 hours up to 96 hours post infection (hpi). A large number of polyploid cells with giant nuclei was observed under the influence of HSV-1 at 24 hpi with the DNA content of 32c to 64c or more, in comparison with control SK-N-MC cells that were characterized by relatively moderate values of ploidy, i.e. 8с to 16с (where 1c is the haploid amount of nuclear DNA found in normal diploid populations in G0/G1). After 48-96 hpi, the population of polyploid cells with giant nuclei decreased to the benchmark level. The SK-NMC cells infected with HSV-1 for 24 hours were stained with gallocyanine and monitored for cytological features. The infected cells underwent virus induced cellcell and nuclei fusion with the formation of dense nuclei syncytium. The metabolic activity of HSV-1 infected cells was higher in both nuclei and nucleoli when compared to control cells.

  1. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers.

    Science.gov (United States)

    Fukazawa, Yoshinori; Lum, Richard; Okoye, Afam A; Park, Haesun; Matsuda, Kenta; Bae, Jin Young; Hagen, Shoko I; Shoemaker, Rebecca; Deleage, Claire; Lucero, Carissa; Morcock, David; Swanson, Tonya; Legasse, Alfred W; Axthelm, Michael K; Hesselgesser, Joseph; Geleziunas, Romas; Hirsch, Vanessa M; Edlefsen, Paul T; Piatak, Michael; Estes, Jacob D; Lifson, Jeffrey D; Picker, Louis J

    2015-02-01

    Chronic-phase HIV and simian immunodeficiency virus (SIV) replication is reduced by as much as 10,000-fold in elite controllers (ECs) compared with typical progressors (TPs), but sufficient viral replication persists in EC tissues to allow viral sequence evolution and induce excess immune activation. Here we show that productive SIV infection in rhesus monkey ECs, but not TPs, is markedly restricted to CD4(+) follicular helper T (TFH) cells, suggesting that these EC monkeys' highly effective SIV-specific CD8(+) T cells can effectively clear productive SIV infection from extrafollicular sites, but their relative exclusion from B cell follicles prevents their elimination of productively infected TFH cells. CD8(+) lymphocyte depletion in EC monkeys resulted in a dramatic re-distribution of productive SIV infection to non-TFH cells, with restriction of productive infection to TFH cells resuming upon CD8(+) T cell recovery. Thus, B cell follicles constitute 'sanctuaries' for persistent SIV replication in the presence of potent anti-viral CD8(+) T cell responses, potentially complicating efforts to cure HIV infection with therapeutic vaccination or T cell immunotherapy.

  2. Impact of HPV infection on oral squamous cell carcinoma.

    Science.gov (United States)

    Götz, Carolin; Drecoll, Enken; Straub, Melanie; Bissinger, Oliver; Wolff, Klaus-Dietrich; Kolk, Andreas

    2016-11-22

    Head and neck squamous cell carcinomas (HNSCC) are often divided by their aetiology. Noxae associated collectives are compared with the human papilloma virus (HPV)-associated group, whereas different localisations of oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas are mostly discussed as one single group. Our aim was to show that classification by aetiology is not appropriate for OSCC. HPV DNA was detected by PCR in 7 (3.47%) patients, and we identified 12 (5.94%) positive (+) cases by p16INK4a immunostaining. Only 4 (1.98%) of the p16INK4a+ cases were + for HPV using PCR. Our homogenous collective of OSCC allowed us to compare HPV+ and HPV negative (-) patients without creating bias for tumour localisation, age, gender or tumour stage. After testing OSCC samples for HPV positivity, we compared the results of two commonly used HPV detection methods, p16INK4a immunostaining and HPV DNA-related PCR, on 202 OSCC patients. HPV subtypes were determined with an HPV LCD Array Kit. Clinicopathological features of the patients were analysed, and the disease specific survival rates (DSS) for HPV+ and HPV- patients were obtained. p16INK4a immunostaining is a not a reliable HPV detection method for OSCC. Positive p16INK4a immunostaining did not agree with + results from PCR of HPV DNA. Furthermore, the influence of HPV-related oncogenic transformation in OSCC is overestimated. The significance of HPV infection remains clinically unclear, and its influence on survival rates is not relevant to OSCC cases.

  3. EBI3 regulates the NK cell response to mouse cytomegalovirus infection

    DEFF Research Database (Denmark)

    Jensen, Helle; Chen, Shih-Yu; Folkersen, Lasse Westergaard

    2017-01-01

    Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induc......Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection....... The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3-/-) C57BL/6 (B6) mice during MCMV infection. Furthermore, comparable levels of early viral...... replication in spleen and liver were observed in MCMV-infected Ebi3-/- and wild-type (WT) B6 mice. Interestingly, the viral load in salivary glands and oral lavage was strongly decreased in the MCMV-infected Ebi3-/- B6 mice, suggesting that EBI3 plays a role in the establishment of MCMV latency. We detected...

  4. Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells.

    Science.gov (United States)

    Alugubelly, Navatha; Hercik, Kamil; Kibler, Peter; Nanduri, Bindu; Edelmann, Mariola J

    2016-05-01

    Yersinia enterocolitica is a facultative intracellular pathogen and a causative agent of yersiniosis, which can be contracted by ingestion of contaminated food. Yersinia secretes virulence factors to subvert critical pathways in the host cell. In this study we utilized shotgun label-free proteomics to study differential protein expression in epithelial cells infected with Y.enterocolitica. We identified a total of 551 proteins, amongst which 42 were downregulated (including Prostaglandin E Synthase 3, POH-1 and Karyopherin alpha) and 22 were upregulated (including Rab1 and RhoA) in infected cells. We validated some of these results by western blot analysis of proteins extracted from Caco-2 and HeLa cells. The proteomic dataset was used to identify host canonical pathways and molecular functions modulated by this infection in the host cells. This study constitutes a proteome of Yersinia-infected cells and can support new discoveries in the area of host-pathogen interactions. We describe a proteome of Yersinia enterocolitica-infected HeLa cells, including a description of specific proteins differentially expressed upon infection, molecular functions as well as pathways altered during infection. This proteomic study can lead to a better understanding of Y. enterocolitica pathogenesis in human epithelial cells. Copyright © 2016. Published by Elsevier B.V.

  5. Flow cytometric monitoring of influenza A virus infection in MDCK cells during vaccine production

    Directory of Open Access Journals (Sweden)

    Reichl Udo

    2008-04-01

    Full Text Available Abstract Background In cell culture-based influenza vaccine production the monitoring of virus titres and cell physiology during infection is of great importance for process characterisation and optimisation. While conventional virus quantification methods give only virus titres in the culture broth, data obtained by fluorescence labelling of intracellular virus proteins provide additional information on infection dynamics. Flow cytometry represents a valuable tool to investigate the influences of cultivation conditions and process variations on virus replication and virus yields. Results In this study, fluorescein-labelled monoclonal antibodies against influenza A virus matrix protein 1 and nucleoprotein were used for monitoring the infection status of adherent Madin-Darby canine kidney cells from bioreactor samples. Monoclonal antibody binding was shown for influenza A virus strains of different subtypes (H1N1, H1N2, H3N8 and host specificity (human, equine, swine. At high multiplicity of infection in a bioreactor, the onset of viral protein accumulation in adherent cells on microcarriers was detected at about 2 to 4 h post infection by flow cytometry. In contrast, a significant increase in titre by hemagglutination assay was detected at the earliest 4 to 6 h post infection. Conclusion It is shown that flow cytometry is a sensitive and robust method for the monitoring of viral infection in fixed cells from bioreactor samples. Therefore, it is a valuable addition to other detection methods of influenza virus infection such as immunotitration and RNA hybridisation. Thousands of individual cells are measured per sample. Thus, the presented method is believed to be quite independent of the concentration of infected cells (multiplicity of infection and total cell concentration in bioreactors. This allows to perform detailed studies on factors relevant for optimization of virus yields in cell cultures. The method could also be used for process

  6. HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

    Science.gov (United States)

    Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

    2017-12-01

    The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

  7. Lipofectamine and related cationic lipids strongly improve adenoviral infection efficiency of primitive human hematopoietic cells.

    Science.gov (United States)

    Byk, T; Haddada, H; Vainchenker, W; Louache, F

    1998-11-20

    Adenoviral vectors have the potential to infect a large number of cell types including quiescent cells. Their use in hematopoietic cells is limited by the episomal form of their DNA, leading to transgene loss in the progeny cells. However, the use of this vector may be interesting for short-term in vitro modifications of primitive human hematopoietic cells. Therefore, we have investigated the ability of adenovirus to transduce cord blood CD34+ cells. Several promoters were tested using the lacZ reporter gene. The PGK and CMV promoters induced transgene expression in 18-25% of the cells, whereas the HTLV-I and especially the RSV promoter were almost inactive. To improve infection efficiency, adenovirus was complexed with cationic lipids. Lipofectamine, Cellfectin, and RPR120535b, but not Lipofectin, Lipofectace, or DOTAP, markedly improved transgene expression in CD34+ cells (from 19 to 35%). Lipofectamine strongly enhanced infection efficiency of the poorly infectable primitive CD34+CD38low cells (from 11 to 28%) whereas the more mature CD34+CD38+ cells were only slightly affected (from 24 to 31%). Lipofectamine tripled the infection of CFU-GMs and LTC-ICs derived from the CD34+CD38low cell fraction (from 4 to 12% and from 5 to 16%, respectively) and doubled that of BFU-Es (from 13 to 26%). We conclude that cationic lipids can markedly increase the efficiency of adenovirus-mediated gene transfer into primitive hematopoietic cells.

  8. Infection of Human Fallopian Tube Epithelial Cells with Neisseria gonorrhoeae Protects Cells from Tumor Necrosis Factor Alpha-Induced Apoptosis

    Science.gov (United States)

    Morales, Priscilla; Reyes, Paz; Vargas, Macarena; Rios, Miguel; Imarai, Mónica; Cardenas, Hugo; Croxatto, Horacio; Orihuela, Pedro; Vargas, Renato; Fuhrer, Juan; Heckels, John E.; Christodoulides, Myron; Velasquez, Luis

    2006-01-01

    Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-α). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-α was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-α antibodies; and (iii) the addition of exogenous TNF-α induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-α-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-α-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease. PMID:16714596

  9. Block effect on HCV infection by HMGB1 released from virus-infected cells: An insight from mathematical modeling

    Science.gov (United States)

    Wang, Wei; Ma, Wanbiao

    2018-06-01

    The nuclear protein high-mobility group box 1 (HMGB1) can have an active role in deoxyribonucleic acid (DNA) organization and the regulation of transcription. Based on the new findings from a recent experimental study, the blocking effect on HCV infection by HMGB1 released from virus-infected cells is investigated using a diffusive model for viral infection dynamics. In the model, the diffusion of the virus depends not only on its concentration gradient, but also on the concentration of HMGB1. The basic reproduction number, threshold dynamics, stability properties of the steady states, travelling wave solutions, and spreading speed for the proposed model are studied. We show that the HMGB1-induced blocking of HCV infection slows the spread of virus compared with random diffusion only. Numerically, it is shown that a high concentration of HMGB1 can block the spread of virus and this confirms, not only qualitatively but also quantitatively, the experimental result.

  10. Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells

    Energy Technology Data Exchange (ETDEWEB)

    Cong, Yingying; Li, Xiaoxue; Bai, Yunyun [College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 (China); Lv, Xiaonan [College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 (China); CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100090 (China); Herrler, Georg [Institute for Virology, University of Veterinary Medicine, Hannover D-30559 (Germany); Enjuanes, Luis [Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Cantoblanco, Madrid (Spain); Zhou, Xingdong [College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 (China); Qu, Bo [Faculty of Life Sciences, Northeast Agricultural University, Harbin 150030 (China); Meng, Fandan [Institute for Virology, University of Veterinary Medicine, Hannover D-30559 (Germany); Cong, Chengcheng [College Animal Husbandry and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110161 (China); Ren, Xiaofeng; Li, Guangxing [College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030 (China)

    2015-04-15

    Infection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells. - Highlights: • PEDV infection of polarized intestinal epithelial cells (IECs) was characterized. • Porcine aminpeptidase N (pAPN) facilitated PEDV infection in IECs. • PEDV entry into and release from polarized cell via its apical membrane. • PEDV infection may proceed by lateral spread of virus in IECs.

  11. Porcine aminopeptidase N mediated polarized infection by porcine epidemic diarrhea virus in target cells

    International Nuclear Information System (INIS)

    Cong, Yingying; Li, Xiaoxue; Bai, Yunyun; Lv, Xiaonan; Herrler, Georg; Enjuanes, Luis; Zhou, Xingdong; Qu, Bo; Meng, Fandan; Cong, Chengcheng; Ren, Xiaofeng; Li, Guangxing

    2015-01-01

    Infection of polarized intestinal epithelial cells by porcine epidemic diarrhea virus (PEDV) was characterized. Indirect immunofluorescence assay, real-time PCR, and transmission electron microscopy confirmed PEDV can be successfully propagated in immortalized swine small intestine epithelial cells (IECs). Infection involved porcine aminpeptidase N (pAPN), a reported cellular receptor for PEDV, transient expression of pAPN and siRNA targeted pAPN increased and decreased the infectivity of PEDV in IECs, respectively. Subsequently, polarized entry into and release from both Vero E6 and IECs was analyzed. PEDV entry into polarized cells and pAPN grown on membrane inserts occurs via apical membrane. The progeny virus released into the medium was also quantified which demonstrated that PEDV is preferentially released from the apical membrane. Collectively, our data demonstrate that pAPN, the cellular receptor for PEDV, mediates polarized PEDV infection. These results imply the possibility that PEDV infection may proceed by lateral spread of virus in intestinal epithelial cells. - Highlights: • PEDV infection of polarized intestinal epithelial cells (IECs) was characterized. • Porcine aminpeptidase N (pAPN) facilitated PEDV infection in IECs. • PEDV entry into and release from polarized cell via its apical membrane. • PEDV infection may proceed by lateral spread of virus in IECs

  12. Legionella pneumophila infection of Drosophila S2 cells induces only minor changes in mitochondrial dynamics.

    Directory of Open Access Journals (Sweden)

    Elizabeth Wen Sun

    Full Text Available During infection of cells by Legionella pneumophila, the bacterium secretes a large number of effector proteins into the host cell cytoplasm, allowing it to alter many cellular processes and make the vacuole and the host cell into more hospitable environments for bacterial replication. One major change induced by infection is the recruitment of ER-derived vesicles to the surface of the vacuole, where they fuse with the vacuole membrane and prevent it from becoming an acidified, degradative compartment. However, the recruitment of mitochondria to the region of the vacuole has also been suggested by ultrastructural studies. In order to test this idea in a controlled and quantitative experimental system, and to lay the groundwork for a genome-wide screen for factors involved in mitochondrial recruitment, we examined the behavior of mitochondria during the early stages of Legionella pneumophila infection of Drosophila S2 cells. We found that the density of mitochondria near vacuoles formed by infection with wild type Legionella was not different from that found in dotA(- mutant-infected cells during the first 4 hours after infection. We then examined 4 parameters of mitochondrial motility in infected cells: velocity of movement, duty cycle of movement, directional persistence and net direction. In the 4 hours following infection, most of these measures were indistinguishable between wild type and dotA(-.infection. However, wild type Legionella did induce a modest shift in the velocity distribution toward faster movement compared dotA(- infection, and a small downward shift in the duty cycle distribution. In addition, wild type infection produced mitochondrial movement that was biased in the direction of the bacterial vacuole relative to dotA-, although not enough to cause a significant accumulation within 10 um of the vacuole. We conclude that in this host cell, mitochondria are not strongly recruited to the vacuole, nor is their motility

  13. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Science.gov (United States)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  14. Diagnosis of arterial prosthetic graft infection by 111In oxine white blood cell scans

    International Nuclear Information System (INIS)

    McKeown, P.P.; Miller, D.C.; Jamieson, S.W.; Mitchell, R.S.; Reitz, B.A.; Olcott, C.; Mehigan, J.T.; Silberstein, R.J.; McDougall, I.R.

    1982-01-01

    Early and accurate diagnosis of infected prosthetic arterial grafts is difficult, despite the application of diverse diagnostic modalities. Delay in making the diagnosis is largely responsible for the high amputation and mortality rates associated with this complication. In nine patients with suspected graft infections, 111 In white blood cell scanning was useful and accurate. Graft infection was proved in five cases and ruled out in three. One false-positive scan was due to a sigmoid diverticular abscess overlying the graft. 111 In white blood cell scans may improve the accuracy of diagnosing infected prosthetic grafts, which may result in better limb and patient salvage rates

  15. Vaccination with experimental feline immunodeficiency virus vaccines, based on autologous infected cells, elicits enhancement of homologous challenge infection

    NARCIS (Netherlands)

    J.A. Karlas (Jos); C.H.J. Siebelink (Kees); M.A. Peer; W. Huisman (Willem); A.M. Cuisinier; G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractCats were vaccinated with fixed autologous feline immunodeficiency virus (FIV)-infected cells in order to present viral proteins to the immune system of individual cats in an MHC-matched fashion. Upon vaccination, a humoral response against Gag was induced. Furthermore,

  16. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

    Science.gov (United States)

    Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

  17. Chronic schistosomiasis during pregnancy epigenetically reprograms T-cell differentiation in offspring of infected mothers.

    Science.gov (United States)

    Klar, Kathrin; Perchermeier, Sophie; Bhattacharjee, Sonakshi; Harb, Hani; Adler, Thure; Istvanffy, Rouzanna; Loffredo-Verde, Eva; Oostendorp, Robert A; Renz, Harald; Prazeres da Costa, Clarissa

    2017-05-01

    Schistosomiasis is a nontransplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B-cell and T-cell development. Therefore, we focused our analyses on T-cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here, we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into T H 1 cells, whereas T H 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in naïve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the naïve T-cell compartment affecting T H 2 and T H 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T-cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection