Two different mutations in the envelope protein of feline immunodeficiency virus allow the virus to escape from neutralization by feline serum antibodies.

NARCIS (Netherlands)

C.H.J. Siebelink (Kees); M.L. Bosch (Marnix); G.F. Rimmelzwaan (Guus); R.H. Meloen; A.D.M.E. Osterhaus (Albert)

1995-01-01

textabstractViral progeny of two molecular clones of feline immunodeficiency virus (FIV), 19k1 and 19k32, were tested in a virus neutralization assay. In this assay the infection of thymocytes with FIV19k1 was neutralized by serum S1422, derived from an SPF cat 22 weeks after infection with FIV19k1.

The comparison between the humoral response and the neutralizing capacity of sheep serum inoculated with natural venom and Co60 irradiated venom from Crotalus durissus terrificus (Laurenti, 1768)

International Nuclear Information System (INIS)

Netto, D.P.

2000-01-01

Crotalus durissus terrificus venom was irradiated with Co 60 to investigate the effects of antigen-irradiation on antivenom production in sheep. Twelve sheep were divided in two groups of 6. One group received irradiated, while the other received natural venom. Three doses of antigen were given at monthly intervals. The toxic activity of the venom was assessed by LD 50 in mice. Weekly blood samples were obtained to evaluate anti-crotalic serum titers by indirect ELISA, neutralization capacity, and serum potency. A complete blood count, plasma protein and fibrinogen concentration, and serum albumin and globulin were also determined. At end of the experiment, the animals were challenged with ovine LD 50 , without clinical abnormalities. (author)

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN epitopes

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Sunil R Vaidya

2016-01-01

Full Text Available Background & objectives: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. Methods: By using commercial mumps IgG enzyme immunoassay (EIA and a rapid focus reduction neutralization test (FRNT, a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G and Leningrad-Zagreb vaccine strain (genotype N were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. Results: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05. The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Interpretation & conclusions:Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

Cross-neutralization between three mumps viruses & mapping of haemagglutinin-neuraminidase (HN) epitopes.

Science.gov (United States)

Vaidya, Sunil R; Dvivedi, Garima M; Jadhav, Santoshkumar M

2016-01-01

The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross-neutralization activity of Indian mumps viruses. By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates.

The comparison between the humoral response and the neutralizing capacity of sheep serum inoculated with natural venom and Co{sup 60} irradiated venom from Crotalus durissus terrificus (Laurenti, 1768)

Energy Technology Data Exchange (ETDEWEB)

Netto, D.P. [Universidade Estadual de Londrina, PR (Brazil). Centro de Ciencias Agrarias. Dept. de Medicina Veterinaria Preventiva]. E-mail: mnetto@uel.br

2000-07-01

Crotalus durissus terrificus venom was irradiated with Co{sup 60} to investigate the effects of antigen-irradiation on antivenom production in sheep. Twelve sheep were divided in two groups of 6. One group received irradiated, while the other received natural venom. Three doses of antigen were given at monthly intervals. The toxic activity of the venom was assessed by LD{sub 50} in mice. Weekly blood samples were obtained to evaluate anti-crotalic serum titers by indirect ELISA, neutralization capacity, and serum potency. A complete blood count, plasma protein and fibrinogen concentration, and serum albumin and globulin were also determined. At end of the experiment, the animals were challenged with ovine LD{sub 50}, without clinical abnormalities. (author)

SERUM PARAOXONASE ACTIVITY IN RENAL TRANSPLANT RECIPIENTS

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Saritha Gadicherla

2017-12-01

Full Text Available BACKGROUND Serum paraoxonase is an enzyme synthesised in the liver. It is known to prevent atherosclerosis by inhibiting oxidation of lowdensity lipoprotein. Renal transplant recipients have increased tendency for developing atherosclerosis and cardiovascular disease. Reduced activity of serum paraoxonase contributes to accelerated atherosclerosis and increased cardiovascular complications in these patients. The aim of this study was to estimate serum paraoxonase activity in renal transplant recipients and compare it with healthy controls. MATERIALS AND METHODS 30 renal transplant recipients and 30 age and sex matched healthy controls were taken for the study. Serum paraoxonase activity, blood urea, serum creatinine and uric acid were estimated in these groups. The serum paraoxonase activity was correlated with urea, creatinine and uric acid levels. RESULTS Serum paraoxonase activity was reduced in renal transplant recipients compared to healthy controls. There was a negative correlation between paraoxonase activity and the levels of urea, creatinine and uric acid levels. CONCLUSION In this study, the paraoxonase activity was reduced in renal transplant recipients compared to controls. The increased cardiovascular disease in these patients could be due to reduced paraoxonase activity.

Electric-current Neutralization, Magnetic Shear, and Eruptive Activity in Solar Active Regions

Energy Technology Data Exchange (ETDEWEB)

Liu, Yang; Sun, Xudong [W. W. Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA 94305-4085 (United States); Török, Tibor; Titov, Viacheslav S. [Predictive Science Inc., 9990 Mesa Rim Road, Suite 170, San Diego, CA 92121 (United States); Leake, James E. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

2017-09-01

The physical conditions that determine whether or not solar active regions (ARs) produce strong flares and coronal mass ejections (CMEs) are not yet well understood. Here, we investigate the association between electric-current neutralization, magnetic shear along polarity inversion lines (PILs), and eruptive activity in four ARs: two emerging and two well-developed ones. We find that the CME-producing ARs are characterized by a strongly non-neutralized total current, while the total current in the ARs that did not produce CMEs is almost perfectly neutralized. The difference in the PIL shear between these two groups is much less pronounced, which suggests that the degree of current neutralization may serve as a better proxy for assessing the ability of ARs to produce CMEs.

Active ion temperature measurement with heating neutral beam

International Nuclear Information System (INIS)

Miura, Yukitoshi; Matsuda, Toshiaki; Yamamoto, Shin

1987-03-01

When the heating neutral-beam (hydrogen beam) is injected into a deuterium plasma, the density of neutral particles is increased locally. By using this increased neutral particles, the local ion temperature is measured by the active charge-exchange method. The analyzer is the E//B type mass-separated neutral particle energy analyzer and the measured position is about one third outside of the plasma radius. The deuterium energy spectrum is Maxwellian, and the temperature is increased from 350 eV to 900 eV during heating. Since the local hydrogen to deuterium density concentration and the density of the heating neutral-beam as well as the ion temperature can be obtained good S/N ratio, the usefulness of this method during neutral-beam heating is confirmed by this experiment. (author)

Use of 51Cr release to measure the cytotoxic effects of staphylococcal leukocidin and toxin neutralization on bovine leukocytes

International Nuclear Information System (INIS)

Loeffler, D.A.; Schat, K.A.; Norcross, N.L.

1986-01-01

Leukocidin toxin from Staphylococcus aureus produces specific cytolytic effects on neutrophils and macrophages. The most commonly used method for determination of leukocidin activity is microscopic examination for characteristic morphological changes in toxin-treated cells. The 51 Cr release assay was modified to allow quantitation of the cytolytic effects of leukocidin on bovine peripheral blood neutrophils and lymphocytes. Toxin neutralization by serum and milk samples was quantitated by this method. The neutralizing abilities of the various samples were found to correlate with the levels of immunoglobulin G (IgG1) specific for leukocidin. Undiluted normal serum samples, however, were capable of partially preventing the cytotoxic effects of leukocidin. The assay was shown to be an effective means of quantitating the cytotoxic activity of leukocidin on neutrophils as well as demonstrating neutralization of cytotoxicity by milk and serum samples

Ternary mixed-mode silica sorbent of solid-phase extraction for determination of basic, neutral and acidic drugs in human serum.

Science.gov (United States)

Jin, Shupei; Qiao, Yinghua; Xing, Jun

2018-06-01

In this study, a ternary mixed-mode silica sorbent (TMSS) with octamethylene, carboxyl, and amino groups was prepared via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction and a subsequent reduction of azide to primary amine. While used in solid-phase extraction (SPE), the retention behavior of TMSS towards a total of nine kinds of basic, neutral, and acidic drugs was investigated in detail. The results revealed that hydrophobic, ion-exchange interaction, and electrostatic repulsion between TMSS and the analytes were closely related to the retention behavior of TMSS. Besides, the log K ow value of the analyte was also a factor influencing the retention behavior of analytes on TMSS. The nine analytes could be retained by TMSS simultaneously and then, were eluted into two fractions according to the acid-base property of the analytes for further determinations. The acidic and neutral analytes were in one fraction, and the basic ones in the other fraction. When used to treat the human serum spiked with the nine drugs, TMSS offered higher recoveries than BakerBond CBA and comparable recoveries to Oasis WCX. It should be noted TMSS had better purifying capability for human serum than Oasis WCX. Under the optimized SPE conditions, a method of SPE hyphenated to high-performance liquid chromatography-ultraviolet detection (HPLC-UV) for determination of the basic, neutral, and acidic drugs spiked in human serum was established. For the nine drugs, the linear ranges were all between 5.0 and 1000 μg L -1 with correlation coefficients (R 2 ) above 0.9990, and the limits of detection (LODs) were in the range of 0.8-2.3 μg L -1 . The intra-day and inter-day relative standard deviations (RSDs) were less than 5.3 and 8.8%, respectively. Graphical abstract Treating drugs in human serum by SPE with ternary mixed-mode silica sorbent.

Active neutral particle diagnostics for high temperature plasma

International Nuclear Information System (INIS)

Tobita, Kenji

1993-01-01

This paper describes experimental studies related to active neutral particle diagnostics in the JT-60 tokamak. Detection efficiencies of a micro-channel plate (MCP), which has widely used in plasma diagnostics, were determined for ions and neutrals. Multi-step processes for a neutral beam is predicted to enhance the beam stopping cross section in a plasma. In order to confirm the predictions, shine-through for a hydrogen and for a helium beam was measured in the JT-60 ohmic plasmas. The measurements for a hydrogen beam resulted in the cross sectional enhancement in the beam stopping. The same experiment using a helium beam indicated that the cross sectional enhancement for helium was much smaller than that for hydrogen at almost same plasma parameters. Ion temperature diagnostic using active beam scattering was developed in data processing technique, in consideration of the device function of a neutral particle analyzer and in estimation of the effect of beam ion component. Fundamental experiments for detecting helium ions in a plasma were performed using two-electron transfer reaction between a helium atomic beam and helium ions, and the energy distribution and the density of the helium ions were determined. These experiments demonstrated promise of the two-electron transfer reaction as an alpha ash detection in a burning plasma. A parasitic neutral efflux accompanied by active beam injection was investigated. (J.P.N.)

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.

Science.gov (United States)

Malerczyk, Claudius; Freuling, Conrad; Gniel, Dieter; Giesen, Alexandra; Selhorst, Thomas; Müller, Thomas

2014-01-01

Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2. Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV. Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate). Cross-neutralizing activities partly correlate with the

Myostatin inhibitors in sports drug testing: Detection of myostatin-neutralizing antibodies in plasma/serum by affinity purification and Western blotting.

Science.gov (United States)

Walpurgis, Katja; Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

2016-02-01

Myostatin is a key regulator of skeletal muscle growth and inhibition of its signaling pathway results in an increased muscle mass and function. The aim of this study was to develop a qualitative detection assay for myostatin-neutralizing antibodies for doping control purposes by using immunological approaches. To detect different types of myostatin-neutralizing antibodies irrespective of their amino acid sequence, an immunological assay specific for antibodies directed against myostatin and having a human Fc domain was established. Affinity purification and Western blotting strategies were combined to allow extracting and identifying relevant analytes from 200 μL of plasma/serum in a non-targeted approach. The assay was characterized regarding specificity, linearity, precision, robustness, and recovery. The assay was found to be highly specific, robust, and linear from 0.1 to 1 μg/mL. The precision was successfully specified at three different concentrations and the recovery of the affinity purification was 58%. Within this study, an immunological detection assay for myostatin-neutralizing antibodies present in plasma/serum specimens was developed and successfully characterized. The presented approach can easily be modified to include other therapeutic antibodies and serves as proof-of-concept for the detection of antibody-based myostatin inhibitors in doping control samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mucorales species activation of a serum leukotactic factor.

Science.gov (United States)

Marx, R S; Forsyth, K R; Hentz, S K

1982-01-01

Previous studies have suggested that the focal accumulation of phagocytic leukocytes is an important feature of the host response in mucormycosis. To ascertain the basis for this influx of inflammatory cells, we evaluated the effect of members of the order Mucorales, including species from the genera Rhizopus, Absidia, and Mucor, on the chemotactic activity of normal human serum for neutrophils and monocytes. Both hyphae and spores produced concentration-dependent chemotaxigenesis in serum to a maximum level equivalent to that produced by zymosan activation of serum. Chemotactic activity was similar for live and heat-killed hyphae. No leukotactic activity was demonstrated in the absence of serum. The pretreatment of serum with anti-C3 antibody, heating at 56 degrees C, or 0.01 M EDTA abolished the activity. The pretreatment of serum with 0.01 M ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid did not abolish the activity. These data provide evidence that the leukotactic activity of Mucorales species is generated through the alternative complement pathway. PMID:6759409

Serum neutralization as a differential serological test for classical swine fever virus and other pestivirus infections

Directory of Open Access Journals (Sweden)

Paredes J.C.M.

1999-01-01

Full Text Available Serum neutralization tests (SN were performed against classical swine fever virus (CSFV, bovine viral diarrhea virus (BVDV and border disease virus (BDV on samples of swine serum collected for screening of antibodies to CSFV, in order to determine the SN value as a differential serological test. Ninety-nine sera out of a sample of 16,664 were positive for antibodies to pestiviruses in an ELISA test which did not distinguish antibodies to different pestiviruses. When submitted to SN, 81 sera were positive for CSFV antibodies only. In 17 sera, crossreactive antibodies to either CSFV, BVDV or BDV were detected. In most of these sera (13 out of 17 the differences between SN titres against the three viruses were not sufficient to estimate which was the most likely antibody-inducing virus. It was concluded that, for the SN to be useful in such differentiation, it is essential to examine a sample which must include a representative number of sera from the same farm where suspect animals were detected. When isolated serum samples are examined, such as those obtained with the sampling strategy adopted here, the SN may give rise to inconclusive results.

[Virus strain specific serum neutralizing antibodies in children and adolescents immunized with a Russian mumps vaccine].

Science.gov (United States)

Otrashevskaia, E V; Krasil'nikov, I V; Ignat'ev, G M

2010-01-01

Postvaccination immunity was studied in the children and teenagers without a history of clinical mumps infection, who had been immunized with the Leningrad-3 mumps vaccine. The level of specific lgG in ELISA and that and spectrum of their neutralizing activity against a vaccine strain and three heterologous mumps virus (MV) strains (genotypes A, C, and H) were measured. The investigation included 151 sera from the vaccinees aged 3 to 17 years, possessing the detectable specific IgG titers in ELISA and the detectable neutralizing titers against the vaccine strain. 97.4% of the vaccinees had neutralizing activity against 1-3 heterologous MV strains. A preponderance of neutralizing titers against heterologous MV strains by 1-log2 in some sera (6.5-32.5 depending on age) was most likely to suggest that the vaccinees' had been in contact with these virus strains in the past. In our investigation, a combination of positive IgG titers and neutralizing titers against the vaccine strain 2-log2 or higher provided the protection of the vaccinated children and teenagers against the symptomatic infection. There was a pronounced buster effect of the second immunization and a drop in the neutralizing activity of the sera from the vaccinated children and adolescents over time after the first and second immunization.

Serum paraoxonase 1 activity in dogs

DEFF Research Database (Denmark)

Rossi, Gabriele; Giordano, Alessia; Pezzia, Francesca

2013-01-01

Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs.......Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs....

Validation of a serum neutralization test for detection of antibodies specific to cyprinid herpesvirus 3 in infected common and koi carp (Cyprinus carpio).

Science.gov (United States)

Cabon, J; Louboutin, L; Castric, J; Bergmann, S; Bovo, G; Matras, M; Haenen, O; Olesen, N J; Morin, T

2017-05-01

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a serious infective, notifiable disease affecting common carp and varieties. In survivors, infection is generally characterized by a subclinical latency phase with restricted viral replication. The CyHV-3 genome is difficult to detect in such carrier fish that represent a potential source of dissemination if viral reactivation occurs. In this study, the analytical and diagnostic performance of an alternative serum neutralization (SN) method based on the detection of CyHV-3-specific antibodies was assessed using 151 serum or plasma samples from healthy and naturally or experimentally CyHV-3-infected carp. French CyHV-3 isolate 07/108b was neutralized efficiently by sera from carp infected with European, American and Taiwanese CyHV-3 isolates, but no neutralization was observed using sera specific to other aquatic herpesviruses. Diagnostic sensitivity, diagnostic specificity and repeatability of 95.9%, 99.0% and 99.3%, respectively, were obtained, as well as a compliance rate of 89.9% in reproducibility testing. Neutralizing antibodies were steadily detected in infected carp subjected to restrictive or permissive temperature variations over more than 25 months post-infection. The results suggest that this non-lethal diagnostic test could be used in the future to improve the epidemiological surveillance and control of CyHV-3 disease. © 2016 John Wiley & Sons Ltd.

A novel, colorimetric neutralization assay for measuring antibodies to influenza viruses.

Science.gov (United States)

Lehtoranta, Liisa; Villberg, Anja; Santanen, Riitta; Ziegler, Thedi

2009-08-01

A colorimetric cell proliferation assay for measuring neutralizing antibodies to influenza viruses in human sera is described. Following a 90-min incubation, the serum-virus mixture was transferred to Madin-Darby canine kidney cells cultured in 96-well plates. After further incubation for three days, a tetrazolium salt was added to the wells. Cellular mitochondrial dehydrogenases cleave the tetrazolium salt to formazan, and the resulting color change is read by a spectrophotometer. The absorbance values correlate directly to the number of viable cells in the assay well and thus also to the neutralizing activity of influenza-specific antibodies present in the serum. With the few hands-on manipulations required, this assay allows simultaneous testing of a considerable number of sera, offers opportunities for automation, and is suitable for use under biosafety level-3 conditions. The test was used to study the antibody response after the administration of seasonal, inactivated, trivalent influenza vaccine. Antibody titers determined by the neutralization test in pre- and post-vaccination serum pairs were compared with those obtained by the hemagglutination inhibition assay. The neutralization test yielded higher pre- and post-vaccination titers and a larger number of significant increases in post-vaccination antibody titer than the hemagglutination inhibition test. This new test format could serve as a valuable laboratory tool for influenza vaccine studies.

Elemental analysis of human serum and serum protein fractions by thermal neutron activation

International Nuclear Information System (INIS)

Woittiez, J.R.W.

1984-01-01

Some applications of thermal neutron activation for the determination of elemental contents in human serum and human serum protein fractions are presented. Firstly total serum is dealt with, secondly serum protein fractions obtained by gel filtration are described. A brief review on the role of (trace) elements in human health and disease and a compilation of literature data for elemental contents in human serum, as obtained by neutron activation techniques, are given. The most important sources of statistical and systematic errors are evaluated. Results for the contents of sodium, potassium, magnesium, bromine, iron, copper, zinc, selenium, rubidium, cesium and antimony in serum are given, with emphasis on control of accuracy and precision. The possible relation between selenium in blood and cancer occurrence in humans is discussed. The results of elemental analyses from cancer patients and from a patient receiving a cytostatic treatment are presented. A survey of literature results for the determination of protein-bound elemental contents in serum is presented. Subsequently, results from a study on the behaviour of elements during gel filtration are discussed. Gel-element and protein-element interactions are studied. Finally the protein-bound occurrence of trace elements in human serum is determined by gel filtration and neutron activation analysis. Results for both desalting and fractionation are given, for the elements bromine, copper, manganese, vanadium, selenium, zinc, rubidium, iron and iodine. (Auth.)

Neutrality as Obstructionist in Academic Activism: Calling Bullshit

Science.gov (United States)

Rose, Barbara J.

2018-01-01

In this essay, the author uses experiences as a teacher educator and learning from a historically significant activism movement to (a) compare values in activism-centered and education-centered organizations, (b) posit ways that the concept of neutrality weakens academic activism, and (c) call for teacher education curricula and practices that…

Serum amylase and lipase activities after exploratory laparotomy in dogs.

Science.gov (United States)

Bellah, J R; Bell, G

1989-09-01

Serum amylase and lipase activities and creatinine concentration were determined before surgery, and at 1 and 2 days after exploratory laparotomy in 24 dogs. Examination of all viscera was done during each laparotomy, but a surgical procedure was not performed. The mean serum activities for lipase were: before surgery, 0.71 (0.0 to 2.0) Cherry Crandall units (CCU)/L; 1 day after surgery, 2.1 (0.0 to 4.5) CCU/L; and 2 days after surgery, 1.19 (0.0 to 3.9) CCU/L. The mean serum activities for amylase were: before surgery, 1,958 (1,027 to 3,426) IU/L; 1 day after surgery, 1,538 (937 to 2,659) IU/L; and 2 days after surgery, 1,663 (1,066 to 2,274) IU/L. Serum creatinine concentrations before surgery, 1 day after surgery, and 2 days after surgery were 0.88 (0.2 to 1.7) mg/dl, 0.78 (0.4 to 1.3) mg/dl, and 0.78 (0.3 to 1.3) mg/dl, respectively. Mean preoperative, day-1, and day-2 serum amylase activities and serum creatinine concentrations did not differ significantly from each other. Mean preoperative and day-2 serum lipase activities did not differ significantly; however, mean serum lipase activity was significantly greater when day 1 activities were compared with preoperative activities (P = 0.0002). Post-mortem examinations revealed no gross or histologic evidence of pancreatitis in any dog. The results of this study show that a 3 or more fold increase in serum lipase activity may occur after routine exploratory laparotomy in dogs without clinical signs or gross evidence of pancreatitis. Histologic evidence of pancreatitis was not found in the right pancreatic lobes in any dog.

Overcoming the inhibitory effect of serum on lipofection by increasing the charge ratio of cationic liposome to DNA.

Science.gov (United States)

Yang, J P; Huang, L

1997-09-01

Since cationic liposome was first developed as a lipofection reagent, a drawback has been noted in that the efficiency of lipofection decreases dramatically after addition of serum to the lipofection medium. This drawback hampers the application of cationic liposome for systematic delivery of genes. In the present studies, we found that the effect of serum on DC-chol liposome-mediated lipofection is dependent on the charge ratio of liposome to DNA. Serum inhibited lipofection activity of the lipoplex at low charge ratios, whereas it enhanced the lipofection activity at high charge ratios. This phenomenon was observed using DOTAP/DOPE but not lipofectamine. Measurement of cellular association of DNA showed that serum could reduce the binding of lipoplex to cells at all tested charge ratios, i.e. 0-10.6. Removal of negatively charged proteins from serum by DEAE Sephacel column abolished the inhibitory effect of serum on lipofection. The fraction contained only negatively charged serum proteins which strongly inhibited lipofection at low charge ratios but not at higher charge ratios. Furthermore, preincubation of serum with positively charged polylysine, which neutralized negatively charged serum proteins, eliminated the inhibitory effect of serum on lipofection. In summary, inactivation of cationic liposome by serum is due to negatively charged serum proteins and it can be overcome by increasing charge ratio of cationic liposome-DNA lipoplexes or by neutralizing the serum with polylysine.

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

Science.gov (United States)

Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

2017-01-01

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

Dengue-Immune Humans Have Higher Levels of Complement-Independent Enhancing Antibody than Complement-Dependent Neutralizing Antibody.

Science.gov (United States)

Yamanaka, Atsushi; Konishi, Eiji

2017-09-25

Dengue is the most important arboviral disease worldwide. We previously reported that most inhabitants of dengue-endemic countries who are naturally immune to the disease have infection-enhancing antibodies whose in vitro activity does not decrease in the presence of complement (complement-independent enhancing antibodies, or CiEAb). Here, we compared levels of CiEAb and complement-dependent neutralizing antibodies (CdNAb) in dengue-immune humans. A typical antibody dose-response pattern obtained in our assay system to measure the balance between neutralizing and enhancing antibodies showed both neutralizing and enhancing activities depending on serum dilution factor. The addition of complement to the assay system increased the activity of neutralizing antibodies at lower dilutions, indicating the presence of CdNAb. In contrast, similar dose-response curves were obtained with and without complement at higher dilutions, indicating higher levels of CiEAb than CdNAb. For experimental support for the higher CiEAb levels, a cocktail of mouse monoclonal antibodies against dengue virus type 1 was prepared. The antibody dose-response curves obtained in this assay, with or without complement, were similar to those obtained with human serum samples when a high proportion of D1-V-3H12 (an antibody exhibiting only enhancing activity and thus a model for CiEAb) was used in the cocktail. This study revealed higher-level induction of CiEAb than CdNAb in humans naturally infected with dengue viruses.

Modeling the LPS Neutralization Activity of Anti-Endotoxins

Directory of Open Access Journals (Sweden)

Virapong Prachayasittikul

2009-05-01

Full Text Available Bacterial lipopolysaccharides (LPS, also known as endotoxins, are major structural components of the outer membrane of Gram-negative bacteria that serve as a barrier and protective shield between them and their surrounding environment. LPS is considered to be a major virulence factor as it strongly stimulates the secretion of pro-inflammatory cytokines which mediate the host immune response and culminating in septic shock. Quantitative structure-activity relationship studies of the LPS neutralization activities of anti-endotoxins were performed using charge and quantum chemical descriptors. Artificial neural network implementing the back-propagation algorithm was selected for the multivariate analysis. The predicted activities from leave-one-out cross-validation were well correlated with the experimental values as observed from the correlation coefficient and root mean square error of 0.930 and 0.162, respectively. Similarly, the external testing set also yielded good predictivity with correlation coefficient and root mean square error of 0.983 and 0.130. The model holds great potential for the rational design of novel and robust compounds with enhanced neutralization activity.

Brain activation while forming memories of fearful and neutral faces in women and men.

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Fischer, Håkan; Sandblom, Johan; Nyberg, Lars; Herlitz, Agneta; Bäckman, Lars

2007-11-01

Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.

Activation of lipoprotein lipase by lipoprotein fractions of human serum.

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Bier, D M; Havel, R J

1970-11-01

Triglycerides in fat emulsions are hydrolyzed by lipoprotein lipase only when they are "activated" by serum lipoproteins. The contribution of different lipoprotein fractions to hydrolysis of triglycerides in soybean oil emulsion was assessed by determining the quantity of lipoprotein fraction required to give half-maximal hydrolysis. Most of the activator property of whole serum from normolipidemic, postabsorptive subjects was in high density lipoproteins. Low density lipoproteins and serum from which all lipoprotein classes were removed had little or no activity. Also, little activator was present in guinea pig serum or in very low density poor serum from an individual with lecithin:cholesterol acyltransferase deficiency, both of which are deficient in high density lipoproteins. Human very low density lipoproteins are potent activators and are much more active than predicted from their content of high density lipoprotein-protein. Per unit weight of protein, very low density lipoproteins had 13 times the activity of high density lipoproteins. These observations suggest that one or more of the major apoproteins of very low density lipoproteins, present as a minor constituent of high density lipoproteins, may be required for the activation process.

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

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Chaojun Qi

Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

Formation of Neutral Disk-Like Zone Around the Active Hot Stars in Symbiotic Binaries

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Cariková Z.

2012-06-01

Full Text Available In this contribution we present the ionization structure in the enhanced wind from the hot star in symbiotic binaries during active phases. Rotation of the hot star leads to the compression of the outflowing material towards its equatorial plane. As a result, a neutral disk-like zone around the active hot star near the orbital plane is created. We modeled the compression of the wind and calculated the neutral disk-like zone in the enhanced wind from the hot star using the equation of the photoionization equilibrium. the presence of such neutral disk-like zones was also suggested on the basis of the modeling the spectral energy distribution of symbiotic binaries. We confront the calculated ionization structures in the enhanced wind from the hot star with the observations. the calculated column density of the neutral hydrogen atoms in the neutral disk-like zone and the emission measure of the ionized part of the wind from the hot star are in a good agreement with the quantities derived from observations during active phases. the presence of such neutral disk-like zones is transient, being connected with the active phases of symbiotic binaries. During quiescent phases, such neutral disk-like zones cannot be created because of insufficient mass-loss rate from the hot star.

Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells.

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Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S; Nogueira, Lilian; Schoofs, Till; Krassnig, Lisa; Butler, Allison; Millard, Katrina; Fitzsimons, Tomas; Daniell, Xiaoju; Dizon, Juan P; Shimeliovich, Irina; Montefiori, David C; Caskey, Marina; Nussenzweig, Michel C

2018-03-01

Recently discovered broadly neutralizing antibodies (bNAbs) against HIV-1 demonstrate extensive breadth and potency against diverse HIV-1 strains and represent a promising approach for the treatment and prevention of HIV-1 infection. The breadth and potency of these antibodies have primarily been evaluated by using panels of HIV-1 Env-pseudotyped viruses produced in 293T cells expressing molecularly cloned Env proteins. Here we report on the ability of five bNAbs currently in clinical development to neutralize circulating primary HIV-1 isolates derived from peripheral blood mononuclear cells (PBMCs) and compare the results to those obtained with the pseudovirus panels used to characterize the bNAbs. The five bNAbs demonstrated significantly less breadth and potency against clinical isolates produced in PBMCs than against Env-pseudotyped viruses. The magnitude of this difference in neutralizing activity varied, depending on the antibody epitope. Glycan-targeting antibodies showed differences of only 3- to 4-fold, while antibody 10E8, which targets the membrane-proximal external region, showed a nearly 100-fold decrease in activity between published Env-pseudotyped virus panels and PBMC-derived primary isolates. Utilizing clonal PBMC-derived primary isolates and molecular clones, we determined that the observed discrepancy in bNAb performance is due to the increased sensitivity to neutralization exhibited by 293T-produced Env-pseudotyped viruses. We also found that while full-length molecularly cloned viruses produced in 293T cells exhibit greater sensitivity to neutralization than PBMC-derived viruses do, Env-pseudotyped viruses produced in 293T cells generally exhibit even greater sensitivity to neutralization. As the clinical development of bNAbs progresses, it will be critical to determine the relevance of each of these in vitro neutralization assays to in vivo antibody performance. IMPORTANCE Novel therapeutic and preventive strategies are needed to contain the

A regulatory hydrophobic area in the flexible joint region of plasminogen activator inhibitor-1, defined with fluorescent activity-neutralizing ligands. Ligand-induced serpin polymerization

DEFF Research Database (Denmark)

Egelund, R; Einholm, A P; Pedersen, K E

2001-01-01

by all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward u......PA, and second step is to forms inert to uPA. With some neutralizers, the second step was associated with PAI-1 polymerization. Vitronectin reduced the susceptibility to the neutralizers. Changes in sensitivity to activity neutralization by point mutations were compatible with the various neutralizers having...

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12

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Niloofar Shekoohi

2017-08-01

Full Text Available Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (P<0.001. This is one of the first studies that evaluated the serum level of active form of vitamin B12 in smokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

International Nuclear Information System (INIS)

Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

1995-01-01

The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential

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Larissa M. Alvarenga

2014-08-01

Full Text Available Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.

Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

Science.gov (United States)

Sun, Mingbo; Li, Changgui; Xu, Wenbo; Liao, Guoyang; Li, Rongcheng; Zhou, Jian; Li, Yanping; Cai, Wei; Yan, Dongmei; Che, Yanchun; Ying, Zhifang; Wang, Jianfeng; Yang, Huijuan; Ma, Yan; Ma, Lei; Ji, Guang; Shi, Li; Jiang, Shude; Li, Qihan

2017-05-15

A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. NCT01056705. © 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.

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12.

Science.gov (United States)

Shekoohi, Niloofar; Javanbakht, Mohammad Hassan; Sohrabi, Marjan; Zarei, Mahnaz; Mohammadi, Hamed; Djalali, Mahmoud

2017-06-01

Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (Psmokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

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

Science.gov (United States)

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

2013-07-01

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

Serum creatine kinase and lactate dehydrogenase activities in ...

African Journals Online (AJOL)

Background and Objectives: There is the recognition of a pattern of elevations of serum enzymes in hyperthyroid and hypothyroid patients. The aims of this study were to determine the activities of serum creatine kinase (CK) and lactate deydrogenase (LDH) in thyroid disorders, and to evaluate the relationship between CK, ...

The stability of complement-mediated bactericidal activity in human serum against Salmonella.

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Colette M O'Shaughnessy

Full Text Available The complement cascade includes heat-labile proteins and care is required when handling serum in order to preserve its functional integrity. We have previously used a whole human serum bactericidal assay to show that antibody and an intact complement system are required in blood for killing of invasive isolates of Salmonella. The aim of the present study was to evaluate the conditions under which human serum can be stored and manipulated while maintaining complement integrity. Serum bactericidal activity against Salmonella was maintained for a minimum of 35 days when stored at 4°C, eight days at 22°C and 54 hours at 37°C. Up to three freeze-thaw cycles had no effect on the persistence of bactericidal activity and hemolytic complement assays confirmed no effect on complement function. Delay in the separation of serum for up to four days from clotted blood stored at 22°C did not affect bactericidal activity. Dilution of serum resulted in an increased rate of loss of bactericidal activity and so serum should be stored undiluted. These findings indicate that the current guidelines concerning manipulation and storage of human serum to preserve complement integrity and function leave a large margin for safety with regards to bactericidal activity against Salmonella. The study provides a scheme for determining the requirements for serum handling in relation to functional activity of complement in other systems.

Serum prolidase activity and oxidative status in Helicobacter pylori infection.

Science.gov (United States)

Aslan, Mehmet; Nazligul, Yasar; Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Aksoy, Nurten; Celik, Hakim; Erel, Ozcan

2007-01-01

During the course of Helicobacter pylori infection, increased oxidative stress plays an important role in the pathogenesis of gastroduodenal mucosal inflammation, which can cause gastric mucosal atrophy that characterized by the replacement of the gastric mucosal glands by collagen fibers. In the present study, we aimed to determine serum prolidase activity and oxidative status, and to find out if there is any association between serum prolidase activity and oxidative status in H. pylori infection. Forty H. pylori-positive and 32 H. pylori-negative subjects were enrolled. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity and total oxidant status measurement and calculation of oxidative stress index. Total antioxidant capacity level was lower in H. pylori-positive group than H. pylori-negative group (ptotal oxidant status, oxidative stress index and prolidase activity were higher (all ptotal antioxidant capacity, total oxidant status and oxidative stress index (p<0.01, r=-0.367; p<0.05, r=0.283; p<0.01, r=0.379; respectively) in H. pylori-positive subjects. H. pylori infection may be associated with increased oxidative stress and increased serum prolidase activity. Increased oxidative stress seems to be associated with increased serum prolidase activity and this association may help to provide a better understanding about the pathogenesis of H. pylori infection.

Oxidative status and serum PON1 activity in beta-thalassemia minor.

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Selek, Sahbettin; Aslan, Mehmet; Horoz, Mehmet; Gur, Mustafa; Erel, Ozcan

2007-03-01

Paraoxonase-1 (PON1) deficiency is related to increased susceptibility to low density lipoprotein oxidation and development of atherosclerosis. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters, and to find out if there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum PON1 activity in beta-thalassemia minor (BTM) subjects. Thirty-two subjects with BTM and 28 healthy subjects as control were enrolled in the study. Serum paraoxonase and arylesterase activities, lipid hydroperoxide (LOOH) levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum TAC, paraoxonase and arylesterase activities were significantly lower in BTM subjects than controls (for all p<0.001), while TOS, LOOH levels and OSI were significantly higher (p<0.001, p<0.05 and p<0.001; respectively). In BTM subjects, OSI, TOS, LOOH levels and TAC were significantly correlated with serum paraoxonase (r=-0.245, p<0.05; r=-0.231, p<0.05; r=-0.264, p<0.05 and, r=0.342, p<0.05, respectively) and arylesterase activities (r=-0.332, p<0.05, r=-0.308, p<0.05; r=-0.320, p<0.05 and r=0.443, p<0.05). Additionally, hemoglobin level was also correlated with serum paraoxonase (r=0.501, p<0.001) and arylesterase activities (r=0.501, p<0.001), TAC (r=0.402, p<0.05), TOS (r=-0.274, p<0.05) and OSI (r=-0.352, p<0.05). Oxidative stress is increased, while serum PON1 activity is decreased in BTM subjects. Decrease in PON1 activity seems to be associated with both the degree of oxidative stress and anemia. BTM subjects may be more prone to development of atherogenesis due to low serum PON1 activity.

Analysis of activation and shutdown contact dose rate for EAST neutral beam port

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Chen, Yuqing; Wang, Ji; Zhong, Guoqiang; Li, Jun; Wang, Jinfang; Xie, Yahong; Wu, Bin; Hu, Chundong

2017-12-01

For the safe operation and maintenance of neutral beam injector (NBI), specific activity and shutdown contact dose rate of the sample material SS316 are estimated around the experimental advanced superconducting tokamak (EAST) neutral beam port. Firstly, the neutron emission intensity is calculated by TRANSP code while the neutral beam is co-injected to EAST. Secondly, the neutron activation and shutdown contact dose rates for the neutral beam sample materials SS316 are derived by the Monte Carlo code MCNP and the inventory code FISPACT-2007. The simulations indicate that the primary radioactive nuclides of SS316 are 58Co and 54Mn. The peak contact dose rate is 8.52 × 10-6 Sv/h after EAST shutdown one second. That is under the International Thermonuclear Experimental Reactor (ITER) design values 1 × 10-5 Sv/h.

Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation.

Science.gov (United States)

Heinz, Andreas; Smolka, Michael N; Braus, Dieter F; Wrase, Jana; Beck, Anne; Flor, Herta; Mann, Karl; Schumann, Gunter; Büchel, Christian; Hariri, Ahmad R; Weinberger, Daniel R

2007-04-15

A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (l) carriers. However, a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. Amygdala activation was increased in s carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful.

Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles.

Science.gov (United States)

Moeschler, Sarah; Locher, Samira; Conzelmann, Karl-Klaus; Krämer, Beate; Zimmer, Gert

2016-09-16

Rabies is a highly fatal zoonotic disease which is primarily caused by rabies virus (RABV) although other members of the genus Lyssavirus can cause rabies as well. As yet, 14 serologically and genetically diverse lyssaviruses have been identified, mostly in bats. To assess the quality of rabies vaccines and immunoglobulin preparations, virus neutralization tests with live RABV are performed in accordance with enhanced biosafety standards. In the present work, a novel neutralization test is presented which takes advantage of a modified vesicular stomatitis virus (VSV) from which the glycoprotein G gene has been deleted and replaced by reporter genes. This single-cycle virus was trans-complemented with RABV envelope glycoprotein. Neutralization of this pseudotype virus with RABV reference serum or immune sera from vaccinated mice showed a strong correlation with the rapid fluorescent focus inhibition test (RFFIT). Importantly, pseudotype viruses containing the envelope glycoproteins of other lyssaviruses were neutralized by reference serum to a significantly lesser extent or were not neutralized at all. Taken together, a pseudotype virus system has been successfully developed which allows the safe, fast, and sensitive detection of neutralizing antibodies directed against different lyssaviruses.

Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles

Directory of Open Access Journals (Sweden)

Sarah Moeschler

2016-09-01

Full Text Available Rabies is a highly fatal zoonotic disease which is primarily caused by rabies virus (RABV although other members of the genus Lyssavirus can cause rabies as well. As yet, 14 serologically and genetically diverse lyssaviruses have been identified, mostly in bats. To assess the quality of rabies vaccines and immunoglobulin preparations, virus neutralization tests with live RABV are performed in accordance with enhanced biosafety standards. In the present work, a novel neutralization test is presented which takes advantage of a modified vesicular stomatitis virus (VSV from which the glycoprotein G gene has been deleted and replaced by reporter genes. This single-cycle virus was trans-complemented with RABV envelope glycoprotein. Neutralization of this pseudotype virus with RABV reference serum or immune sera from vaccinated mice showed a strong correlation with the rapid fluorescent focus inhibition test (RFFIT. Importantly, pseudotype viruses containing the envelope glycoproteins of other lyssaviruses were neutralized by reference serum to a significantly lesser extent or were not neutralized at all. Taken together, a pseudotype virus system has been successfully developed which allows the safe, fast, and sensitive detection of neutralizing antibodies directed against different lyssaviruses.

Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

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Yutaka Aoki

2014-01-01

Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.

Complex nature of serum lysozyme activity: evidence of thermolability in inflammatory bowel disease

Energy Technology Data Exchange (ETDEWEB)

Ward, M; Mitchell, W D; Eastwood, M [Western General Hospital, Edinburgh (UK)

1978-01-01

In patients with Crohn's disease and ulcerative colitis, alterations in serum storage temperature produced significant changes in serum lysozyme activity (SLA) as measured by the lysoplate method. This was not the case in healthy controls or in a group with other gastrointestinal disorders. Electrophoretic separation of serum revealed two components of lysozyme-type lytic activity but only one in extracts of gut mucosa, leucocytes, and egg white. The major lytic component of serum migrated towards the cathode and reacted with specific antilysozyme serum, but the minor component which migrated towards the anode did not. Although the cause of this anionic lytic activity is uncertain, it contributes to total serum activity as estimated by any method utilizing the lysis of Micrococcus lysodeikticus, and may possibly be related to the observed thermolability.

Neutralization of toxicological activities of medically-relevant Bothrops snake venoms and relevant toxins by two polyvalent bothropic antivenoms produced in Peru and Brazil.

Science.gov (United States)

Estevao-Costa, Maria I; Gontijo, Silea S; Correia, Barbara L; Yarleque, Armando; Vivas-Ruiz, Dan; Rodrigues, Edith; Chávez-Olortegui, Carlos; Oliveira, Luciana S; Sanchez, Eladio F

2016-11-01

Snakebite envenoming is a neglected public pathology, affecting especially rural communities or isolated areas of tropical and subtropical Latin American countries. The parenteral administration of antivenom is the mainstay and the only validated treatment of snake bite envenoming. Here, we assess the efficacy of polyspecific anti-Bothrops serum (α-BS) produced in the Instituto Nacional de Salud (INS, Peru) and at the Fundação Ezequiel Dias (FUNED, Brazil), to neutralize the main toxic activities induced by five medically-relevant venoms of: Bothrops atrox, B. barnetti, and B. pictus from Peru, and the Brazilian B. jararaca and B. leucurus, all of them inhabiting different geographical locations. Protein electrophoretic patterns of these venoms showed significant differences in composition, number and intensity of bands. Another goal was to evaluate the efficacy and safety of lyophilized α-BS developed at INS to neutralize the detrimental effects of these venoms using in vivo and in vitro assays. The availability of lyophilized α-BS has relevant significance in its distribution to distant rural communities where the access to antivenom in health facilities is more difficult. Despite the fact that different antigen mixtures were used for immunization during antivenom production, our data showed high toxin-neutralizing activity of α-BS raised against Bothrops venoms. Moreover, the antivenom cross-reacted even against venoms not included in the immunization mixture. Furthermore, we have evaluated the efficacy of both α-BS to neutralize key toxic compounds belonging to the predominant protein families of Bothrops snakes. Most significantly, both α-BS cross-specifically neutralized the main toxicological activities e.g. lethality and hemorrhage induced by these venoms. Thus, our data indicate that both α-BS are equally effective to treat snake bite victims inflicted by Bothrops snakes particularly B. atrox, responsible for the largest numbers of human

Increased serum cortisol binding in chronic active hepatitis

International Nuclear Information System (INIS)

Orbach, O.; Schussler, G.C.

1989-01-01

A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

Comparison of humoral immune response, neutralization capacity of anticrotalic serum in young ovines, clinical and weight evaluation between animals inoculated with Crotalus durissus terrificus venom, natural or Cobalt-60-irradiated

International Nuclear Information System (INIS)

Ferreira Junior, R.S.

2005-01-01

The Elisa technique was used to evaluate and compare the humoral immune response of young ovine to anticrotalic serum production. During serum production, the clinical and weight evaluation of the animals was performed. The parameters utilized were complete blood count, and dosage of urea, creatinine, aspartate aminotransferase, total proteins, albumin and globulin. The animals weight was verified fortnightly during the experiment. The neutralization capacity of the serum produced from the snake Crotalus durissus terrificus natural (NV) and Cobalt-60-irradiated venom (IrV) was evaluated by in vitro challenges. One group of six animals received natural venom, the second group received irradiated venom, and the third was the control group. The animals received six immunizations during 84 days with an interval of 14 days. There was a significant difference (p<5%) in the ELISA test for the profile of the antibodies produced by the experimental groups (NV< IrV). There was no significant difference (p<5%) for biochemical tests, complete blood count, and animals weight between the three groups tested. The group immunized with irradiated venom showed antibodies profile higher than the group immunized with natural venom. The neutralization capacity of the serum produced from the IrV was fivefold higher when compared to the serum produced with NV. The clinical and weight evaluation showed that the o vines in post-weaning phase did not have their physiological profiles altered, and showed an excellent increase in weight during the experimental period. These results indicate a new perspective for the utilization of o vines, aiming the commercial production of anticrotalic serum, which may be applied in the treatment of human and animal envenomation. The cost for its production may be reduced by the posterior utilization of hyperimmunized ovine in human feeding. (author)

Comparison of humoral immune response, neutralization capacity of anticrotalic serum in young ovines, clinical and weight evaluation between animals inoculated with Crotalus durissus terrificus venom, natural or Cobalt-60-irradiated

Energy Technology Data Exchange (ETDEWEB)

Ferreira Junior, R.S. E-mail: rseabra@cevap.org.br

2005-07-01

The Elisa technique was used to evaluate and compare the humoral immune response of young ovine to anticrotalic serum production. During serum production, the clinical and weight evaluation of the animals was performed. The parameters utilized were complete blood count, and dosage of urea, creatinine, aspartate aminotransferase, total proteins, albumin and globulin. The animals weight was verified fortnightly during the experiment. The neutralization capacity of the serum produced from the snake Crotalus durissus terrificus natural (NV) and Cobalt-60-irradiated venom (IrV) was evaluated by in vitro challenges. One group of six animals received natural venom, the second group received irradiated venom, and the third was the control group. The animals received six immunizations during 84 days with an interval of 14 days. There was a significant difference (p<5%) in the ELISA test for the profile of the antibodies produced by the experimental groups (NVneutralization capacity of the serum produced from the IrV was fivefold higher when compared to the serum produced with NV. The clinical and weight evaluation showed that the o vines in post-weaning phase did not have their physiological profiles altered, and showed an excellent increase in weight during the experimental period. These results indicate a new perspective for the utilization of o vines, aiming the commercial production of anticrotalic serum, which may be applied in the treatment of human and animal envenomation. The cost for its production may be reduced by the posterior utilization of hyperimmunized ovine in human feeding. (author)

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

Science.gov (United States)

Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

2017-05-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

Relation of serum γ-glutamyl transferase activity with copper in an adult population.

Science.gov (United States)

Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

2017-10-26

The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, pcopper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, pcopper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure

DEFF Research Database (Denmark)

Andersen, Helle Raun; Nielsen, Flemming; Nielsen, Jesper Bo

2007-01-01

-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. Conclusions: The study illustrates the usefulness of this biomarker for qualitative assessment...... with oestrogen-like properties in an occupational setting. Methods: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity......, medium or high based on information collected by detailed interviews of the women and the employers. Results: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno...

Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide

International Nuclear Information System (INIS)

Hopfer, S.M.; Sunderman, F.W. Jr.; Fredrickson, T.N.; Morse, E.E.

1979-01-01

To investigate the pathopysiologic mechanisms of nickel-induced erythocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of αNi 3 S 2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was approx. = 20 I.U./liter of serum. In mice which received pooled serum from αNi 3 S 2 -treated rats, erythrocyte 59 Fe-uptake averaged 28% (S.D. +- 5) (vs 3.7 +- 1.1% in control rats; P 3 S 2 -treated rats averaged 130 I.U./liter (S.D. +- 18) (vs 27 +- 6 I.U./liter in control rats; P 3 S 2 is mediated by increased serum erythropoietin activity

Serum components and clinical efficacies of autologous serum eye drops in dry eye patients with active and inactive Sjogren syndrome.

Science.gov (United States)

Ma, I-Hsin; Chen, Lily Wei; Tu, Wen-Hui; Lu, Chia-Ju; Huang, Chien-Jung; Chen, Wei-Li

2017-01-01

Autologous serum eye drops are considered safe and efficient for the treatment of various ocular surface disorders, including dry eye diseases (DED) caused by the primary and secondary Sjogren syndrome (SS). However, the serum components in patients of SS may be different from those of normal patients and can thus lead to unpredictable therapeutic effects. This study divided the SS patients into active and inactive types based on the erythrocyte sedimentation rate and the presence or absence of active rheumatoid arthritis. We compared the serum components of these two groups with standard and multiplex enzyme linked immunosorbent assay arrays and predicted the therapeutic effects of topical autologous serum for the treatment of DED with ocular surface disease index (OSDI) and Oxford Schema scale (OSS). Hyaluronic acid and transforming growth factor b1 levels were significantly higher in the active SS group compared to the inactive SS group ( P Sjogren dry eye patients into active and inactive groups may appear as a reasonable method to predict the quality of autologous serum eye drops, but there seems to be no significant predictability to the therapeutic effects.

Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.

Science.gov (United States)

deCamp, Allan; Hraber, Peter; Bailer, Robert T; Seaman, Michael S; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K; Zolla-Pazner, Susan; LaBranche, Celia C; Mascola, John R; Korber, Bette T; Montefiori, David C

2014-03-01

Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit

Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

Science.gov (United States)

González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

2018-01-01

Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

Antibodies against Marinobacter algicola and Salmonella typhimurium flagellins do not cross-neutralize TLR5 activation.

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Raul Terron-Exposito

Full Text Available Flagellins evoke strong innate and adaptive immune responses. These proteins may play a key role as radioprotectors, exert antitumoral activity in certain types of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients. Notwithstanding, flagellins are highly immunogenic, and repeated use leads to their neutralization by systemic antibodies. This neutralization is not prevented by using functional deleted flagellins. These observations led us to explore the possibility of preventing initial neutralization by means of another functional flagellin that does not belong to common pathogenic bacteria but that has the capacity to activate TLR5. Here we characterized the functional capacity of the two-phase Marinobacter algicola (MA-derived flagellins (F and FR as systemic and mucosal adjuvants and compared their performance with that of Salmonella typhimurium (STF flagellins (FljB and FliC. We also report for the first time on the in vitro and in vivo capacity of various flagellins to trigger TLR5 activation in the presence of species-specific anti-flagellin antibodies, the cross-neutralization mediated by these antibodies, and the sequential use of these flagellins for TLR5 activation. Our results showed that MA flagellins behave in a similar way to STF ones, inducing pro-inflammatory cytokines (IL8, CCL20, CCL2 and evoking a strong in vivo antibody response against a model epitope. More importantly, MA flagellins were fully functional, in vitro or in vivo, in the presence of a high concentration of neutralizing anti-flagellin STF antibodies, and STF flagellin was not inhibited by neutralizing anti-flagellin MA antibodies. The use of active flagellins from distinct bacteria could be a useful approach to prevent systemic neutralization of this group of adjuvants and to facilitate the rational design of flagellin-based vaccines and/or other therapeutic treatments (against ischemia, acute renal failure

In vitro demonstration of anti-lipogenic activity in serum from obese rats

International Nuclear Information System (INIS)

Harris, R.B.S.; Martin, R.J.

1986-01-01

Studies with parabiosed rats provide evidence for a humoral factor, originating in obese animals, that specifically inhibits adipose lipogenesis. A bioassay was developed that allows serum from obese rats to be tested for this factor in vitro. Adipocytes are isolated from epididymal fat of 250g Sprague-Dawley rats. The cells are preincubated at 37 0 C for 1 or 12 hrs, in TC199 media containing 1.1 mg/ml glucose, 0.1 M Hepes and 2% serum. Following preincubation, the cells are washed 3 times and resuspended in serum-free media. Aliquots of cells are tested for metabolic activity in a subsequent 2 hour radiolabelled incubation in serum-free media with the addition of 0.5 μCi/ml U- 14 C-glucose. Basal, insulin (100 μU/ml) and norepinephrine (0.1 μg/ml) stimulated rates of glucose oxidation and conversion to triglyceride fatty acids are measured. Using serum from ad libitum fed rats as control, preincubation with serum from obese rats (20 days at 2 x normal intake) depressed basal and insulin stimulated glucose oxidation, and basal fatty acid synthesis. Serum from obese parabiotic rats and parabiotic partners of obese rats depressed basal fatty acid synthesis. This assay allows us to test serum for anti-lipogenic activity and may be used to identify the factor responsible for this activity in obese animals

New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

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Joanna Jońca

Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

Science.gov (United States)

Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

2015-01-01

Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESNHIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

The effect of electro-activation and eggshell powder on the neutralization of acid mine drainage

Directory of Open Access Journals (Sweden)

Alexey Kastyuchik

2017-01-01

Full Text Available Acid mine drainage (AMD production by sulfide mine tailing (SMT is a major environmental preoccupation because it can degrade water surface quality on account of its strong acidity and advanced content of sulfide, iron (Fe and other metals and metalloids. Acid neutralization and the precipitation of metals present in AMD were carried out by electro-activation with ion-exchange membranes, which is based on the self-generation of necessary conditions for acid neutralization and metal precipitation. The treatment of SMT was carried out by using an electro-activation cell generated alkaline solution in the cathode compartment. After 60 min of electro-activation, a pHcatholyte of 7.9–9.6, depending on the experimental conditions, was obtained. The absence of Fe and other trace metal ions in the catholyte provide evidence that the electro-activation of SMT promotes the precipitation of insoluble trace metals in the cathode compartment. This approach can be applied to real conditions in combination with a pretreatment of SMT neutralization, in which biological calcareous amendments are available. Finally, the electro-activation technology of acid mine drainage may be a feasible, cost-effective approach for SMT neutralization because it focuses on sustainable development.

Method of active charge and current neutralization of intense ion beams for ICF

International Nuclear Information System (INIS)

Guiragossian, Z.G.T.; Orthel, J.L.; Lemons, D.S.; Thode, L.E.

1981-01-01

Methods of generating the beam neutralization electrons with required properties are given in the context of a Light Ion Fusion Experiment (LIFE) designed accelerator. Recently derived envelope equations for neutralized and ballistically focused intense ion beams are applied to the LIFE geometry in which 10 MeV He + multiple beamlets coalesce and undergo 45:1 radial compression while beam pulses experience a 20:1 axial compression in the propagation range of 10 m. Both active and auto-neutralization methods are examined and found to produce initial electron temperatures consistent with the requirement of the envelope equation for both radial and axial adiabatic beam pulse compressions. The stability of neutralized beam propagation is also examined concerning the Pierce type electrostatic instability and for the case of LIFE beams it is found to have insignificant effect. A scaled experimental setup is presented which can serve to perform near term tests on the ballistically focused propagation of neutralized light ion beams

Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

Science.gov (United States)

Carvajal, Fernando; Rubio, Sandra; Serrano, Juan M; Ríos-Lago, Marcos; Alvarez-Linera, Juan; Pacheco, Lara; Martín, Pilar

2013-08-01

Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.

Enterovirus 71 Neutralizing Antibodies Seroepidemiological Research among Children in Guangzhou, China between 2014 and 2015: A Cross-Sectional Study.

Science.gov (United States)

Zhang, Dingmei; Chen, Yan; Chen, Xiashi; He, Zhenjian; Zhu, Xun; Hao, Yuantao

2017-03-20

A hand-foot-mouth disease outbreak occurred in 2014 around Guangdong. The purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. Serum specimens were collected from children in communities from January 2014 to March 2015 in Guangzhou. A total of 197 serum samples from children 1-5 years old were collected for this cross-sectional study via non-probabilistic sampling from the database of Chinese National Science and Technique Major Project. Neutralization activity was measured via micro neutralization test in vitro. The positive rate of enterovirus 71 neutralizing antibodies was 59.4%, whereas the geometric mean titre was 1:12.7. A statistically significant difference in true positive rates was found between different age groups but not between different genders. Being the most susceptible population of hand-foot-mouth disease, children under 3 years of age are more likely to be infected with enterovirus 71, and the immunity of children increases with increasing age. Further cohort studies should be conducted, and measures for prevention and vaccination should be taken.

Enterovirus 71 Neutralizing Antibodies Seroepidemiological Research among Children in Guangzhou, China between 2014 and 2015: A Cross-Sectional Study

Directory of Open Access Journals (Sweden)

Dingmei Zhang

2017-03-01

Full Text Available A hand-foot-mouth disease outbreak occurred in 2014 around Guangdong. The purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. Serum specimens were collected from children in communities from January 2014 to March 2015 in Guangzhou. A total of 197 serum samples from children 1–5 years old were collected for this cross-sectional study via non-probabilistic sampling from the database of Chinese National Science and Technique Major Project. Neutralization activity was measured via micro neutralization test in vitro. The positive rate of enterovirus 71 neutralizing antibodies was 59.4%, whereas the geometric mean titre was 1:12.7. A statistically significant difference in true positive rates was found between different age groups but not between different genders. Being the most susceptible population of hand–foot–mouth disease, children under 3 years of age are more likely to be infected with enterovirus 71, and the immunity of children increases with increasing age. Further cohort studies should be conducted, and measures for prevention and vaccination should be taken.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

Science.gov (United States)

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

Science.gov (United States)

Zureik, Mahmoud; Robert, Ladislas; Courbon, Dominique; Touboul, Pierre-Jean; Bizbiz, Latifa; Ducimetière, Pierre

2002-06-04

In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

Detection of canine distemper virus serum neutralizing antibodies in captive U.S. phocids.

Science.gov (United States)

Clancy, Meredith M; Gamble, Kathryn C; Travis, Dominic A

2013-03-01

Antibodies to morbilliviruses have been documented in free-ranging pinnipeds throughout populations in the Atlantic and Arctic Oceans, but not from the Pacific Ocean. As a symbolic geographic barrier between the exposed Atlantic and naive Pacific populations, the captive phocid population in North America had undocumented serologic status. In this study, canine distemper virus (CDV) serum neutralization assays were used to assess the prevalence of antibodies in this population with participation of 25 U.S. institutions from grey seals (Halichoerus grypus, n = 6) and harbor seals (Phoca vitulina, n = 108). Historic and environmental risk factors associated with the epidemiology of distemper virus were collected by survey. Based on antibodies to canine distemper virus, the prevalence of exposure in this population was 25.5%, with 28 seals (grey, n = 2; harbor, n = 26) demonstrating antibody titers > or = 1:16, and positive titers ranged from 1:4 to 1:1,536. By survey analysis, strong associations with seropositive status were identified for captive origin (P = 0.013) and movement among institutions (P = 0.024). Size of population has positive correlation with likelihood of seropositive seals at an institution (P = 0.020). However, no major husbandry or enclosure-based risk factors were identified in institutions with seropositive seals, and no interaction between individual or institutional risk factors was identified. Previously undocumented prior to this study, CDV antibodies were measured in harbor seals (n = 2) recently stranded from the Pacific coast.

INFLUENCE OF BIOPREPARATIONS FROM DRY SOYBEAN AND SUNFLOWER LECITHINS ON SERUM LIPIDS COMPOSITION

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H. V. Dziak

2014-04-01

Full Text Available Dry lecithin, which is a mixture of polar phospholipids, neutral lipids, free fatty acids, glycolipids, carbohydrates, and small amounts of moisture, is a promising object for biologic-hepatoprotectors creation. One of its pharmacological activity displays is its influence on serum lipids, in particular transport forms of these lipids. The influence of dry soy lecithin and sunflower on hyperlipoproteinemia ratio and other lipid disorders is studied. It is shown that low-fat dry soybean lecithin showed hypocholesterolemic activity against all studied forms of serum cholesterol. Nonfat dry sunflower lecithin had similar but somewhat less prominent effect. However reduced concentration of high density lipoprotein cholesterol under sunflower lecithin developed right before soya lecithin. Both lecithin prevented the development of dyslipidemia induced carbon tetrachloride.

Characterization of Serum Phospholipase A2 Activity in Three Diverse Species of West African Crocodiles

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Mark Merchant

2011-01-01

Full Text Available Secretory phospholipase A2, an enzyme that exhibits substantial immunological activity, was measured in the serum of three species of diverse West African crocodiles. Incubation of different volumes of crocodile serum with bacteria labeled with a fluorescent fatty acid in the sn-2 position of membrane lipids resulted in a volume-dependent liberation of fluorescent probe. Serum from the Nile crocodile (Crocodylus niloticus exhibited slightly higher activity than that of the slender-snouted crocodile (Mecistops cataphractus and the African dwarf crocodile (Osteolaemus tetraspis. Product formation was inhibited by BPB, a specific PLA2 inhibitor, confirming that the activity was a direct result of the presence of serum PLA2. Kinetic analysis showed that C. niloticus serum produced product more rapidly than M. cataphractus or O. tetraspis. Serum from all three species exhibited temperature-dependent PLA2 activities but with slightly different thermal profiles. All three crocodilian species showed high levels of activity against eight different species of bacteria.

A safe and reliable neutralization assay based on pseudovirus to measure neutralizing antibody titer against poliovirus.

Science.gov (United States)

Liu, Shaohua; Song, Dongmei; Bai, Han; Lu, Weiwei; Dai, Xinxian; Hao, Chunsheng; Zhang, Zhongyang; Guo, Huijie; Zhang, Yue; Li, Xiuling

2017-12-01

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping. © 2017 Wiley Periodicals, Inc.

[Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus].

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Blum, C; Zillikens, D; Tony, H P; Hartmann, A A; Burg, G

1993-05-01

The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.

Chemical acceleration of a neutral granulated blast-furnace slag activated by sodium carbonate

International Nuclear Information System (INIS)

Kovtun, Maxim; Kearsley, Elsabe P.; Shekhovtsova, Julia

2015-01-01

This paper presents results of a study on chemical acceleration of a neutral granulated blast-furnace slag activated using sodium carbonate. As strength development of alkali-activated slag cements containing neutral GBFS and sodium carbonate as activator at room temperature is known to be slow, three accelerators were investigated: sodium hydroxide, ordinary Portland cement and a combination of silica fume and slaked lime. In all cements, the main hydration product is C–(A)–S–H, but its structure varies between tobermorite and riversideite depending on the accelerator used. Calcite and gaylussite are present in all systems and they were formed due to either cation exchange reaction between the slag and the activator, or carbonation. With accelerators, compressive strength up to 15 MPa can be achieved within 24 h in comparison to 2.5 MPa after 48 h for a mix without an accelerator

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

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Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, Pbilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

Serum creatine kinase and lactate dehydrogenase activities in ...

African Journals Online (AJOL)

... in thyroid function are common endocrine disorders affecting 5-10% of individuals over ... Key words: Hyperthyroidism, hypothyroidism, lactate dehydrogenase, serum creatine kinase ... individuals depends on age, race, lean body mass and physical activity. ... measured by radioimmunoassay on AXSYM System (Abbott.

Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.

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Gupta, Mamta; Han, Jing Jing; Stenson, Mary; Maurer, Matthew; Wellik, Linda; Hu, Guangzhen; Ziesmer, Steve; Dogan, Ahmet; Witzig, Thomas E

2012-03-22

Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL-10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up-regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL-10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy.

Antibody neutralization of retargeted measles viruses

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Lech, Patrycja J.; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J.; Nara, Peter L.; Russell, Stephen J.

2014-01-01

The measles virus (MV) vaccine lineage is a promising oncolytic but prior exposure to the measles vaccine or wild-type MV strains limits treatment utility due to the presence of anti-measles antibodies. MV entry can be redirected by displaying a polypeptide ligand on the Hemagglutinin (H) C-terminus. We hypothesized that retargeted MV would escape neutralization by monoclonal antibodies (mAbs) recognizing the H receptor-binding surface and be less susceptible to neutralization by human antisera. Using chimeric H proteins, with and without mutations that ablate MV receptor binding, we show that retargeted MVs escape mAbs that target the H receptor-binding surface by virtue of mutations that ablate infection via SLAM and CD46. However, C-terminally displayed domains do not mediate virus entry in the presence of human antibodies that bind to the underlying H domain. In conclusion, utility of retargeted oncolytic measles viruses does not extend to evasion of human serum neutralization. PMID:24725950

Serum paraoxonase activity and lipid hydroperoxide levels in adult ...

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Objectives: In this study, we aimed to investigate serum PON1 activity and lipid hydroperoxide (LOOH) levels in adult football players after three days ... oxidative stress after three days football tournament. In addition, physical activity for a ... polymorphism, gender, and exercise. Furthermore, it has been ...

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

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Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of aerobic activity on serum IgG concentration in male physical education students

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Arshadi Arshadi

2012-12-01

Full Text Available The aim of this study was to investigate the effects of aerobic activity on Serum IgG concentration. Consequently, 10 male physical education students with age ranging from 21 to 24 years old and mean body mass index 22.22 kg m2 volunteered to participate in this study. Aerobic activity was performed on bicycle ergometer for 30 minutes at intensity of 70 to 75 percent of maximum heart rate. Blood samples were obtained from subjects before and after aerobic activity. Changes in serum IgG concentration in pre-test and post-test were analyzed by dependent t-test using spss software. The results showed that aerobic activity not significantly effect on Serum IgG concentration (p=0.357. This study concludes that sub maximal aerobic activity does not affect on serum IgG concentration and there is no concern for athletes and coaches that sub maximal aerobic activity can impair immune function.

Lumbar lordosis angle and trunk and lower-limb electromyographic activity comparison in hip neutral position and external rotation during back squats.

Science.gov (United States)

Oshikawa, Tomoki; Morimoto, Yasuhiro; Kaneoka, Koji

2018-03-01

[Purpose] To compare the lumbar lordosis angle and electromyographic activities of the trunk and lower-limb muscles in the hip neutral position and external rotation during back squats. [Subjects and Methods] Ten healthy males without severe low back pain or lower-limb injury participated in this study. The lumbar lordosis angle and electromyographic activities were measured using three-dimensional motion-capture systems and surface electrodes during four back squats: parallel back squats in the hip neutral position and external rotation and full back squats in the hip neutral position and external rotation. A paired t-test was used to compare parallel and full back squats measurements in the hip neutral position and external rotation, respectively. [Results] During parallel back squats, the average lumbar lordosis angle was significantly larger in hip external rotation than in the hip neutral position. During full back squats, lumbar erector spinae and multifidus activities were significantly lower in hip external rotation than in the hip neutral position, whereas gluteus maximus activity was significantly higher in hip external rotation than in the hip neutral position. [Conclusion] The back squat in hip external rotation induced improvement of lumbar kyphosis, an increasing of the gluteus maximus activity and a decrease of both lumbar erector spinae and multifidus activities.

Effect of gamma radiation on tissue elastin content and serum elastolytic activity in rats

International Nuclear Information System (INIS)

Drozdz, M.; Olczyk, K.; Piwowarczyk, B.; Stawiarska, B.

1981-01-01

The elastin content of aorta, heart, skin and lungs as well as the serum elastolytic activity were determined in rats exposed to radiation. It was found that a single irradiation of rats with gamma rays (500 r) caused a decrease of the elastin content in all examined tissues. The serum elastolytic activity in the irradiated rats was increased. It is suggested that elastin degradation following radiation may be caused by changes in its molecular structure and possibly, due to increased serum elastolytic activity. (author)

Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa.

Science.gov (United States)

van West, D; Monteleone, P; Di Lieto, A; De Meester, I; Durinx, C; Scharpe, S; Lin, A; Maj, M; Maes, M

2000-01-01

The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders.

Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins

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James Richard W

2010-09-01

Full Text Available Abstract Background Chlamydia trachomatis was previously shown to express a lipoprotein, the macrophage infectivity potentiator (Mip, exposed at the bacterial surface, and able to stimulate human primary monocytes/macrophages through Toll Like Receptor (TLR2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the proinflammatory activity of Mip was significantly higher in the absence than in the presence of serum. The present study aims to investigate the ability of different serum factors to attenuate Mip proinflammatory activity in PMA-differentiated THP-1 cells and in primary human differentiated macrophages. The study was also extend to another lipoprotein, the Borrelia burgdorferi outer surface protein (OspA. The proinflammatory activity was studied through Tumor Necrosis Factor alpha (TNF-α and Interleukin (IL-8 release. Finally, TLR1/2 human embryonic kidney-293 (HEK-293 transfected cells were used to test the ability of the serum factors to inhibit Mip and OspA proinflammatory activity. Results In the absence of any serum and in the presence of 10% delipidated FBS, production of Mip-induced TNF-α and IL-8 in PMA-differentiated THP-1 cells were similar whereas they were significantly decreased in the presence of 10% FBS suggesting an inhibiting role of lipids present in FBS. In the presence of 10% human serum, the concentrations of TNF-α and IL-8 were 2 to 5 times lower than in the presence of 10% FBS suggesting the presence of more potent inhibitor(s in human serum than in FBS. Similar results were obtained in primary human differentiated macrophages. Different lipid components of human serum were then tested (total lipoproteins, HDL, LDL, VLDL, triglyceride emulsion, apolipoprotein (apoA-I, B, E2, and E3. The most efficient inhibitors were LDL, VLDL, and apoB that reduced the mean concentration of TNF-α release in Mip-induced macrophages to 24, 20, and 2%, respectively (p Conclusions These results demonstrated the ability of

Effect of benazepril and pimobendan on serum angiotensin-converting enzyme activity in dogs.

Science.gov (United States)

King, J N; Christinaz, C; Strehlau, G; Hornfeld, J

2018-06-01

To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin-converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel-group design study: A (control, placebo twice daily (BID)); B (0.5-1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25-0.5 mg/kg benazepril BID); D (0.25-0.5 mg/kg benazepril and 0.125-0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25-0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5-1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan. © 2018 John Wiley & Sons Ltd.

Serum bactericidal activity as indicator of innate immunity in pacu Piaractus mesopotamicus (Holmberg, 1887

Directory of Open Access Journals (Sweden)

J.D. Biller-Takahashi

2013-12-01

Full Text Available The immune system of teleost fish has mechanisms responsible for the defense against bacteria through protective proteins in several tissues. The protein action can be evaluated by serum bactericidal activity and this is an important tool to analyze the immune system. Pacu, Piaractus mesopotamicus, is one of the most important fish in national aquaculture. However there is a lack of studies on its immune responses. In order to standardize and assess the accuracy of the serum bactericidal activity assay, fish were briefly challenged with Aeromonas hydrophila and sampled one week after the challenge. The bacterial infection increased the concentration of protective proteins, resulting in a decrease of colony-forming unit values expressed as well as an enhanced serum bactericidal activity. The protocol showed a reliable assay, appropriate to determine the serum bactericidal activity of pacu in the present experimental conditions.

[Tetanus prevention with vaccine and with vaccine plus heterologous immune serum: serum antibody levels in the rabbit].

Science.gov (United States)

Bistoni, F; Mosci, L; Vecchiarelli, A; Marconi, P; Pitzurra, M

1977-01-01

Haemagglutinating antibodies have been assessed in rabbits undergoing active- passive immunization against tetanus. The animals received 6 injections of horse immune serum, 400 UI/kg, and A1PO4 adsorbed toxoid, 0.35 Lf/kg, every 30th day. One the 5th day, after the first injection, E.A. antibodies appeared, at low levels, as a result of a passive immunization. Thereafter the tests became negative, up to the 70th day, when an active immunization emerged, with a 25 days delay in comparison with controls. Neutralization test in vivo behaved in the same way. The results stress once more the need to give up the use of heterologous immune sera in tetanus prophylaxis, in active-passive immunization as well. Arguments adding force to this point of view are: the sensibilization against heterologous proteins, the very low (if any) passive protective action, and, last not least, the delay in the emergence of active immunization: the only reliable shield against tetanus.

Actively paranoid patients with schizophrenia over attribute anger to neutral faces.

Science.gov (United States)

Pinkham, Amy E; Brensinger, Colleen; Kohler, Christian; Gur, Raquel E; Gur, Ruben C

2011-02-01

Previous investigations of the influence of paranoia on facial affect recognition in schizophrenia have been inconclusive as some studies demonstrate better performance for paranoid relative to non-paranoid patients and others show that paranoid patients display greater impairments. These studies have been limited by small sample sizes and inconsistencies in the criteria used to define groups. Here, we utilized an established emotion recognition task and a large sample to examine differential performance in emotion recognition ability between patients who were actively paranoid (AP) and those who were not actively paranoid (NAP). Accuracy and error patterns on the Penn Emotion Recognition test (ER40) were examined in 132 patients (64 NAP and 68 AP). Groups were defined based on the presence of paranoid ideation at the time of testing rather than diagnostic subtype. AP and NAP patients did not differ in overall task accuracy; however, an emotion by group interaction indicated that AP patients were significantly worse than NAP patients at correctly labeling neutral faces. A comparison of error patterns on neutral stimuli revealed that the groups differed only in misattributions of anger expressions, with AP patients being significantly more likely to misidentify a neutral expression as angry. The present findings suggest that paranoia is associated with a tendency to over attribute threat to ambiguous stimuli and also lend support to emerging hypotheses of amygdala hyperactivation as a potential neural mechanism for paranoid ideation. Copyright © 2010 Elsevier B.V. All rights reserved.

Dioxin-like activities in serum across European and Inuit populations

Science.gov (United States)

Long, Manhai; Andersen, Birgitte S; Lindh, Christian H; Hagmar, Lars; Giwercman, Aleksander; Manicardi, Gian-Carlo; Bizzaro, Davide; Spanò, Marcello; Toft, Gunnar; Pedersen, Henning S; Zvyezday, Valentyna; Bonde, Jens Peter; Bonefeld-Jorgensen, Eva C

2006-01-01

Background Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). Methods The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. Results The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. Conclusion No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors. PMID:16725033

Neutralized transport experiment

International Nuclear Information System (INIS)

Roy, P.K.; Yu, S.S.; Eylon, S.; Henestroza, E.; Anders, A.; Gilson, E.P.; Bieniosek, F.M.; Greenway, W.G.; Logan, B.G.; Waldron, W.L.; Shuman, D.B.; Vanecek, D.L.; Welch, D.R.; Rose, D.V.; Thoma, C.; Davidson, R.C.; Efthimion, P.C.; Kaganovich, I.; Sefkow, A.B.; Sharp, W.M.

2005-01-01

Experimental details on providing active neutralization of high brightness ion beam have been demonstrated for Heavy Ion Fusion program. A K + beam was extracted from a variable-perveance injector and transported through 2.4 m long quadrupole lattice for final focusing. Neutralization was provided by a localized cathode arc plasma plug and a RF volume plasma system. Effects of beam perveance, emittance, convergence focusing angle, and axial focusing position on neutralization have been investigated. Good agreement has been observed with theory and experiment throughout the study

The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies

DEFF Research Database (Denmark)

Arendrup, M; Akerblom, L; Heegaard, P M

1995-01-01

The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates...... to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding...... to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding...

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

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Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

2017-12-01

Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

Heterotypic Protection and Induction of a Broad Heterotypic Neutralization Response by Rotavirus-Like Particles

Science.gov (United States)

Crawford, Sue E.; Estes, Mary K.; Ciarlet, Max; Barone, Christopher; O’Neal, Christine M.; Cohen, Jean; Conner, Margaret E.

1999-01-01

The recognition that rotaviruses are the major cause of life-threatening diarrheal disease and significant morbidity in young children has focused efforts on disease prevention and control of these viruses. Although the correlates of protection in children remain unclear, some studies indicate that serotype-specific antibody is important. Based on this premise, current live attenuated reassortant rotavirus vaccines include the four predominant serotypes of virus. We are evaluating subunit rotavirus vaccines, 2/6/7-VLPs and 2/4/6/7-VLPs, that contain only a single VP7 of serotype G1 or G3. In mice immunized parenterally twice, G3 virus-like particles (VLPs) induced a homotypic, whereas G1 VLPs induced a homotypic and heterotypic (G3) serum neutralizing immune response. Administration of three doses of G1 or G3 VLPs induced serum antibodies that neutralized five of seven different serotype test viruses. The inclusion of VP4 in the VLPs was not essential for the induction of heterotypic neutralizing antibody in mice. To confirm these results in another species, rabbits were immunized parenterally with two doses of 2/4/6/7-VLPs containing a G3 or G1 VP7, sequentially with G3 VLPs followed by G1 (G3/G1) VLPs, or with live or psoralen-inactivated SA11. High-titer homotypic serum neutralizing antibody was induced in all rabbits, and low-level heterotypic neutralizing antibody was induced in a subset of rabbits. The rabbits immunized with the G1 or G3/G1 VLPs in QS-21 were challenged orally with live G3 ALA rotavirus. Protection levels were similar in rabbits immunized with homotypic G3 2/4/6/7-VLPs, heterotypic G1 2/4/6/7-VLPs, or G3/G1 2/4/6/7-VLPs. Therefore, G1 2/4/6/7-VLPs can induce protective immunity against a live heterotypic rotavirus challenge in an adjuvant with potential use in humans. Following challenge, broad serum heterotypic neutralizing antibody responses were detected in rabbits parenterally immunized with G1, G3/G1, or G3 VLPs but not with SA11

Serum vaspin levels are associated with physical activity or physical fitness in Japanese: a pilot study.

Science.gov (United States)

Miyatake, Nobuyuki; Wada, Jun; Nakatsuka, Atsuko; Sakano, Noriko; Teshigawara, Sanae; Miyachi, Motohiko; Tabata, Izumi; Numata, Takeyuki

2014-05-01

To investigate the link between serum vaspin levels and physical activity and/or physical fitness in Japanese. A total of 156 subjects (81 men and 75 women) was enrolled in this cross-sectional study. Serum vaspin levels, physical activity by uniaxial accelerometers, peak oxygen uptake, and metabolic risk parameters were evaluated. We also assessed anthropometric and body composition parameters. Serum vaspin levels were over the level of 10 ng/mL in 15 subjects (9.6 %: Vaspin High group). In Vaspin Low group (men and 67 women), serum vaspin levels were 0.12 ± 0.18 ng/mL in men and 0.39 ± 0.70 ng/mL in women. Peak oxygen uptake was significantly and positively correlated with serum vaspin levels even after adjusting for age, physical activity evaluated by Σ[metabolic equivalents × h per week (METs[Symbol: see text]h/w)], BMI, and other confounding factors in men. In turn, physical activity was significantly and positively correlated with serum vaspin levels even after adjusting for confounding factors in women. Serum vaspin levels were closely associated with physical fitness in men and physical activity in women independent of body composition in this Japanese cohort.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

2013-11-15

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

International Nuclear Information System (INIS)

Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

2013-01-01

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

Comparison of a neutralization enzyme immunoassay and an enzyme-linked immunosorbent assay for evaluation of immune status of children vaccinated for mumps.

Science.gov (United States)

Harmsen, T; Jongerius, M C; van der Zwan, C W; Plantinga, A D; Kraaijeveld, C A; Berbers, G A

1992-01-01

A 50% neutralization enzyme immunoassay (N50-EIA) was compared with an indirect enzyme-linked immunosorbent assay (ELISA) for determining mumps virus antibodies in three consecutive serum samples from 138 children vaccinated with a live mumps vaccine at the age (in years) of 1.5. By the N50-EIA, most (132 of 138) preserum samples did not show neutralizing activity. Eight to 12 weeks after vaccination, 17 of the children were still negative, but only 7 remained so after 2.5 years, resulting in a seroconversion rate of 125 of 132 (95%). Over the same period, the neutralization geometric mean titer rose from 3.6 to 9.9. By an indirect ELISA, 128 of 138 preserum samples were found negative. The early and late postvaccination sera of 8 children were ELISA negative, resulting in a seroconversion rate of 120 of 128 (94%). Only two children remained seronegative by both methods. Seven of the late postvaccination serum samples yielded noncorresponding results, reflecting 95% correlation between both methods. Due to cross-reactivity with parainfluenza viruses, the ELISA proved to be less specific, but on the other hand, it showed a greater sensitivity than the N50-EIA. PMID:1500523

Evidence for a modulation of neutral trehalase activity by Ca2+ and cAMP signaling pathways in Saccharomyces cerevisiae

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Souza A.C.

2002-01-01

Full Text Available Saccharomyces cerevisiae neutral trehalase (encoded by NTH1 is regulated by cAMP-dependent protein kinase (PKA and by an endogenous modulator protein. A yeast strain with knockouts of CMK1 and CMK2 genes (cmk1cmk2 and its isogenic control (CMK1CMK2 were used to investigate the role of CaM kinase II in the in vitro activation of neutral trehalase during growth on glucose. In the exponential growth phase, cmk1cmk2 cells exhibited basal trehalase activity and an activation ratio by PKA very similar to that found in CMK1CMK2 cells. At diauxie, even though both cells presented comparable basal trehalase activities, cmk1cmk2 cells showed reduced activation by PKA and lower total trehalase activity when compared to CMK1CMK2 cells. To determine if CaM kinase II regulates NTH1 expression or is involved in post-translational modulation of neutral trehalase activity, NTH1 promoter activity was evaluated using an NTH1-lacZ reporter gene. Similar ß-galactosidase activities were found for CMK1CMK2 and cmk1cmk2 cells, ruling out the role of CaM kinase II in NTH1 expression. Thus, CaM kinase II should act in concert with PKA on the activation of the cryptic form of neutral trehalase. A model for trehalase regulation by CaM kinase II is proposed whereby the target protein for Ca2+/CaM-dependent kinase II phosphorylation is not the neutral trehalase itself. The possible identity of this target protein with the recently identified trehalase-associated protein YLR270Wp is discussed.

Neutralization epitopes on HIV pseudotyped with HTLV-I: Conservation of carbohydrate Epitopes

DEFF Research Database (Denmark)

Sørensen, A M; Nielsen, C; Arendrup, M

1994-01-01

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes

DEFF Research Database (Denmark)

Sørensen, A M; Nielsen, C; Arendrup, M

1994-01-01

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4......-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility...... by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes....

The relationship between serum adiponectin and postpartum luteal activity in high-producing dairy cows.

Science.gov (United States)

Kafi, Mojtaba; Tamadon, Amin; Saeb, Mehdi

2015-05-01

The aims of the present study were to initially determine the pattern of serum adiponectin concentrations during a normal estrous cycle in high-producing postpartum dairy cows and then evaluate the relationship between the serum concentrations of adiponectin and insulin with the commencement of postpartum luteal activity and ovarian activities in clinically healthy high-producing Holstein dairy cows. During a normal estrous cycle of cows (n = 6), serum adiponectin concentrations gradually decreased (P Cows with higher peak of milk yield had lower serum adiponectin concentrations by week 7 postpartum (P = 0.01). Serum adiponectin and insulin concentrations in cows with different postpartum luteal activity (based on the progesterone profile) were evaluated using the following class of cows: normal (≤45 days, n = 11) and delayed (>45 days, n = 11) commencement of luteal activity (C-LA) and four different profiles of normal luteal activity (NLA, n = 5), prolonged luteal phase (n = 6), delayed first ovulation (n = 6), and anovulation (AOV, n = 5). Serum adiponectin concentrations decreased gradually by week 3 postpartum in NLA and then increased; whereas in AOV and delayed first ovulation, they were decreased after week 3 postpartum (P cows was more than that of NLA cows. Insulin concentrations were almost maintained at a stable level in NLA cows (P > 0.05), whereas they increased in the other groups (P cows with C-LA greater than 45 days decreased more than those with C-LA 45 days or less after week 3 postpartum (P = 0.002). Serum adiponectin concentrations at week 7 postpartum were lower in delayed C-LA (P = 0.01). Milk yield in cows with C-LA greater than 45 days increased more than cows with C-LA 45 days or less postpartum (P = 0.002). Insulin concentrations increased relatively in parallel from weeks 1 to 7 postpartum in cows either with C-LA greater than 45 or with C-LA 45 days or less. We showed for the first time the profile of serum adiponectin concentrations

Lower Serum Paraoxonase-1 Activity Is Related to Higher Serum Amyloid A Levels in Metabolic Syndrome

NARCIS (Netherlands)

Kappelle, Paul Jan Willem Herman; Bijzet, Johan; Hazenberg, Bouke Pier; Dullaart, Robin Pieter Frank

Background and Aims. High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally

Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort.

Science.gov (United States)

Wolke, Carmen; Teumer, Alexander; Endlich, Karlhans; Endlich, Nicole; Rettig, Rainer; Stracke, Sylvia; Fiene, Beate; Aymanns, Simone; Felix, Stephan B; Hannemann, Anke; Lendeckel, Uwe

2017-03-01

Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the "Greifswald Approach to Individualized Medicine" (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m 2 or <45 mL/min/1.73 m 2 , respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. Impact statement • Renal and cardiac diseases are very common and often occur concomitantly

MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983-1997

NARCIS (Netherlands)

Müller, Marcel A; Corman, Victor Max; Jores, Joerg; Meyer, Benjamin; Younan, Mario; Liljander, Anne; Bosch, Berend-Jan; Lattwein, Erik; Hilali, Mosaad; Musa, Bakri E; Bornstein, Set; Drosten, Christian

2014-01-01

To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)-seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main

Accelerating the peroxidase-like activity of gold nanoclusters at neutral pH for colorimetric detection of heparin and heparinase activity.

Science.gov (United States)

Hu, Lianzhe; Liao, Hong; Feng, Lingyan; Wang, Min; Fu, Wensheng

2018-04-26

The peroxidase-like catalytic activity of gold nanoclusters (NCs) is quite low around physiological pH, which greatly limits their biological applications. Herein, we found heparin can greatly accelerate the peroxidase-like activity of Au-NCs at neutral pH. The catalytic activity of Au-NCs toward the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2 was 25-fold increased in the presence of heparin at pH 7. The addition of heparin not only accelerated the initial catalytic rate of Au-NCs, but also prevented the Au-NCs from catalyst deactivation. This allows the sensitive colorimetric detection of heparin at neutral pH. In the presence of heparinase, heparin was hydrolyzed into small fragments, weakening the enhancement effect of catalytic activity. Based on this phenomenon, the sensitive colorimetric determination of heparinase in biological samples was also developed.

The activity of neutral DNAase in rat tissue under radiation carcinogenesis

International Nuclear Information System (INIS)

Kerova, N.I.; Pukhova, G.G.; Chebotarev, E.E.

1984-01-01

Activity of a neutral DNA-ase and its natural inhibitor of protein nature in liver, brain and spleen of rats with malignant neoplasms, which have appeared 14-20 months after animal irradiation with fast neutrons in the dose 0.5-1.0 Gy, have been studied. Increase of free DNA-ase activity and its inhibitor with a simultaneous decrease of their ability to complexing in liver and brain supernatants is shoWn. The changes are mostly manifested in liver and in spleen they are inconsiderable and statistically unreliable

Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers.

Science.gov (United States)

Aslan, Mehmet; Duzenli, Ufuk; Esen, Ramazan; Soyoral, Yasemin Usul

2017-10-01

The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; pstress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of measles neutralizing antibody in children under 15 ...

African Journals Online (AJOL)

The immune status of children under 15 years in the Southwestern region of Nigeria against measles virus was determined using the neutralization test with a view to assessing the herd immunity to the virus in these communities. A total of 256 serum samples collected from children were tested by the beta method of ...

Protective levels of canine distemper virus antibody in an urban dog population using plaque reduction neutralization test

Directory of Open Access Journals (Sweden)

O.I. Oyedele

2004-11-01

Full Text Available Blood samples from 50 dogs were collected at three veterinary clinics in Ibadan and Abuja, Nigeria and the serum from each sample was evaluated serologically for neutralizing antibodies against canine distemper virus (CDV by the highly sensitive plaque reduction (PRN neutralization assay. Thirteen dogs had plaque reduction neutralization titres of 0-100, seven had titres of 100-1 000 while 30 had titres ranging from 1 000-6 000. The PRN titres of vaccinated dogs were found to be significantly higher than unvaccinated dogs. The widespread use of the highly reproducible PRN test for the evaluation of antibody response to CDV may be very important in the generation of international CDV positive serum standards that should help to improve pre-and post-vaccination testing of dogs worldwide.

Effect of Physical Activity on Serum Homocysteine Levels in Obese and Overweight Women

Directory of Open Access Journals (Sweden)

R. Soori

2016-09-01

Full Text Available Aims: Recently, homocysteine has been noticed as the major pathogenesis factor of the cardiovascular diseases. The aim of the study was to investigate the effects of physical activities on the serum homocysteine levels, as well as other cardiovascular risk factors in either obese or overweight women. Materials & Methods: In the controlled pretest-posttest semi-experimental study, 18 women referred to the Alzahra sport complexes in districts 3 and 4 of Tehran were studied in 2015. The subjects were selected via random sampling method and randomly divided into two groups; physical activity and control groups. And the intervention program was conducted in the former, while the latter received no intervention. The exercise protocol consisted of 10-week (5 sessions a week stretching exercises and aerobic activities (60 to 75% of the maximum heart beat. The serum homocystein level and lipids were measured both at the start and 48 hours after the exercises. Data was analyzed by SPSS 16 software using paired T and independent T tests. Findings: After the exercises, the mean serum homocysteine level in physical activity group significantly decreased than control group (p=0.001. Nevertheless, the difference between the lipid levels of physical activity and control groups was not significant (p>0.05. Conclusion: Reducing the serum homocysteine concentration, 10-week physical activity might also reduce the risk factors of cardiovascular diseases in either obese or overweight women.

Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome.

Science.gov (United States)

Prencipe, Giusi; Caiello, Ivan; Pascarella, Antonia; Grom, Alexei A; Bracaglia, Claudia; Chatel, Laurence; Ferlin, Walter G; Marasco, Emiliano; Strippoli, Raffaele; de Min, Cristina; De Benedetti, Fabrizio

2018-04-01

The pathogenesis of macrophage activation syndrome (MAS) is not clearly understood: a large body of evidence supports the involvement of mechanisms similar to those implicated in the setting of primary hemophagocytic lymphohistiocytosis. We sought to investigate the pathogenic role of IFN-γ and the therapeutic efficacy of IFN-γ neutralization in an animal model of MAS. We used an MAS model established in mice transgenic for human IL-6 (IL-6TG mice) challenged with LPS (MAS mice). Levels of IFN-γ and IFN-γ-inducible chemokines were evaluated by using real-time PCR in the liver and spleen and by means of ELISA in plasma. IFN-γ neutralization was achieved by using the anti-IFN-γ antibody XMG1.2 in vivo. Mice with MAS showed a significant upregulation of the IFN-γ pathway, as demonstrated by increased mRNA levels of Ifng and higher levels of phospho-signal transducer and activator of transcription 1 in the liver and spleen and increased expression of the IFN-γ-inducible chemokines Cxcl9 and Cxcl10 in the liver and spleen, as well as in plasma. A marked increase in Il12a and Il12b expression was also found in livers and spleens of mice with MAS. In addition, mice with MAS had a significant increase in numbers of liver CD68 + macrophages. Mice with MAS treated with an anti-IFN-γ antibody showed a significant improvement in survival and body weight recovery associated with a significant amelioration of ferritin, fibrinogen, and alanine aminotransferase levels. In mice with MAS, treatment with the anti-IFN-γ antibody significantly decreased circulating levels of CXCL9, CXCL10, and downstream proinflammatory cytokines. The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Serum lysozyme activity in coeliac disease: a possible aid to athe diagnosis of malignant change.

OpenAIRE

Cooper, B T; Ukabam, S O; Barry, R E; Read, A E

1981-01-01

Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.

Microculture Plaque Neutralization Test for California Group Arboviruses

Science.gov (United States)

Seawright, Gary L.; Harding, Gherry; Thomas, Frederick C.; Hanson, Robert P.

1974-01-01

A microculture plaque neutralization test is described for California-group arboviruses that is as precise and quantitative as the standard test conducted in 60-mm petri dishes. It was shown that there was no significant between-panel or between-day variation in determinations and that a single pipette could be used for all serum-dilution levels within a titration without inoculum carry-over effect. The experimental protocol and statistical methods used produce 50% neutralization end points that meet the assumptions of parametric statistics. This permits the power and versatility of the analysis of variance to be exploited in testing for treatment effects in serological and immunological studies with viruses. Images PMID:4216288

Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

Science.gov (United States)

Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

2014-12-01

In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

Relevance of southward magnetic fields in the neutral sheet to anisotropic distribution of energetic electrons and substorm activity

International Nuclear Information System (INIS)

Lui, A.T.Y.; Meng, C.

1979-01-01

The implications of southward magnetic fields at the magnetotail neutral sheet to the development of streaming anisotropy of energetic electrons and magnetospheric substorm activity are examined. Magnetic field and energetic particle measurements from the Imp 6 spacecraft, the AE index, and global auroral images from DMSP spacecraft are utilized in this study. Criteria are developed to identify events of southward magnetic fields at the neutral sheet which imply the presence of X-type magnetic neutral lines. Several features of the observations suggest that the southward magnetic fields and the implied X-type neutral lines are associated with magnetic bubbles in the neutral sheet region. It is found that the signatures of magnetic bubbles are sometimes detected in association with tailward streaming and flux enhancement of energetic electrons (47 keV< E<350keV). A cigar-shaped anisotropy in the energetic electron distribution is frequently but not always observed before the onset of tailward streaming of energetic electrons. The tailward streaming is magnetic field-aligned and occurs in the form of bursts, suggestic electrons. The tailward streaming is magnetic field-aligned and occurs in the form of bursts, suggesting that the generating process is activated somewhat quasi-periodically and is not in a steady state. Signatures of magnetic bubbles are also detected without any substantial enhancement or detectable tailward streaming of energetic electrons. By comparing Imp 6 observations with the AW index and global auroral images from DMSP spacecraft. It is found that signatures of magnetic bubbles in the neutral sheet are observed during substorms as well as during quiet geomagnetic conditions, indicating that magnetic bubbles are intrinsic features of the neutral sheet in the magnetotail regardless of substorm activity

Oral immunization with rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA

International Nuclear Information System (INIS)

Wu Yuzhang; Li Jintao; Mou Zhirong; Fei Lei; Ni Bing; Geng Miao; Jia Zhengcai; Zhou Wei; Zou Liyun; Tang Yan

2003-01-01

Rotaviruses (RV) are a common cause of severe diarrhea in young children, resulting in nearly one million deaths worldwide annually. Rotavirus VP7 was the rotavirus neutralizing protein. Previous study reported that VP7 DNA vaccine can induce high levels of IgG in mice but cannot protect mice against challenge (Choi, A.H., Basu, M., Rae, M.N., McNeal, M.M., Ward, R.L., 1998. Virology 250, 230-240). We found that rotavirus VP7 could maintain its neutralizing immunity when it was transformed into the potato genome. Mice immunized with the transformed tubers successfully elicited serum IgG and mucosal IgA specific for VP7. The mucosal IgA titer was as high as 1000, while serum IgG titer was only 600. Neutralizing assays indicated that IgA could neutralize rotavirus. These results indicate the potential usefulness of plants for production and delivery of edible rotavirus vaccines

THE BACTERICIDAL ACTIVITY OF NORMAL GUINEA PIG SERUM AGAINST LISTERIA MONOCYTOGENES AND ITS INHIBITION BY A LISTERIAL CELL EXTRACT,

Science.gov (United States)

Normal guinea pig serum contains bactericidins active against Listeria monocytogenes. The listeriocidal activity of the serum did not increase after...factor. Lysozyme was not implicated in the bactericidal system. It was suggested that the bactericidal activity of guinea pig serum might be due either to

Search for active-sterile neutrino mixing using neutral-current interactions in NOvA

Science.gov (United States)

Adamson, P.; Aliaga, L.; Ambrose, D.; Anfimov, N.; Antoshkin, A.; Arrieta-Diaz, E.; Augsten, K.; Aurisano, A.; Backhouse, C.; Baird, M.; Bambah, B. A.; Bays, K.; Behera, B.; Bending, S.; Bernstein, R.; Bhatnagar, V.; Bhuyan, B.; Bian, J.; Blackburn, T.; Bolshakova, A.; Bromberg, C.; Brown, J.; Brunetti, G.; Buchanan, N.; Butkevich, A.; Bychkov, V.; Campbell, M.; Catano-Mur, E.; Childress, S.; Choudhary, B. C.; Chowdhury, B.; Coan, T. E.; Coelho, J. A. B.; Colo, M.; Cooper, J.; Corwin, L.; Cremonesi, L.; Cronin-Hennessy, D.; Davies, G. S.; Davies, J. P.; Derwent, P. F.; Dharmapalan, R.; Ding, P.; Djurcic, Z.; Dukes, E. C.; Duyang, H.; Edayath, S.; Ehrlich, R.; Feldman, G. J.; Frank, M. J.; Gabrielyan, M.; Gallagher, H. R.; Germani, S.; Ghosh, T.; Giri, A.; Gomes, R. A.; Goodman, M. C.; Grichine, V.; Groh, M.; Group, R.; Grover, D.; Guo, B.; Habig, A.; Hartnell, J.; Hatcher, R.; Hatzikoutelis, A.; Heller, K.; Himmel, A.; Holin, A.; Howard, B.; Hylen, J.; Jediny, F.; Judah, M.; Kafka, G. K.; Kalra, D.; Kasahara, S. M. S.; Kasetti, S.; Keloth, R.; Kolupaeva, L.; Kotelnikov, S.; Kourbanis, I.; Kreymer, A.; Kumar, A.; Kurbanov, S.; Lackey, T.; Lang, K.; Lee, W. M.; Lin, S.; Lokajicek, M.; Lozier, J.; Luchuk, S.; Maan, K.; Magill, S.; Mann, W. A.; Marshak, M. L.; Matera, K.; Matveev, V.; Méndez, D. P.; Messier, M. D.; Meyer, H.; Miao, T.; Miller, W. H.; Mishra, S. R.; Mohanta, R.; Moren, A.; Mualem, L.; Muether, M.; Mufson, S.; Murphy, R.; Musser, J.; Nelson, J. K.; Nichol, R.; Niner, E.; Norman, A.; Nosek, T.; Oksuzian, Y.; Olshevskiy, A.; Olson, T.; Paley, J.; Patterson, R. B.; Pawloski, G.; Pershey, D.; Petrova, O.; Petti, R.; Phan-Budd, S.; Plunkett, R. K.; Poling, R.; Potukuchi, B.; Principato, C.; Psihas, F.; Radovic, A.; Rameika, R. A.; Rebel, B.; Reed, B.; Rocco, D.; Rojas, P.; Ryabov, V.; Sachdev, K.; Sail, P.; Samoylov, O.; Sanchez, M. C.; Schroeter, R.; Sepulveda-Quiroz, J.; Shanahan, P.; Sheshukov, A.; Singh, J.; Singh, J.; Singh, P.; Singh, V.; Smolik, J.; Solomey, N.; Song, E.; Sousa, A.; Soustruznik, K.; Strait, M.; Suter, L.; Talaga, R. L.; Tas, P.; Thayyullathil, R. B.; Thomas, J.; Tian, X.; Tognini, S. C.; Tripathi, J.; Tsaris, A.; Urheim, J.; Vahle, P.; Vasel, J.; Vinton, L.; Vold, A.; Vrba, T.; Wang, B.; Wetstein, M.; Whittington, D.; Wojcicki, S. G.; Wolcott, J.; Yadav, N.; Yang, S.; Zalesak, J.; Zamorano, B.; Zwaska, R.; NOvA Collaboration

2017-10-01

We report results from the first search for sterile neutrinos mixing with active neutrinos through a reduction in the rate of neutral-current interactions over a baseline of 810 km between the NOvA detectors. Analyzing a 14-kton detector equivalent exposure of 6.05 ×1020 protons-on-target in the NuMI beam at Fermilab, we observe 95 neutral-current candidates at the Far Detector compared with 83.5 ±9.7 (stat ) ±9.4 (syst ) events predicted assuming mixing only occurs between active neutrino species. No evidence for νμ→νs transitions is found. Interpreting these results within a 3 +1 model, we place constraints on the mixing angles θ24<20.8 ° and θ34<31.2 ° at the 90% C.L. for 0.05 eV2≤Δ m412≤0.5 eV2 , the range of mass splittings that produce no significant oscillations over the Near Detector baseline.

Gelatinases A and B activities in the serum of patients with various coronary artery disease stages

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Radenković Sandra

2010-01-01

Full Text Available Background/Aim. The main characteristic of matrix metalloproteinases (MMPs is the degradation of extracellular matrix. Synthesis of MMPs has been reported in coronary atherosclerotic lesions in patients with coronary disease (CD suggesting a pathogenic role of MMPs in its development. Recently there is increasing evidence that gelatinase A (pro MMP-2 and gelatinase B (proMMP-9 play a pathogenic role in the development of the atherosclerotic plaques. The aim of the study was to determine, by the use of a gel image system, a possible presence of active gelatinases in the serum of the patients with CD, as well as if their activity is higher in these patients than in healthy people. Methods. By gelatin zymography we analyzed the activity of proMMP-2 and proMMP-9 in the serum of 50 patients with various coronary artery disease stages and in the serum of 15 healthy controls. The activity was measured by using a gel image system (Kodak Image 1D 3.6.. Results. ProMMP-2 and proMMP-9 activity was significantly higher in the serum of patients with CD compared to controls. There was higher activity of MMP-2 and MMP-9 in the serum of patients with acute myocardial infarction (AMI compared to patients with stable angina pectoris, as well as higher proMMP-9 activity in patients with unstable angina pectoris compared to patients with stable angina pectoris. Conclusion. ProMMP-2 and proMMP-9 participate in processes associated with destabilizing plaques and understanding the processes of MMPs activation and regulation may have significant benefits in clinical interpretation. The reported higher proMMP-2 and proMMP-9 activity in the serum of patients with CD suggests a role of proMMP-2 and proMMP-9 in prognostic stratification of these patients and in designing new drugs.

Continuous recording of long-chain acyl-coenzyme A synthetase activity using fluorescently labeled bovine serum albumin

DEFF Research Database (Denmark)

Demant, Erland J.F.; Nystrøm, Birthe T.

2001-01-01

acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes......acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes...

A Review on Venom Enzymes Neutralizing Ability of Secondary Metabolites from Medicinal Plants

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Pushpendra Singh

2017-09-01

Full Text Available Objectives: Medicinal plants are vital sources of bioactive compounds that are useful for the treatment of patients with snake bites or are indirectly applicable for boosting the effects of conventional serum therapy. These plants are being used traditionally by local healers and tribes for the treatment of patients with snake bites and therefore can be used as an alternative against snake envenomation. Scientifically, using the secondary metabolites of plants to neutralize venom enzymes has an extra benefit of being based on traditional knowledge; also, the use of such metabolites for the treatment of patients with snake bites is cheaper and the treatment can be started sooner. Methods: All the available information on various secondary metabolites exhibiting venom neutralizing ability were collected via electronic search (using Google books, Pubmed, SciFinder, Scirus, Google Scholar, and Web of Science and articles of peer-reviewed journals. Results: Recent interest in different plant has focused on isolating and identifying of different phytoconstituents that exhibit Phospholipase A2 activity and other venom enzyme neutralizing ability. In this support convincing evidence in experimental animal models are available. Conclusion: Secondary metabolites are naturally present, have no side effect, are stable for a long time, can be easily stored, and can neutralize a wide range of snake enzymes, such as phospholipase A2, hyaluronidase, protease, L-amino acid oxidase, 5’nucleotidase, etc. The current review presents a compilation of important plant secondary metabolites that are effective against snake venom due to enzyme neutralization.

The changes in amount and activity of matrix metalloproteinases in rat's serum irradiated by γ-rays

International Nuclear Information System (INIS)

Le Chen; Li Haijun; Cheng Ying; Min Rui

2009-01-01

Rats were whole body irradiated by γ-rays with different doses. A commercial ELISA kit was used to analyze the concentration of MMP-2 and MMP-9 in rat's serum. And Gelatin zymography electrophoresis was used to test the activity of serum MMPs at 24 h after irradiation. The results show that the amount and the activity of MMP-2 in rat's serum increase with increment of irradiation doses. Compared with 1∼4 Gy exposed groups a significant rising of MMP-2 has been found in 5 Gy and 6 Gy exposed groups (p<0.01). On the contrast, the amount and activity of MMP-9 in rat's serum have a little change at 24 hours after irradiation in all of exposed groups. It can be deduced that the changes with amount and activity of MMP-2 may be used as a potential indicator of exposed dose in organisms. (authors)

Interaction of Silver Nanoparticles with Serum Proteins Affects Their Antimicrobial Activity In Vivo

Science.gov (United States)

Gnanadhas, Divya Prakash; Ben Thomas, Midhun; Thomas, Rony; Raichur, Ashok M.

2013-01-01

The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes. PMID:23877702

A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.

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Nicola Clementi

Full Text Available The interest in broad-range anti-influenza A monoclonal antibodies (mAbs has recently been strengthened by the identification of anti-hemagglutinin (HA mAbs endowed with heterosubtypic neutralizing activity to be used in the design of "universal" prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.

Proteolytic activity of IgGs from blood serum of wistar rats at experimental rheumatoid arthritis

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Yu. Ya. Kit

2014-10-01

Full Text Available The aim of this work was to study the proteolytic activity of IgGs purified from blood serum of Wistar rats at experimental rheumatoid arthritis (ERA induced by an injection of bovine collagen of type II. Twenty rats were immunized with a preparation of bovine collagen II (Sigma-Aldrich, USA in the presence of complete Freund’s adjuvant. ERA development was determined by inflammation in limbs of treated animals. IgG preparations were isolated from blood serum of immunized and non-immunized animals by precipitation of antibodies with 33% ammonium sulfate followed by chromatography on the Protein G-Sepharose column. Human histone H1, bovine collagen II, calf thymus histones, myelin basic protein (MBP, bovine serum albumin (BSA, and bovine casein were used as substrates of the proteolytic activity of IgGs. It was found that IgG preparations from blood serum of rats with ERA were capable of cleaving histone H1 and MBP, however, they were catalytically inactive towards collagen II, casein, BSA, and core histones. IgGs from blood serum of non-immunized rats were proteolytically inactive towards all used protein substrates. Thus, we demonstrated that immunization of rats with bovine collagen II induced IgG-antibodies possessing the proteolytic activity towards histone H1 and MBP. This activity might be associated with the development of inflammatory processes in the immunized rats.

Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

Science.gov (United States)

Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

2006-10-01

Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non

Neutralizing activities of caprine antibodies towards conserved regions of the HCV envelope glycoprotein E2

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El-Shenawy Reem

2011-08-01

Full Text Available Abstract Anti HCV vaccine is not currently available and the present antiviral therapies fail to cure approximately half of the treated HCV patients. This study was designed to assess the immunogenic properties of genetically conserved peptides derived from the C-terminal region of HVR-1 and test their neutralizing activities in a step towards developing therapeutic and/or prophylactic immunogens against HCV infection. Antibodies were generated by vaccination of goats with synthetic peptides derived from HCV E2. Viral neutralizing capacity of the generated anti E2 antibodies was tested using in vitro assays. Goats immunized with E2 synthetic peptides termed p412 [a.a 412-419], p430 [a.a 430-447] and p517 [a.a 517-531] generated high titers of antibody responses 2 to 4.5 fold higher than comparable titers of antibodies to the same epitopes in chronic HCV patients. In post infection experiments of native HCV into cultured Huh7.5 cells anti p412 and anti p 517 were proven to be neutralizing to HCV genotype 4a from patients' sera (87.5% and 75% respectively. On the contrary anti p430 exhibited weak viral neutralization capacity on the same samples (31.25%. Furthermore Ab mixes containing anti p430 exhibited reduced viral neutralization properties. From these experiments one could predict that neutralization by Abs towards different E2-epitopes varies considerably and success in the enrichment of neutralization epitope-specific antibodies may be accompanied by favorable results in combating HCV infection. Also, E2 conserved peptides p517 and p412 represent potential components of a candidate peptide vaccine against HCV infection.

Comparing the Effect of Fasting and Physical Activity on Active and Non-active Males’ Body Composition, Serum Osmolarity Levels and Some Parameters of Electrolytes

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M Nematy

2012-08-01

Full Text Available Introduction: Ever since there is insufficient and incoherent information about the effect of the Ramadan Fasting together with regular exercise on levels of serum osmolarity, and electrolytes concentration. The aim of this study was to compare the effect of fasting and physical activity on active and non-active males’ body composition, serum osmolarity levels and some parameters of electrolytes. Methods: Twenty six healthy males, who were selected by convenience sampling method, were divided into two (active and non-active groups. The Active group participated in football training for three sessions per week during the fasting month. All measurements were repeated on the first and last day of fasting month and were used to analyze the test results. Results: The average differences were significantly decreased in weight, BMI, WHR, mineral, total water in two groups (P≤0.05. There was a significant difference in average of BMI, WHR, body fat, mineral and total water between two groups (P≤0.05. Within-group mean differences in glucose, potassium, urine and albumin in both groups were significant (P≤0.05. Differences of serum osmolarity in between- and within-groups were not significant in both groups. While, glucose decreased significantly, the levels of the protein decreased, and urea increased significantly only in non active fasting group. Conclusion: According to these results, regular exercise together with the Ramadan fasting result in change in some serum osmolarity index, electrolytes and water. Therefore, it is necessary to protect the athletics against the malnutrition in Ramadan fasting by using the diet schedule and enough water.

SPE-HPLC purification of endocrine disrupting compounds from human serum for assessment of xenoestrogenic activity

DEFF Research Database (Denmark)

Hjelmborg, P.S.; Ghisari, Mandana; Bonefeld-Jørgensen, Eva

2006-01-01

Assessment of xenoestrogenic activity in human serum samples requires the removal of endogenous sex hormones to assure that the activity measured originates from xenobiotic compounds only. Serum samples representing high, medium and lower accumulation of persistent organic pollutants (POPs) were...... measured by ERE-CALUX was validated and considered to be a valuable tool to assess the combined ER effect of lipophilic serum POPs where additive/synergistic and agonistic/antagonistic effects are integrated giving an overall estimate of exposure and bioactivity....... for the study. MVLN cells, stably transfected with an estrogen receptor (ER) luciferase reporter vector (ERE-CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of the integrated estrogenic activity. The effects of PCBs were analyzed by direct in vitro exposure of PCBs (138, 153...

Trace element analysis of human blood serum by neutron activation analysis

International Nuclear Information System (INIS)

Nakahara, H.; Nagame, Y.; Yoshizawa, Y.; Oda, H.; Gotoh, S.; Murakami, Y.

1979-01-01

An attempt was made to determine if there is any correlation between trace element concentrations in human blood serum and some specific diseases. The serum samples of the patients suffering from cancer, Down syndrome, and Banti syndrome were analyzed by the neutron activation method and compared with the trace element concentrations observed among clinically healthy men. The cancer patients had concentrations in Rb, Mn, Fe, Co, Cu, Zn, Al and Se below normal. The Down syndrome patients were found to have similar deficiencies in Cr, Mn, Fe, Co, Zn, Cu and Sb. (author)

Dioxin-like activities in serum across European and Inuit populations

DEFF Research Database (Denmark)

Long, Manhai; Andersen, Birgitte S; Lindh, Christian H

2006-01-01

Background: Persistent organic pollutants (POPs) such as polychlorinated dibenzo--dioxins/furans, polychlorinatedbiphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals andhumans, many of which involve the aryl hydrocarbon receptor (Ah......,p'-DDE).Methods: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). TheAhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction...

Comparison of neutralizing and hemagglutination-inhibiting antibody responses to influenza A virus vaccination of human immunodeficiency virus-infected individuals

NARCIS (Netherlands)

Benne, CA; Harmsen, M; Tavares, L; Kraaijeveld, CA; De Jong, JC

A neutralization enzyme immunoassay (N-EIA) was used to determine the neutralizing serum antibody titers to influenza A/Taiwan/1/86 (H1N1) and Beijing/353/89 (H3N2) viruses after vaccination of 51 human immunodeficiency virus (HIV) type 1-infected individuals and 10 healthy noninfected controls

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

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M.H. Sonobe

2007-01-01

Full Text Available A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test. In this study, the serum titers (values between 1.0 and 19.5 IU measured by a modified TOBI test (Modi-TOBI test and toxin neutralization assays were correlated (P < 0.0001. Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001 and for diphtheria (r² = 0.93, P < 0.0001 between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

Science.gov (United States)

Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

2012-01-01

Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

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Andrea Marzi

Full Text Available Ebola virus (EBOV is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF. Single monoclonal antibodies (MAbs specific for Zaire ebolavirus (ZEBOV have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226 with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Seasonal disease activity and serum vitamin D levels in rheumatoid ...

African Journals Online (AJOL)

Background: Vitamin D is a steroid hormone that plays essential roles in calcium and phosphorus metabolism, bone formation and mineralization homeostasis, also has a role in the maintenance of immune-homeostasis. Objective: We aimed to investigate seasonal serum vitamin D levels and seasonal disease activity in ...

Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061 by site-directed mutagenesis.

Science.gov (United States)

Xu, Wei; Shao, Rong; Wang, Zupeng; Yan, Xiuhua

2015-03-01

Neutral phytase is used as a feed additive for degradation of anti-nutritional phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its activity. Mutation residues were chosen based on multiple sequence alignments and structure analysis of neutral phytsaes from different microorganisms. The mutation sites on surface (D148E, S197E and N156E) and around the active site (D52E) of phytase were selected. Analysis of the phytase variants showed that the specific activities of mutants D148E and S197E remarkably increased by about 35 and 13% over a temperature range of 40-75 °C at pH 7.0, respectively. The k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild-type phytase, respectively. Both D148E and S197E showed much higher thermostability than that of the wild-type phytase. However, mutants N156E and D52E led to significant loss of specific activity of the enzyme. Structural analysis revealed that these mutations may affect conformation of the active site of phytase. The present mutant phytases D148E and S197E with increased activities and thermostabilities have application potential as additives in aquaculture feed.

Prevalence of neutralizing antibodies to rabies virus in serum of seven species of insectivorous bats from Colorado and New Mexico, United States

Science.gov (United States)

Bowen, Richard A.; O'Shea, Thomas J.; Shankar, Vidya; Neubaum, Melissa A.; Neubaum, Daniel J.; Rupprecht, Charles E.

2013-01-01

We determined the presence of rabies-virus-neutralizing antibodies (RVNA) in serum of 721 insectivorous bats of seven species captured, sampled, and released in Colorado and New Mexico, United States in 2003-2005. A subsample of 160 bats was tested for rabies-virus RNA in saliva. We sampled little brown bats (Myotis lucifugus) at two maternity roosts in Larimer County, Colorado; big brown bats (Eptesicus fuscus) at three maternity roosts in Morgan County, Colorado; and big brown bats at five maternity roosts in Larimer County. We also sampled hoary bats (Lasiurus cinereus) and silver-haired bats (Lasionycteris noctivagans) captured while drinking or foraging over water in Bernalillo County, New Mexico and at various locations in Larimer County. Big brown bats, little brown bats, long-legged myotis (Myotis volans), long-eared myotis (Myotis evotis), and fringed myotis (Myotis thysanodes) were also sampled over water in Larimer County. All species except long-eared myotis included individuals with RVNA, with prevalences ranging from 7% in adult female silver-haired bats to 32% in adult female hoary bats. None of the bats had detectable rabies-virus RNA in oropharyngeal swabs, including 51 bats of 5 species that had RVNA in serum. Antibody-positive bats were present in nine of the 10 maternity colonies sampled. These data suggest that wild bats are commonly exposed to rabies virus and develop a humoral immune response suggesting some degree of viral replication, but many infections fail to progress to clinical disease.

Neutralization of lethality and proteolytic activities of Malayan pit viper (Calloselasma rhodostoma) venom with North American Virginia opossum (Didelphis virginiana) serum.

Science.gov (United States)

Pornmanee, Piboon; Sánchez, Elda E; López, Gonzalo; Petsom, Amorn; Khow, Orawan; Pakmanee, Narumol; Chanhome, Lawan; Sangvanich, Polkit; Pérez, John C

2008-07-01

Malayan pit viper (Calloselasma rhodostoma) envenomation is a major health problem in South East Asia. During envenomation, venom components mainly affect the hemostatic system. The sera from the North American Virginia opossums (Didelphis virginiana) were able to neutralize the venom of the Malayan pit viper. These natural inhibitors could be explored as potential therapeutics against envenomations of a variety of venomous snake species in different geographical habitats.

Immunoreactive somatomedin A in human serum

International Nuclear Information System (INIS)

Hall, K.; Brandt, J.; Enberg, G.; Fryklund, L.

1979-01-01

A RIA has been developed for somatomedin A (SM-A) utilizing Sepharose-bound antibodies. This assay, measuring SM-A, the insulin-like growth factors 1 and 2, and somatomedin C, allows determination in serum samples. In comparison with a serum standard, the mean serum levels in patients with acromegaly or GH deficiency and healthy subjects were 8.7 +- 0.7 (n=25), 0.24 +- 0.02 (n=25), and 1.15 +- 0.11 U/ml, respectively. The correlation coefficient between immunoreactive SM-A and SM-A by radioreceptor assay was highly significant (r=0.93), although the potency ratio of SM-A between the two groups of patients was higher in the RIA than in the radioreceptor assay. Gel chromatography revealed that SM-A in acromegalic serum is bound to a carrier protein which is absent in patients with GH deficiency. After gel chromatography at low pH, 90% of applied immunoreactive SM-A was recovered in the low molecular weight fraction and consisted mainly of neutral polypeptides

Enhanced static ground power unit based on flying capacitor based h-bridge hybrid active-neutral-point-clamped converter

DEFF Research Database (Denmark)

Abarzadeh, Mostafa; Madadi Kojabadi, Hossein; Deng, Fujin

2016-01-01

Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages of the p......Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages...

Influenza virus neutralizing antibodies and IgG isotype profiles after immunization of mice with influenza A subunit vaccine using various adjuvants

NARCIS (Netherlands)

Benne, CA; Harmsen, M; vanderGraaff, W; Verheul, AFM; Snippe, H; Kraaijeveld, CA

The influence of various adjuvants on the development of influenza virus neutralizing antibodies and distribution of anti-influenza virus IgG isotypes after immunization of mice with influenza A (H3N2) subunit vaccine was investigated. Serum titres of influenza virus neutralizing antibodies and

Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.

Directory of Open Access Journals (Sweden)

Weiyan Huang

Full Text Available Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5 mg/ml- 10(-1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.

Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

Science.gov (United States)

Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

2014-01-01

Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

Science.gov (United States)

Baran, A; Świderska, M; Myśliwiec, H; Flisiak, I

2017-03-01

Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

Directory of Open Access Journals (Sweden)

Maryam Boshtam

2013-01-01

Full Text Available Introduction. Cardioprotective effect of high density lipoprotein (HDL is, in part, dependent on its related enzyme, paraoxonase 1 (PON1. Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA. PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

Serum paraoxonase 1 activity is associated with fatty acid composition of high density lipoprotein.

Science.gov (United States)

Boshtam, Maryam; Razavi, Amirnader Emami; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

2013-01-01

Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω 6 fatty acids of HDL. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

Science.gov (United States)

Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

2016-01-01

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

Cloning of the first human anti-JCPyV/VP1 neutralizing monoclonal antibody: epitope definition and implications in risk stratification of patients under natalizumab therapy.

Science.gov (United States)

Diotti, Roberta Antonia; Mancini, Nicasio; Clementi, Nicola; Sautto, Giuseppe; Moreno, Guisella Janett; Criscuolo, Elena; Cappelletti, Francesca; Man, Petr; Forest, Eric; Remy, Louise; Giannecchini, Simone; Clementi, Massimo; Burioni, Roberto

2014-08-01

JC virus (JCPyV) has gained novel clinical importance as cause of progressive multifocal leukoencephalopathy (PML), a rare demyelinating disease recently associated to immunomodulatory drugs, such as natalizumab used in multiple sclerosis (MS) cases. Little is known about the mechanisms leading to PML, and this makes the need of PML risk stratification among natalizumab-treated patients very compelling. Clinical and laboratory-based risk-stratification markers have been proposed, one of these is represented by the JCPyV-seropositive status, which includes about 54% of MS patients. We recently proposed to investigate the possible protective role of neutralizing humoral immune response in preventing JCPyV reactivation. In this proof-of-concept study, by cloning the first human monoclonal antibody (GRE1) directed against a neutralizing epitope on JCPyV/VP1, we optimized a robust anti-JCPyV neutralization assay. This allowed us to evaluate the neutralizing activity in JCPyV-positive sera from MS patients, demonstrating the lack of correlation between the level of anti-JCPyV antibody and anti-JCPyV neutralizing activity. Relevant consequences may derive from future clinical studies induced by these findings; indeed the study of the serum anti-JCPyV neutralizing activity could allow not only a better risk stratification of the patients during natalizumab treatment, but also a better understanding of the pathophysiological mechanisms leading to PML, highlighting the contribution of peripheral versus central nervous system JCPyV reactivation. Noteworthy, the availability of GRE1 could allow the design of novel immunoprophylactic strategies during the immunomodulatory treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

OpenAIRE

Eklund, A; Blaschke, E

1986-01-01

The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of al...

Mechanism of anti-HIV activity of succinylated human serum albumin

NARCIS (Netherlands)

Kuipers, ME; Berg, HVD; Swart, PJ; Laman, Jon; Meijer, DKF; Kopelman, MHGM; Huisman, H

1999-01-01

In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and

Increased serum YKL-40 in patients with pulmonary sarcoidosis—a potential marker of disease activity?

DEFF Research Database (Denmark)

Johansen, JS; Milman, N; Hansen, M

2005-01-01

macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. Methods: Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological...

Activity and stability trends of perovskite oxides for oxygen evolution catalysis at neutral pH

OpenAIRE

Ling, Chen; Jia, Hongfei; Han, Binghong; Risch, Marcel; Lee, Yueh Lin; Shao-Horn, Yang

2015-01-01

Perovskite oxides (ABO[subscript 3]) have been studied extensively to promote the kinetics of the oxygen evolution reaction (OER) in alkaline electrolytes. However, developing highly active catalysts for OER at near-neutral pH is desirable for many photoelectrochemical/electrochemical devices. In this paper, we systematically studied the activity and stability of well-known perovskite oxides for OER at pH 7. Previous activity descriptors established for perovskite oxides at pH 13, such as hav...

Significance of determination of serum cytidine deaminase (CD) levels for diagnosis of active rheumatoid arthritis (RA)

International Nuclear Information System (INIS)

Xiao Chuangqing; Jang Xiaogong; He Yunnan

2005-01-01

Objective: To determine the clinical value of measurement of serum cytidine deaminase (CD) levels in patients with active rheumatoid arthritis (RA). Methods: Serum levels of CD were detected with spectrophotometry, in 33 patients with active RA and 60 controls. The erythrocyte sedimentation rate (ESR) and CRP content were also determined in both groups. Results: The ser- um CD contents in patients with active RA(14.80 ± 2.11U/ml) were significantly higher than those in controls(4.86±1.86 U/ml,P<0.01). The CRP contents (51.46 ± 20.43mg/L) and ESR readings(85.03 ± 27.6mm/h) in the patients were also significantly higher than those in the controls(3.40 ± 2.21mg/L and 13.04 ± 4.89mm/h respectively, all P<0.01). In the patients, the serum CD contents were linearly positively correlated with the ESR contents and CRP readings (r=0.6324 and 0.8013 respectively, P <0.01). Conclusion: Serum CD is an early biochemical marker for diagnosis of active rheumatoid arthritis and is also of prognostic value. (authors)

Are "Market Neutral" Hedge Funds Really Market Neutral?

OpenAIRE

Andrew J. Patton

2009-01-01

Using a variety of different definitions of "neutrality," this study presents significant evidence against the neutrality to market risk of hedge funds in a range of style categories. I generalize standard definitions of "market neutrality," and propose five different neutrality concepts. I suggest statistical tests for each neutrality concept, and apply these tests to a database of monthly returns on 1423 hedge funds from five style categories. For the "market neutral" style, approximately o...

Spectroscopic studies on the interaction and sonodynamic damage of neutral red (NR) to bovine serum albumin (BSA)

Energy Technology Data Exchange (ETDEWEB)

Liu Bin; Guo Ying [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Jun, E-mail: wangjun890@126.co [Department of Chemistry, Liaoning University, Shenyang 110036 (China); Xu Rui [Department of Chemistry, Liaoning University, Shenyang 110036 (China); Wang Xin; Wang Dan; Zhang Liqun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Xu Yongnan [Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016 (China)

2010-06-15

In this paper, the interaction of neutral red (NR) with bovine serum albumin (BSA) and the sonodynamic damage to BSA under ultrasonic irradiation was studied by means of ultraviolet-visible (UV-vis) and fluorescence spectra. The quenching constant (K{sub SV}=5.749x10{sup 4} L/mol), binding constant (K{sub A}=3.19x10{sup 4} L/mol) and binding site number (n=0.9462) were measured. The binding distance (r=2.47 nm) between NR and BSA was obtained according to Foester's non-radiative energy transfer theory. The damage process of BSA molecules was detected by the hyperchromic effect of UV-vis spectra and quenching of intrinsic fluorescence spectra. In addition, the influencing factors such as ultrasonic irradiation time and NR concentration on the damage to BSA molecules were also considered. The results showed that the damage degree is enhanced with the increase of ultrasonic irradiation time and NR concentration. The possible mechanism of sonodynamic damage to BSA molecules was mainly mediated by singlet oxygen ({sup 1}O{sub 2}). Otherwise, the binding and damaging sites to BSA molecules were also estimated by synchronous fluorescence. The results indicated that the NR is more vicinal to tryptophan (Trp) residue than to tyrosine (Tyr) residue and the damage site is also mainly at Trp residues. The research result will bring a certain significance to use sonosensitive drugs in the fields of tumor treatment.

Serum diamine oxidase activity in patients with histamine intolerance.

Science.gov (United States)

Manzotti, G; Breda, D; Di Gioacchino, M; Burastero, S E

2016-03-01

Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. We found that 10 out of 14 patients had serum DAO activityintolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031). In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy. © The Author(s) 2015.

Determination of mercury in human serum and packed blood cells by neutron activation analysis

International Nuclear Information System (INIS)

Versieck, J.; Vanballenberghe, L.; Wittoek, A.; Vermeir, G.; Vandecasteele, C.

1990-01-01

A method is described for the determination of mercury in human blood serum and packed blood cells employing neutron activation analysis. Great attention was devoted to the collection and manipulation of the samples. The accuracy and precision of the method were tested by analyzing biological reference materials and by comparing the concentrations measured in a number of serum samples to those obtained by another, independent technique (cold vapor atomic absorption spectrometry) in the same samples. The article reports the levels measured in blood serum and packed blood cells samples from 15 adult volunteers, as well as the figures determined in a open-quotes second-generationclose quotes biological reference material (freeze-dried human serum), prepared and conditioned at the University of Ghent

Sodium ions activated phosphofructokinase leading to enhanced D-lactic acid production by Sporolactobacillus inulinus using sodium hydroxide as a neutralizing agent.

Science.gov (United States)

Zheng, Lu; Liu, Mingqing; Sun, Jiaduo; Wu, Bin; He, Bingfang

2017-05-01

Sporolactobacillus inulinus is a superior D-lactic acid-producing bacterium and proposed species for industrial production. The major pathway for D-lactic acid biosynthesis, glycolysis, is mainly regulated via the two irreversible steps catalyzed by the allosteric enzymes, phosphofructokinase (PFK) and pyruvate kinase. The activity level of PFK was significantly consistent with the cell growth and D-lactic acid production, indicating its vital role in control and regulation of glycolysis. In this study, the ATP-dependent PFK from S. inulinus was expressed in Escherichia coli and purified to homogeneity. The PFK was allosterically activated by both GDP and ADP and inhibited by phosphoenolpyruvate; the addition of activators could partly relieve the inhibition by phosphoenolpyruvate. Furthermore, monovalent cations could enhance the activity, and Na + was the most efficient one. Considering this kind activation, NaOH was investigated as the neutralizer instead of the traditional neutralizer CaCO 3 . In the early growth stage, the significant accelerated glucose consumption was achieved in the NaOH case probably for the enhanced activity of Na + -activated PFK. Using NaOH as the neutralizer at pH 6.5, the fermentation time was greatly shortened about 22 h; simultaneously, the glucose consumption rate and the D-lactic acid productivity were increased by 34 and 17%, respectively. This probably contributed to the increased pH and Na + -promoted activity of PFK. Thus, fermentations by S. inulinus using the NaOH neutralizer provide a green and highly efficient D-lactic acid production with easy subsequent purification.

18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis

Directory of Open Access Journals (Sweden)

Anne E.D. Arraes

Full Text Available ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG uptake on positron emission tomography–computed tomography (PET–CT and serum levels of different cytokines and matrix metalloproteinases (MMPs in patients with Takayasu arteritis (TA and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α, interleukin (IL-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001. Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001. Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049 while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046. Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042. By receiver operating characteristic (ROC curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039. Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045 and controls (p = 0.012. Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001. No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.

Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in patients with rheumatoid arthritis--TOMORROW study.

Science.gov (United States)

Matsumoto, Yoshinari; Sugioka, Yuko; Tada, Masahiro; Okano, Tadashi; Mamoto, Kenji; Inui, Kentaro; Habu, Daiki; Koike, Tatsuya

2015-03-01

The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level. A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay. Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate. Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.

[Serum calcium and phosphorus concentration and alkaline phosphatase activity in healthy children during growth and development].

Science.gov (United States)

Savić, Ljiljana; Savić, Dejan

2008-01-01

Many changes happen during growth and development in an organism as a result of important hormon changes, especially biohumoral ones. These changes make a problem when interpreting biochemical results in pediatric population. The most important changes are intensive calcium and phosphorus metabolic turnover in bone tissue with changes in alkaline phosphatase activity as a result of osteoblast activity. The aim of this study was to follow the serum calcium and phosphorus concentration and alkaline phosphatase activity in children 1-15 years old in different growth and development period and of different sexes and to fortify the influence of growth and development dynamics on biohumoral status in healthy male and female children. We evaluated 117 healthy children of both sexes from 1-15 years of age and divided them into three age groups: 1-5, 6-10 and 11-15 years. We followed the serum calcium and phosphorus concentration and alkaline phosphatase activity in different groups and in different sexes. Our investigation found significantly higher values of serum calcium in boys than in girls with no important changes between the age groups and significantly higher values of serum phosphorus in the youngest age group in all children and in different sexes with no important sex differences. Alkaline phosphatase activity followed the growth spurt and was the biggest in 6-10 years group in girls and in 11-15 years group in boys.

The neural fate of neutral information in emotion-enhanced memory.

Science.gov (United States)

Watts, Sarah; Buratto, Luciano G; Brotherhood, Emilie V; Barnacle, Gemma E; Schaefer, Alexandre

2014-07-01

In this study, we report evidence that neural activity reflecting the encoding of emotionally neutral information in memory is reduced when neutral and emotional stimuli are intermixed during encoding. Specifically, participants studied emotional and neutral pictures organized in mixed lists (in which emotional and neutral pictures were intermixed) or in pure lists (only-neutral or only-emotional pictures) and performed a recall test. To estimate encoding efficiency, we used the Dm effect, measured with event-related potentials. Recall for neutral items was lower in mixed compared to pure lists and posterior Dm activity for neutral items was reduced in mixed lists, whereas it remained robust in pure lists. These findings might be caused by an asymmetrical competition for attentional and working memory resources between emotional and neutral information, which could be a major determinant of emotional memory effects. Copyright © 2014 Society for Psychophysiological Research.

Optimization and validation of a neutralizing antibody assay for HIV-1 in A3R5 cells.

Science.gov (United States)

Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju; Todd, Christopher A; Bilska, Miroslawa; Martelli, Amanda; LaBranche, Celia; Perez, Lautaro G; Ochsenbauer, Christina; Kappes, John C; Rountree, Wes; Denny, Thomas N; Montefiori, David C

2014-07-01

A3R5 is a human CD4(+) lymphoblastoid cell line that was engineered to express CCR5 and is useful for the detection of weak neutralizing antibody responses against tier 2 strains of HIV-1. Here we describe the optimization and validation of the HIV-1 neutralizing antibody assay that utilizes A3R5 cells, performed in compliance with Good Clinical Laboratory Practice (GCLP) guidelines. The assay utilizes Renilla luciferase-expressing replication competent infectious molecular clones (IMC) encoding heterologous env genes from different HIV-1 clades. Key assay validation parameters tested included specificity, accuracy, precision, limit of detection and quantitation, specificity, linearity and range, and robustness. Plasma samples demonstrated higher non-specific activity than serum samples in the A3R5 assay. This assay can tolerate a wide range of virus input but is more sensitive to cell concentration. The higher sensitivity of the A3R5 assay in neutralization responses to tier 2 strains of HIV-1 makes it complementary to, but not a substitute for the TZM-bl assay. The validated A3R5 assay is employed as an endpoint immunogenicity test for vaccine-elicited neutralizing antibodies against tier 2 strains of HIV-1, and to identify correlates of protection in HIV-1 vaccine trials conducted globally. Copyright © 2014 Elsevier B.V. All rights reserved.

Relationship between elevated serum gamma-glutamyltransferase activity and slow coronary flow

DEFF Research Database (Denmark)

Sen, Nihat; Ozlü, Mehmet F; Basar, Nurcan

2009-01-01

OBJECTIVES: We evaluated the relationship between coronary blood flow and serum gamma-glutamyltransferase (GGT) activity in patients with slow coronary flow (SCF). STUDY DESIGN: The study included 90 patients (47 men, 43 women; mean age 50.8+/-9.4 years) with SCF and 88 patients (45 men, 43 women...

Effect of citric acid and microbial phytase on serum enzyme activities ...

African Journals Online (AJOL)

Effect of citric acid and microbial phytase on serum enzyme activities and plasma minerals retention in broiler chicks. ... African Journal of Biotechnology ... An experiment was conducted to study the effect of microbial phytase supplementation and citric acid in broiler chicks fed corn-soybean meal base diets on enzyme ...

Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and Predictive Biomarker in Pancreatic Cancer.

Science.gov (United States)

Felix, Klaus; Hinz, Ulf; Dobiasch, Sophie; Hackert, Thilo; Bergmann, Frank; Neumüller, Magnus; Gronowitz, Simon; Bergqvist, Mattias; Strobel, Oliver

2018-01-01

The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC). Using the sensitive TK activity assay DiviTum, preoperative serum samples from 404 PDAC, 28 chronic pancreatitis, and 25 autoimmune pancreatitis patients and 83 healthy volunteers were analyzed. The preoperative S-TK activities of 54 PDAC patients who received neoadjuvant therapy (nTx) were also compared with those of 258 PDAC patients who did not receive nTx. The preoperative S-TK activities of PDAC patients were significantly higher and discriminatory from autoimmune and chronic pancreatitis patients and control groups. The S-TK activity in PDAC patients was associated with overall survival. Patients with S-TK activity of less than 80 Du (DiviTum units)/L demonstrated median survival of 20.3 months with an estimated 18.0% 5-year survival rate; for S-TK activity of 80 Du/L or greater, median survival was 15.1 months with a 6.8% 5-year survival rate. For early-stage PDAC, these differences were even more pronounced. The S-TK activity in the nTx group was significantly higher than that in the group not receiving nTx. Pancreatic ductal adenocarcinomas reveal a significant increase in S-TK activity, which is associated with overall survival, especially in early tumor stages. Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy.

Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

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Denicar Lina Nascimento Fabris Maeda

2017-09-01

Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

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Nicolas O. Jørgensen

2018-04-01

Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

DEFF Research Database (Denmark)

Moghimi, S.M.; Hamad, I.; Bunger, R.

2006-01-01

level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed......Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum...

Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification.

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Vallance, Hilary; Morris, Tara J; Coulter-Mackie, Marion; Lim-Steele, Joyce; Kaback, Michael

2006-02-01

A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated.

NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

International Nuclear Information System (INIS)

Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

2013-01-01

During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O 3 per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H 2 O 2 ) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H 2 O 2 are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment

NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

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Pecorelli, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Child Neuropsychiatry Unit, University Hospital, AOUS, Siena (Italy); Bocci, Velio [Department of Physiology, University of Siena (Italy); Acquaviva, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Belmonte, Giuseppe [Department of Biomedical Sciences, University of Siena (Italy); Gardi, Concetta [Department of Molecular and Developmental Medicine, University of Siena (Italy); Virgili, Fabio [INRAN, Rome (Italy); Ciccoli, Lucia [Department of Molecular and Developmental Medicine, University of Siena (Italy); Valacchi, Giuseppe, E-mail: giuseppe.valacchi@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara (Italy); Department of Food and Nutrition, Kyung Hee University, Seoul (Korea, Republic of)

2013-02-15

During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

Relationship between serum adiponectin level and ATPase activity of erythrocyte membrance in patients with 2-type diabetes

International Nuclear Information System (INIS)

Song Jiejin

2008-01-01

Objective: To explore the possible mechanism of development nephrosis as related to changes of serum adiponectin levels and alteration of activities of Na + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase of erythrocyte membrance in patients with 2-type diabetes. Methods: Serum adiponectin levels (with RIA) and erythrocyte membrance (prepared with Reilnila method) Na + ·K + - ATPase and Ca +2 ·Mg +2 -ATPase activity were determined in 45 DM2 patients without nephropathy, 31 DM2 patients with nephropathy and 30 controls. Results: Serum adiponectin levels in the diabetic patients were significantly lower than those in controls (P + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase activities were also significantly lower than those in controls (P + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase activities of erythrocyte membrance. (authors)

Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

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Manetta J

2014-08-01

Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

Design of multi-megawatt actively cooled beam dumps for the Neutral-Beam Engineering Test Facility

International Nuclear Information System (INIS)

Paterson, J.A.; Koehler, G.; Wells, R.P.

1981-10-01

The Neutral Beam Engineering Test Facility will test Neutral Beam Sources up to 170 keV, 65 Amps, with 30 second beam-on times. For this application actively cooled beam dumps for both the neutral and ionized particles will be required. The dumps will be able to dissipate a wide range of power density profiles by utilizing a standard modular panel design which is incorporated into a moveable support structure. The thermal hydraulic design of the panels permit the dissipation of 2 kW/cm 2 anywhere on the panel surface. The water requirements of the dumps are optimized by restricting the flow to panel sections where the heat flux falls short of the design value. The mechanical design of the beam-dump structures is described along with tests performed on a prototype panel. The prototype tests were performed on two different panel designs, one manufactured by Mc Donnell Douglas (MDAC) the other by United Technologies (UT). The dissipation capabilities of the panels were tested at the critical regions to verify their use in the beam dump assemblies

Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

International Nuclear Information System (INIS)

Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

2005-01-01

Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

Relationship between serum leptin levels, ATPase activity of erythrocyte membrance and development of diabetic nephropathy in patients with DM2

International Nuclear Information System (INIS)

Wang Yuming

2009-01-01

Objective: To study the possible mechanism of development of nephrosis affected by changes of serum leptin levels and alteration of activities of Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase of erythrocyte membrane in patients with type 2 diabetes(DM2). Methods: Serum leptin levels (with RIA) and erythrocyte membrane Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase activitities (with Reinila method) were determined in 40 DM2 patients without nephropathy, 32 DM2 patients with nephropathy and 35 controls. Results Serum leptin levels were significantly higher in the diabetics as a whole than those in controls (P + K + -ATPase and Ca 2+ Mg 2+ -ATPase activities were significantly lower (P<0.01). Among the diabetic patients, the serum leptin levels in patients without nephrosis (P<0.05), but the RBC membrance ATPase activities were significantly lower(P<0.05). Conclusion: Development of type 2 diabetes nephrosis might be correlated with the high serum leptin level and decreased ATPase activities of erythrocite membrane. (authors)

Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

Science.gov (United States)

Bajnok, L; Seres, I; Varga, Z; Jeges, S; Peti, A; Karanyi, Z; Juhasz, A; Csongradi, E; Mezosi, E; Nagy, E V; Paragh, G

2008-11-01

The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, Pcorrelated positively with PON1 (r=0.24, PHDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

The effect on serum myeloperoxidase activity and oxidative status of eradication treatment in patients Helicobacter pylori infected.

Science.gov (United States)

Nazligul, Yaşar; Aslan, Mehmet; Horoz, Mehmet; Celik, Yilmaz; Dulger, Ahmet Cumhur; Celik, Hakim; Erel, Ozcan

2011-06-01

Myeloperoxidase activity has been investigated after eradication of Helicobacter pylori (H. pylori) in infected patients in previous studies but the results are controversial. The aim of this study was to investigate effect on serum myeloperoxidase activity and oxidative status of eradication treatment in H. pylori-infected patients. Gastric biopsy specimens were obtained from 30 H. pylori infected patients. Serum myeloperoxidase activity was measured by enzyme-linked immunoassay. Oxidative status was determined using total antioxidant capacity (TAC) and total oxidant status (TOS) measurement and calculation of oxidative stress index (OSI). After 2 weeks of the eradication treatment, serum myeloperoxidase activity, TOS and OSI values were significantly lower (all; p<0.001), while TAC was significantly higher (p<0.001). Our results indicate that eradication treatment in H. pylori-infected patients may affect both oxidative stress and myeloperoxidase activity which is an important biomarker in pathogenesis of atherosclerosis. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effect of copper intrauterine device vs. injectable contraceptive on serum hormone levels and cell mitotic activity in endometrium

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Ebtesam Moustafa Kamal

2013-09-01

Conclusion: Either copper intrauterine device or injectable contraceptive usage for more than 9 months results in significant decrease in endometrial proliferative or cell mitotic activity. While copper IUD has no effect on serum estradiol or progesterone levels, DMPA usage increased serum progesterone level with no effect on serum estradiol.

Individual contributions of the human metapneumovirus F, G, and SH surface glycoproteins to the induction of neutralizing antibodies and protective immunity

International Nuclear Information System (INIS)

Skiadopoulos, Mario H.; Biacchesi, Stephane; Buchholz, Ursula J.; Amaro-Carambot, Emerito; Surman, Sonja R.; Collins, Peter L.; Murphy, Brian R.

2006-01-01

We evaluated the individual contributions of the three surface glycoproteins of human metapneumovirus (HMPV), namely the fusion F, attachment G, and small hydrophobic SH proteins, to the induction of serum HMPV-binding antibodies, serum HMPV-neutralizing antibodies, and protective immunity. Using reverse genetics, each HMPV protein was expressed individually from an added gene in recombinant human parainfluenza virus type 1 (rHPIV1) and used to infect hamsters once or twice by the intranasal route. The F protein was highly immunogenic and protective, whereas G and SH were only weakly or negligibly immunogenic and protective, respectively. Thus, in contrast to other paramyxoviruses, the HMPV attachment G protein is not a major neutralization or protective antigen. Also, although the SH protein of HMPV is a virion protein that is much larger than its counterparts in previously studied paramyxoviruses, it does not appear to be a significant neutralization or protective antigen

Bleaching of Neutral Cotton Seed Oil Using Organic Activated Carbon in a Batch System: Kinetics and Adsorption Isotherms

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Abba Chetima

2018-03-01

Full Text Available In the processing of cotton and neem seeds to obtain oil for diverse uses, enormous quantities of seed husk are generated as waste, which when not properly disposed of, poses environmental problems. One way of reducing this waste is to use it for the production of activated carbon (AC for its multiple applications. In this work, activated carbon was produced from cotton and neem seed husks by carbonization followed by acid activation. The prepared ACs were characterized for its porosity and surface properties as well as for its ability to bleach neutral cotton seed oil. The prepared ACs are very efficient in the decoloration process, as they removed about 96–98% of the pigments compared to 98.4% removal with commercial bleaching earth. Temperature had a pronounced effect on the bleaching of neutral cotton seed oil. Maximum adsorption was observed at 60 °C for a contact time of 45 min. The adsorption kinetics were modelled by the intra-particle and the pseudo-second order equations while the adsorption isotherms followed the Langmuir and Freundlich equations. It is concluded that the organic ACs are efficient in pigment removal from neutral cotton seed oil and therefore are potential bleaching agents for the vegetable oil industry.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

Science.gov (United States)

Zhang, Chen-Xing; Cai, Li; Shao, Kang; Wu, Jing; Zhou, Wei; Cao, Lan-Fang; Chen, Tong-Xin

2018-05-01

Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1β, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Use of Pavo cristatus feather extract for the better management of snakebites: neutralization of inflammatory reactions.

Science.gov (United States)

Murari, Satish K; Frey, Felix J; Frey, Brigitte M; Gowda, There V; Vishwanath, Bannikuppe S

2005-06-03

In Indian traditional medicine, peacock feather in the form of ash (Bhasma) or water extract are used against snakebite and to treat various problems associated with lungs. This study was aimed to evaluate the water extract of peacock feather (PCF) against the local tissue damage caused due to snakebite. PCF water extract showed inhibition towards phospholipase A2 enzyme activity from snake venom (Naja naja and Vipera russelii), inflammatory fluids (synovial, pleural, ascites) and normal serum in a dose-dependent manner. Hyaluronidase and proteases are other major enzymes in snake venoms responsible for local tissue damage. PCF water extract inhibited hyaluronidase and proteolytic enzyme activities from Vipera russelii, Naja naja and Trimeresurus malabaricus venom. The active principle is a hydrophilic molecule easily extractable in water or polar solvents. PCF water extract gave positive results for the presence of protein and secondary metabolites like carotenoids and steroids. Analysis of metal ions revealed that iron is the major ion (> 20-fold). Other metal ions detected in smaller amount are copper, chromium, zinc and nickel. The least amount of ion detected is gold. Co-injection of PCF water extract with snake venom and inflammatory PLA2 enzymes neutralize the edema inducing activity of all the PLA2 enzymes studied. Since it inhibits hyaluronidase and proteases enzyme activity from snake venom PCF water extract is a powerful neutralizing agent, which has therapeutic application against venom toxicity.

Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

Energy Technology Data Exchange (ETDEWEB)

Lau, Aik Jiang; Chang, Thomas K.H., E-mail: thomas.chang@ubc.ca

2014-06-01

The naturally occurring SV23 splice variant of human constitutive androstane receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is detected as a contaminant in fetal bovine serum (FBS). In our initial experiment, we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR-SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type of FBS (regular > dialyzed > CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS, but not regular FBS or dialyzed FBS, was used. With increasing concentrations (1–10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly increased (CS-FBS). Subsequent experiments identified a serum-free culture condition to detect DEHP activation of hCAR-SV23. Under this condition, artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they decreased it in cells cultured in medium supplemented with 10% regular FBS. By comparison, FBS increased the basal activity of the wild-type isoform of hCAR (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion, FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in cell-based assays, but investigations on functional ligands of hCAR isoforms can be conducted in serum-free culture condition. - Highlights: • FBS leads to erroneous pharmacological classification of hCAR-SV23 ligands. • Artemisinin, artemether, and arteether activate h

Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes.

Science.gov (United States)

Dukić, Lora; Simundić, Ana-Maria; Malogorski, Davorin

2014-01-01

Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = -0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration.

Differential neutralizing activities of a single domain camelid antibody (VHH specific for ricin toxin's binding subunit (RTB.

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Cristina Herrera

Full Text Available Ricin, a member of the A-B family of ribosome-inactivating proteins, is classified as a Select Toxin by the Centers for Disease Control and Prevention because of its potential use as a biothreat agent. In an effort to engineer therapeutics for ricin, we recently produced a collection of alpaca-derived, heavy-chain only antibody VH domains (VHH or "nanobody" specific for ricin's enzymatic (RTA and binding (RTB subunits. We reported that one particular RTB-specific VHH, RTB-B7, when covalently linked via a peptide spacer to different RTA-specific VHHs, resulted in heterodimers like VHH D10/B7 that were capable of passively protecting mice against a lethal dose challenge with ricin. However, RTB-B7 itself, when mixed with ricin at a 1 ∶ 10 toxin:antibody ratio did not afford any protection in vivo, even though it had demonstrable toxin-neutralizing activity in vitro. To better define the specific attributes of antibodies associated with ricin neutralization in vitro and in vivo, we undertook a more thorough characterization of RTB-B7. We report that RTB-B7, even at 100-fold molar excess (toxin:antibody was unable to alter the toxicity of ricin in a mouse model. On the other hand, in two well-established cytotoxicity assays, RTB-B7 neutralized ricin with a 50% inhibitory concentration (IC50 that was equivalent to that of 24B11, a well-characterized and potent RTB-specific murine monoclonal antibody. In fact, RTB-B7 and 24B11 were virtually identical when compared across a series of in vitro assays, including adherence to and neutralization of ricin after the toxin was pre-bound to cell surface receptors. RTB-B7 differed from both 24B11 and VHH D10/B7 in that it was relatively less effective at blocking ricin attachment to receptors on host cells and was not able to form high molecular weight toxin:antibody complexes in solution. Whether either of these activities is important in ricin toxin neutralizing activity in vivo remains to be determined.

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

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Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

2009-05-01

Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy.

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Ash, Daniel B; Papadimitriou, Dimitra; Hays, Arthur P; Dimauro, Salvatore; Hirano, Michio

2012-09-01

Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy. To report the clinical and molecular features of a case of neutral lipid storage disease with myopathy resulting from a novel mutation in PNPLA2. Case report. University hospital. A 65-year-old man with progressive muscle weakness and high serum creatine kinase levels. Direct sequencing of the PNPLA2 gene. Identification of a novel homozygous mutation in the patient's PNPLA2 gene confirmed the suspected diagnosis of neutral lipid storage disease with myopathy. Screening of the PNPLA2 gene should be considered for patients presenting with high levels of creatine kinase, progressive muscle weakness, and systemic lipid accumulation. The presence of Jordans anomaly can be a strong diagnostic clue.

Low Serum Paraoxonase-1 Lactonase and Arylesterase Activities in Obese Children and Adolescents

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Sandor Raluca

2015-12-01

Full Text Available Serum paraoxonase-1 (PON1 binds mainly to high density lipoproteins (HDLs and protects low density lipoproteins (LDLs against oxidation. While paraoxonase and arylesterase activities are traditionally assayed, lactonase activity, accounting for protection against LDL oxidation, was less investigated in obese children and adolescents. Therefore, we aimed to measure lactonase, paraoxonase and arylesterase activities, oxidized LDL (ox-LDL and malondialdehyde (MDA levels in obese children and adolescents.

Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

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Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

2011-02-01

Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.

Heavy neutral leptons at FASER

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Kling, Felix; Trojanowski, Sebastian

2018-05-01

We study the prospects for discovering heavy neutral leptons at Forward Search Experiment (FASER), the newly proposed detector at the LHC. Previous studies showed that a relatively small detector with ˜10 m length and ≲1 m2 cross sectional area can probe large unconstrained parts of parameter space for dark photons and dark Higgs bosons. In this work, we show that FASER will also be sensitive to heavy neutral leptons that have mixing angles with the active neutrinos that are up to an order of magnitude lower than current bounds. In particular, this is true for heavy neutral leptons produced dominantly in B -meson decays, in which case FASER's discovery potential is comparable to the proposed SHiP detector. We also illustrate how the search for heavy neutral leptons at FASER will be complementary to ongoing searches in high-pT experiments at the LHC and can shed light on the nature of dark matter and the process of baryogenesis in the early Universe.

On becoming neutral: effects of experimental neutralizing reconsidered.

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van den Hout, M; van Pol, M; Peters, M

2001-12-01

Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier.

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

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Manzi Susan

2011-01-01

Full Text Available Abstract Background Low serum paraoxonase (PON activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE. Our prior studies have shown that the PON1/rs662 (p.Gln192Arg, PON1/rs854560 (p.Leu55Met, PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample. Methods PON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP or TaqMan allelic discrimination methods. Results Our pair-wise linkage disequilibrium (LD analysis, using an r2 cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys, rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183 and immunologic disorder (rs11981433 in SLE patients (P = 0.013 to 0.042. Conclusions Our data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.

Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

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Jianhua Sui

2008-11-01

Full Text Available Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S protein of animal and human SARS coronaviruses (SARS-CoVs during and between two zoonotic transfers (2002/03 and 2003/04 are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID "hot spot" in a light chain CDR (complementarity determining region alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural

Neutral Theory and Scale-Free Neural Dynamics

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Martinello, Matteo; Hidalgo, Jorge; Maritan, Amos; di Santo, Serena; Plenz, Dietmar; Muñoz, Miguel A.

2017-10-01

Neural tissues have been consistently observed to be spontaneously active and to generate highly variable (scale-free distributed) outbursts of activity in vivo and in vitro. Understanding whether these heterogeneous patterns of activity stem from the underlying neural dynamics operating at the edge of a phase transition is a fascinating possibility, as criticality has been argued to entail many possible important functional advantages in biological computing systems. Here, we employ a well-accepted model for neural dynamics to elucidate an alternative scenario in which diverse neuronal avalanches, obeying scaling, can coexist simultaneously, even if the network operates in a regime far from the edge of any phase transition. We show that perturbations to the system state unfold dynamically according to a "neutral drift" (i.e., guided only by stochasticity) with respect to the background of endogenous spontaneous activity, and that such a neutral dynamics—akin to neutral theories of population genetics and of biogeography—implies marginal propagation of perturbations and scale-free distributed causal avalanches. We argue that causal information, not easily accessible to experiments, is essential to elucidate the nature and statistics of neural avalanches, and that neutral dynamics is likely to play an important role in the cortex functioning. We discuss the implications of these findings to design new empirical approaches to shed further light on how the brain processes and stores information.

New Insight into the Hydrogen Evolution Reaction under Buffered Near-Neutral pH Conditions: Enthalpy and Entropy of Activation

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Shinagawa, Tatsuya

2016-10-06

Electrochemical conversion of thermodynamically stable chemicals of water and carbon dioxide is regarded as a core technology for achieving sustainability in our society. In both cases, the electrochemical hydrogen evolution reaction (HER) is a key reaction, particularly at near-neutral pH. This study addresses the kinetic aspects of the HER in buffered near-neutral pH conditions using a variety of electrode materials (W, Ni, Pt, Au, and Cu) over a wide temperature range (299–346 K). When the overall performance was summarized with respect to the binding energy of the reaction intermediate species, a classic volcano-shaped relationship was obtained. Interestingly, the temperature sensitivity analysis disclosed that smaller activation energies did not always lead to higher performance in 1.5 mol L–1 K-phosphate solution (pH 5.8). Detailed analysis of the temperature- and potential-dependent parameters revealed that smaller activation energies coincided with smaller values of the pre-exponential factor in the Arrhenius’ equation (associated with the entropy of activation). Due to the trade-off relationship of enthalpy–entropy compensation in the current system, the conventional approach of mixing elements of lower and higher binding energies to the intermediate species failed: even though Ni–Cu showed lower apparent activation energy, its activity toward the HER was between that of Ni and Cu due to the lowered entropy of activation. This study demonstrates the unrevealed fundamental aspects of the HER in buffered near-neutral condition, which contributes to the rational development of efficient energy and material conversion systems.

Loss Distribution Analysis of Three-Level Active Neutral-Point-Clamped (3L-ANPC) Converter with Different PWM Strategies

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Zhang, Gang; Yang, Yongheng; Iannuzzo, Francesco

2016-01-01

The three-level (3L) Active Neutral-Point-Clamped (ANPC) topology has been introduced to resolve the uneven loss distribution issue in the classical 3L Neutral-Point-Clamped (NPC) topology. This Pulse-Width-Modulation (PWM) strategy is then an important means to fully explore the potential benefits...... are separated in order to improve the loss distribution among the power devices. A comparison between the proposed strategy and other major PWM strategies for the loss distribution is also carried out in this paper. Benchmarking results show that the proposed strategy has effective and superior performance...

Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model.

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An, Li-Sha; Yuan, Xiao-Hua; Hu, Ying; Shi, Zi-Yun; Liu, Xiao-Qin; Qin, Li; Wu, Gui-Qing; Han, Wei; Wang, Ya-Qin; Ma, Xu

2012-11-01

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Serum thymidine kinase activity of various cancer and HBV positive liver diseases

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Torizumi, Kazutami; Aibata, Hirofumi; Kiji, Shigeyuki; Ohta, Kiichiro; Okamoto, Yukiharu; Ohshiro, Iwao; Hirose, Tetsuhito

1987-03-01

Clinical utility of determination of serum deoxythymidine kinase (TK) activity is described. It is well known that elevated TK level is observed in leukemia and other malignant diseases, or some viral infectious diseases. The TK activity was assayed on normal subjects, hepatitis B virus (HBV) positive liver diseases and various cancer by a newly developed high sensitive method, radioenzyme assay (REA) utilizing /sup 125/I-iododeoxyuridine as the substrate. Measurement of TK activity by the REA is revealed to be useful for ''the marker of DNA metabolism anomaly'' in leukemia, etc.

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

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Dursun, Polat; Demirtaş, Ezgi; Bayrak, Ahmet; Yarali, Hakan

2006-01-01

Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

Milk minerals modify the effect of fat intake on serum lipid profile

DEFF Research Database (Denmark)

Lorenzen, Janne Kunchel; Jensen, Søren Krogh; Astrup, Arne

2014-01-01

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid...

Evaluation of smallpox vaccines using variola neutralization.

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Damon, Inger K; Davidson, Whitni B; Hughes, Christine M; Olson, Victoria A; Smith, Scott K; Holman, Robert C; Frey, Sharon E; Newman, Frances; Belshe, Robert B; Yan, Lihan; Karem, Kevin

2009-08-01

The search for a 'third'-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific 'in vitro' activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.

The Myth of Neutral Judge: Overcoming Neutrality by the Cognition Theory And the Pursuit of Legal Certainty

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Alyane Almeida de Araújo

2016-11-01

Full Text Available The  Law  scientific-rational  character  created  the  image  of  a  neutral  judge;  however, Neuroscience currently shows that the decision-making process involves activations in the prefrontal cortex along with emotions management areas. The aim of this work is to check the subsistence of the neutral judge after the cognition theory, with points of reflexion in post- positivist hermeneutics. Using the comprehensive method on bibliographic prospection, we conclude that despite the neutrality has been overcome, the search for legal certainty continues, which will be achieved through values and social purposes of the onwn normative system.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

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Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

DEFF Research Database (Denmark)

Johansen, Julia S; Milman, Nils; Hansen, Michael

2005-01-01

YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant...... cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity....

Holotoxin A1 Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral Sphingomyelinase in K562 and Human Primary Leukemia Cells

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Seong-Hoon Yun

2018-04-01

Full Text Available Marine triterpene glycosides are attractive candidates for the development of anticancer agents. Holotoxin A1 is a triterpene glycoside found in the edible sea cucumber, Apostichopus (Stichopus japonicus. We previously showed that cladoloside C2, the 25(26-dihydro derivative of holotoxin A1, induced apoptosis in human leukemia cells by activating ceramide synthase 6. Thus, we hypothesized that holotoxin A1, which is structurally similar to cladoloside C2, might induce apoptosis in human leukemia cells through the same molecular mechanism. In this paper, we compared holotoxin A1 and cladoloside C2 for killing potency and mechanism of action. We found that holotoxin A1 induced apoptosis more potently than cladoloside C2. Moreover, holotoxin A1 induced apoptosis in K562 cells by activating caspase-8 and caspase-3, but not by activating caspase-9. During holotoxin A1-induced apoptosis, acid sphingomyelinase (SMase and neutral SMase were activated in both K562 cells and human primary leukemia cells. Specifically inhibiting acid SMase and neutral SMаse with chemical inhibitors or siRNAs significantly inhibited holotoxin A1–induced apoptosis. These results indicated that holotoxin A1 might induce apoptosis by activating acid SMase and neutral SMase. In conclusion, holotoxin A1 represents a potential anticancer agent for treating leukemia. Moreover, the aglycone structure of marine triterpene glycosides might affect the mechanism involved in inducing apoptosis.

Effect of an obesogenic diet on circadian activity and serum hormones in old monkeys

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Henryk F Urbanski

2017-07-01

Full Text Available Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD. Old female rhesus macaques were ovo-hysterectomized (OvH to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E, beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS. These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

Correlation of serum paraoxonase activities in known cases of 130 elderly hypertensive South Asian aged 56-64 years - a hospital based study

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Arun Kumar

2014-02-01

Full Text Available Objective: To evaluate paraoxonase activity, antioxidant status and lipid peroxidation in hypertensive participants and to address the hypothesis that oxidative modifications of lipids due to hypertension can cause changes in serum paraoxonase activities. Methods: The serum paraoxonase activities, antioxidants and lipid peroxidation were determined in 130 hypertensive participants and 130 age-sexes matched normotensive healthy volunteers served as control. Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity were determined by standard methods. Malondialdehyde was measured by thiobarbituric acid reaction. Conjugated diene level was measured by Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin, serum ascorbic acid and lipid profile were analyzed by standard methods. Results: Total cholesterol, triglycerides, low-density lipoprotein cholesterol were significantly higher and high-density lipoprotein cholesterol were significantly lower in hypertensive patients when compared to normotensive healthy controls. The superoxide dismutase, glutathione peroxidase and catalase were significantly lower in hypertensive when compared with normotensive. Similar findings were observed in the levels of albumin, uric acid, bilirubin and ascorbic acid when hypertensives were compared with normotensive. The oxidative stress indicators namely malondialdehyde and conjugated diene were significantly higher and paraoxonase activity were significantly lower in hypertensive. Conclusions: Our study concludes that paraoxonase activities are bound to alter in hypertension which is caused due to interplay of several confounding factors namely oxidative stress, increased oxidized low-density lipoprotein and depletion of antioxidants.

NON-NEUTRALIZED ELECTRIC CURRENT PATTERNS IN SOLAR ACTIVE REGIONS: ORIGIN OF THE SHEAR-GENERATING LORENTZ FORCE

International Nuclear Information System (INIS)

Georgoulis, Manolis K.; Titov, Viacheslav S.; Mikić, Zoran

2012-01-01

Using solar vector magnetograms of the highest available spatial resolution and signal-to-noise ratio, we perform a detailed study of electric current patterns in two solar active regions (ARs): a flaring/eruptive and a flare-quiet one. We aim to determine whether ARs inject non-neutralized (net) electric currents in the solar atmosphere, responding to a debate initiated nearly two decades ago that remains inconclusive. We find that well-formed, intense magnetic polarity inversion lines (PILs) within ARs are the only photospheric magnetic structures that support significant net current. More intense PILs seem to imply stronger non-neutralized current patterns per polarity. This finding revises previous works that claim frequent injections of intense non-neutralized currents by most ARs appearing in the solar disk but also works that altogether rule out injection of non-neutralized currents. In agreement with previous studies, we also find that magnetically isolated ARs remain globally current-balanced. In addition, we confirm and quantify the preference of a given magnetic polarity to follow a given sense of electric currents, indicating a dominant sense of twist in ARs. This coherence effect is more pronounced in more compact ARs with stronger PILs and must be of sub-photospheric origin. Our results yield a natural explanation of the Lorentz force, invariably generating velocity and magnetic shear along strong PILs, thus setting a physical context for the observed pre-eruption evolution in solar ARs.

Effects of neutral phytase on growth performance and phosphorus utilization in crucian carp (Carassius auratus).

Science.gov (United States)

Nie, Xin-Zheng; Chen, Sha; Zhang, Xiao-Xu; Dai, Bin-Yang; Qian, Li-Chun

A feeding trial was conducted for nine weeks to investigate the effects of partially replacing Ca(H 2 PO 4 ) 2 with neutral phytase on the growth performance, phosphorus utilization, nutrient digestibility, serum biochemical parameters, bone and carcass mineral composition, and digestive-enzyme-specific activity in crucian carp (Carassius auratus). The diets prepared with 0.8%, 0%, and 1.8% Ca(H 2 PO 4 ) 2 (1%=1 g/100 g) supplements were regarded as the P 1 E 0 , negative control (NC), and positive control (PC) groups, respectively; the other three experimental diets were prepared with the addition of 200, 300, and 500 U/kg of neutral phytase, respectively, based on the P 1 E 0 group. Three hundred and eighty-four fish ((1.50±0.01) g) were randomly distributed in the six treatments with four replicates each. The fish were initially fed with 2%-3% diets of their body weight per day, with feeding twice daily (08:00 and 16:00), under a 12-h light/12-h dark cycle at the temperature of (27.56±0.89) °C. The results showed that supplemental phytase at different levels in the diet improved the final body weight, average daily gain, feed conversion ratio, phosphorus utilization, and protein efficiency ratio of crucian carp (PPhytase supplementation increased the mineral content in serum (P), bone (P, Ca), and carcass (P, Ca, Zn, Na, and Mg) (Pphytase-supplemented diets (Pphytase improved the growth performance, phosphorus utilization as well as nutrient utilization in crucian carp, and it can be considered an important nutritional replacement for Ca(H 2 PO 4 ) 2 .

Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

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Ellsworth, J.L.; Brown, C.; Cooper, A.D.

1988-01-01

The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies.

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Anette H Draborg

Full Text Available In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs in systemic lupus erythematosus (SLE patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs' association with Epstein-Barr virus (EBV antibodies was examined.Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance.Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001 also after adjusting for Ig levels (p<0.0001. The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI score of the SLE patients (r = 0.399, p = 0.007. Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009, and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation whereas EBV-directed antibodies reflect the extent of previous infection/reactivations.SLE patients have elevated concentrations of serum FLCs that correlate with global disease

High serum ACE activity predicts severe hypoglycaemia over time in patients with type 1 diabetes

DEFF Research Database (Denmark)

Færch, Louise; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2011-01-01

High serum angiotensin-converting enzyme (ACE) activity is associated with increased risk of severe hypoglycaemia (SH) within 1 year in type 1 diabetes. We wanted to find out whether ACE activity is stable over time and predicts SH beyond 1 year, and if gender differences exist in the association...

Clinical significance of the changes of serum levels of the rheumatoid activity markers IL-2, sIL-2R, HA and VEGF

International Nuclear Information System (INIS)

Bao Yong; Long Wubin; Yu Ke; Zeng Ying; Liu Deying

2004-01-01

Objective: To explore the relationship between rheumatoid activity and serum levels of the cytokines interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), hyaluronic acid (HA), vascular endothelial growth factor (VEGF) in patients with rheumatoid arthritis. Methods: Serum IL-2, HA(with RIA) and sIL-2R, VEGF (with ELISA) levels were determined in 30 controls, 30 patients with active rheumatoid arthritis and 30 patients with rheumatoid arthritis in remission. Sensitivity and specificity for each marker were analyzed. Results: In patients with active rheumatoid arthritis, the serum levels of sIL-2R, HA, VEGF were significantly higher and serum levels of IL-2 significantly lower than those in patients in remission and controls (p<0.01). Determination of VEGF levels possessed the highest specificity (93.3%) and also a high sensitivity (93.3% as well). Conclusion: Determination of the serum levels of any of these markers was valuable for monitoring the activity of the rheumatoid process. It is more desirable to take measurements of VEGF levels due to its highest specificity

Regulation of IgE antibody production by serum molecules. II. Strain-specificity of the suppressive activity of serum from complete Freund's adjuvant-immune low responder mouse donors

International Nuclear Information System (INIS)

Katz, D.H.; Tung, A.S.

1978-01-01

IgE antibody production in mice of high and low IgE responder phenotypes, respectively, can be appreciably enhanced in magnitude after low-dose whole-body x irradiation. Such enhanced responses, as well as adoptive secondary IgE responses, can be markedly suppressed by passive transfer of CFA-immune serum in low responder strains, but not in high responder strains. The studies presented here demonstrate that the suppressive activity of CFA-immune serum on IgE antibody production is strain specific. This is true even in reciprocal combinations of low IgE responder SJL and C57BL/6 mice, in which it was shown that serum capable of suppressing mice of the isologous strain was ineffective in diminishing IgE antibody production in the other low responder strain. Absence of suppressive activity in CFA-immune sera obtained from H-2 haplotypes while sharing many similarities in the background genome and, conversely, effective suppressive activity of H-2 congenic donor sera when H-2-identities between donor and recipient mice existed, strongly suggested a role, at least in part, of H-2 genes in dictating the strain specificity of such suppressive activity. Additional experiments provided evidence for a possible role of macrophages in catabolism of the active molecules in CFA-immune sera. These observations, together with those presented in the preceding paper, may provide valuable insight toward successful development of appropriate manipulations that could ultimately convert high IgE responder individuals into low responders

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies.

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Chervyakova, Olga V; Zaitsev, Valentin L; Iskakov, Bulat K; Tailakova, Elmira T; Strochkov, Vitaliy M; Sultankulova, Kulyaisan T; Sandybayev, Nurlan T; Stanbekova, Gulshan E; Beisenov, Daniyar K; Abduraimov, Yergali O; Mambetaliyev, Muratbay; Sansyzbay, Abylay R; Kovalskaya, Natalia Y; Nemchinov, Lev G; Hammond, Rosemarie W

2016-06-07

The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae) structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV) strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122), orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins.

Recombinant Sheep Pox Virus Proteins Elicit Neutralizing Antibodies

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Olga V. Chervyakova

2016-06-01

Full Text Available The aim of this work was to evaluate the immunogenicity and neutralizing activity of sheep pox virus (SPPV; genus Capripoxvirus, family Poxviridae structural proteins as candidate subunit vaccines to control sheep pox disease. SPPV structural proteins were identified by sequence homology with proteins of vaccinia virus (VACV strain Copenhagen. Four SPPV proteins (SPPV-ORF 060, SPPV-ORF 095, SPPV-ORF 117, and SPPV-ORF 122, orthologs of immunodominant L1, A4, A27, and A33 VACV proteins, respectively, were produced in Escherichia coli. Western blot analysis revealed the antigenic and immunogenic properties of SPPV-060, SPPV-095, SPPV-117 and SPPV-122 proteins when injected with adjuvant into experimental rabbits. Virus-neutralizing activity against SPPV in lamb kidney cell culture was detected for polyclonal antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins. To our knowledge, this is the first report demonstrating the virus-neutralizing activities of antisera raised to SPPV-060, SPPV-117, and SPPV-122 proteins.

Study on the growth promoting capacity of calf and fetal bovine serum for animal cells "in vitro" II: electrophoretic study and survey on the antiproteolytic activity of pools of calf and fetal bovine serum

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Edda de Rizzo

1984-04-01

Full Text Available Calf serum and fetal bovine serum present great variability as to its growth promoting efficiency (GPE. As supplement of culture media to cultivate cells of animal origin they stimulate the "in vitro" multiplication and maintain cell viability. When fourteen lots of calf sera of variable GPE had the total protein contents as well as the percentages of serum fractions determined, no significant differences that could possibly explain the variability of the GPE were observed. Evaluation of the antiproteolytic activity of nineteen lots of calf serum and eighteen serum lots of younger calves showed that the former exhibited lower antiproteolytic titers (1:40 to 1:80 than the latter (1:80 to 1:160. Twelve lots of fetal bovine serum studied in parallel, showed the highest concentration of antiproteolytic factors, with titers equal to 1:320. Sera of bovine origin, but not fetal sera, are usually heat-inactivated, what was demonstrated to be responsible for the decrease of the antiproteolytic activity of 75% of the lots tested. This could explain the inability of certain heat-inactivated sera in promoting multiplication of some cells "in vitro", as verified with primary monkey kidney cells. The results obtained in this study indicated the convenience of submiting each lot of serum to be introduced in cell culture to previous determination of its characteristics, such as growth promoting efficiency, antiproteolytic activity and also toxicity, absence of extraneous agents, etc., in order to minimize the possibility of using serum lots of questionable quality, thus preventing not only the loss of cell lines, but also undesirable and sometimes expensive delays.

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

International Nuclear Information System (INIS)

Bates, John T.; Keefer, Christopher J.; Slaughter, James C.; Kulp, Daniel W.; Schief, William R.; Crowe, James E.

2014-01-01

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K on ) for binding to RSV F protein, while alteration of dissociation rate (K off ) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K on with reduced potency mirrored the effect of increased K on found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K on ) correlated well with the potency of neutralization

Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein

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Bates, John T. [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Keefer, Christopher J. [The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Slaughter, James C. [The Vanderbilt Vaccine Center, Departments of Biostatistics and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); Kulp, Daniel W. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Schief, William R. [IAVI Neutralizing Antibody Center and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA (United States); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA (United States); Crowe, James E., E-mail: james.crowe@vanderbilt.edu [The Vanderbilt Vaccine Center, Departments of Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States); The Vanderbilt Vaccine Center, Departments of Pediatrics, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN (United States)

2014-04-15

The role of binding kinetics in determining neutralizing potency for antiviral antibodies is poorly understood. While it is believed that increased steady-state affinity correlates positively with increased virus-neutralizing activity, the relationship between association or dissociation rate and neutralization potency is unclear. We investigated the effect of naturally-occurring antibody resistance mutations in the RSV F protein on the kinetics of binding to palivizumab. Escape from palivizumab-mediated neutralization of RSV occurred with reduced association rate (K{sub on}) for binding to RSV F protein, while alteration of dissociation rate (K{sub off}) did not significantly affect neutralizing activity. Interestingly, linkage of reduced K{sub on} with reduced potency mirrored the effect of increased K{sub on} found in a high-affinity enhanced potency palivizumab variant (motavizumab). These data suggest that association rate is the dominant factor driving neutralization potency for antibodies to RSV F protein antigenic site A and determines the potency of antibody somatic variants or efficiency of escape of viral glycoprotein variants. - Highlights: • The relationship of affinity to neutralization for virus antibodies is uncertain. • Palivizumab binds to RSV escape mutant fusion proteins, but with reduced affinity. • Association rate (K{sub on}) correlated well with the potency of neutralization.

Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions.

Science.gov (United States)

Rodak, L; Babiuk, L A; Acres, S D

1982-07-01

The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.

Preferential amygdala reactivity to the negative assessment of neutral faces.

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Blasi, Giuseppe; Hariri, Ahmad R; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R; Mattay, Venkata S

2009-11-01

Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues.

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

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Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients.

Science.gov (United States)

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

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Yunoki M

2016-07-01

Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords

Decreased Killing Activity of Micafungin Against Candida guilliermondii, Candida lusitaniae, and Candida kefyr in the Presence of Human Serum.

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Saleh, Qasem; Kovács, Renátó; Kardos, Gábor; Gesztelyi, Rudolf; Kardos, Tamás; Bozó, Aliz; Majoros, László

2017-09-01

Currently, echinocandins are first-line drugs for treatment of invasive candidiasis. However, data on how serum influences killing activity of echinocandins against uncommon Candida species are limited. Therefore, the killing activity of micafungin in RPMI-1640 and in 50% serum was compared against Candida guilliermondii, Candida lusitaniae, and Candida kefyr. Minimum inhibitory concentration (MIC) ranges in RPMI-1640 were 0.5-1, 0.12-0.25, and 0.06-0.12 mg/L, respectively. In 50% serum, MICs increased 32- to 256-fold. In RPMI-1640 ≥ 0.25, ≥4, and 32 mg/L micafungin was fungicidal against all four C. kefyr (≤4.04 hours), two of three C. lusitaniae (≤16.10 hours), and two of three C. guilliermondii (≤12.30 hours), respectively. In 50% serum, all three species grew at ≤4 mg/L. Micafungin at 16-32 mg/L was fungicidal against all C. kefyr isolates (≤3.03 hours) and at 32 mg/L was fungistatic against one of three C. lusitaniae isolates. Two C. lusitaniae isolates and all three C. guilliermondii grew at all tested concentrations. Adding human serum to susceptibility test media drew attention to loss of fungicidal or fungistatic activity of micafungin in the presence of serum proteins, which is not predicted by MICs in case of C. kefyr and C. lusitaniae in RPMI-1640. Our results strongly suggest that micafungin and probably other echinocandins should be used with caution against rare Candida species.

The potential for using slags activated with near neutral salts as immobilisation matrices for nuclear wastes containing reactive metals

Science.gov (United States)

Bai, Y.; Collier, N. C.; Milestone, N. B.; Yang, C. H.

2011-06-01

The UK currently uses composite blends of Portland cement and other inorganic cementitious material such as blastfurnace slag and pulverised fuel ash to encapsulate or immobilise intermediate and low level radioactive wastes. Typically levels up 9:1 blast furnace slag:Portland cement or 4:1 pulverised fuel ash:Portland cement are used. Whilst these systems offer many advantages, their high pH causes corrosion of various metallic intermediate level radioactive wastes. To address this issue, lower pH/weakly alkaline cementitious systems have to be explored. While the blast furnace slag:Portland cement system is referred to as a composite cement system, the underlying reaction is actually an indirect activation of the slag hydration by the calcium hydroxide generated by the cement hydration, and by the alkali ions and gypsum present in the cement. However, the slag also can be activated directly with activators, creating a system known as alkali-activated slag. Whilst these activators used are usually strongly alkaline, weakly alkaline and near neutral salts can also be used. In this paper, the potential for using weakly alkaline and near neutral salts to activate slag in this manner is reviewed and discussed, with particular emphasis placed on the immobilisation of reactive metallic nuclear wastes.

The detection of hemorrhagic proteins in snake venoms using monoclonal antibodies against Virginia opossum (Didelphis virginiana) serum.

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Sánchez, E E; García, C; Pérez, J C; De La Zerda, S J

1998-10-01

Most snakes and a few warm-blooded animals have a resistance to snake venoms because of naturally occurring antihemorrhagins found in their sera. The antihemorrhagins in serum of Virginia opossum (Didelphis virginiana) neutralize hemorrhagic activity by binding to hemorrhagins in snake venoms. The binding characteristic of antihemorrhagins in D. virginiana serum was used to develop a five-step western blot. The detection of hemorrhagic proteins were measured indirectly with antihemorrhagins in Virginia opossum serum and with DV-2LD#2, a monoclonal antibody specific for Virginia opossum antihemorrhagins. Snake venoms were separated by native-PAGE, transferred to a Millipore Immobilon-P membrane and then incubated with crude Virginia opossum serum. The hemorrhagins in snake venom bind to antihemorrhagins in Virginia opossum serum which react with DV-2LD#2 a monoclonal antibody that is specific for Virginia opossum antihemorrhagins. DV-2LD#2 monoclonal antibody inhibits antihemorrhagic activity in Virginia opossum serum when mixed in equal amounts. The inhibition of antihemorrhagins by DV-2LD#2 monoclonal antibody suggests specificity. DV-2LD#2 monoclonal antibody does not recognize antihemorrhagins in gray woodrat (Neotoma micropus) serum. The five-step western blot reveals two well-defined bands which represent hemorrhagins found in Western diamondback rattlesnake (Crotalus atrox) venom. Venoms from 15 different snake species were examined to determine the usefulness of the five-step western blot. Other hemorrhagic venoms (Great Basin rattlesnake (C. viridis lutosus), Prairie rattlesnake (C. viridis viridis), Tancitaran dusky rattlesnake (C. pusillus), Northern Mojave rattlesnake (C. scutulatus scutulatus type B) and Northern Pacific rattlesnake (C. v. oreganus)) had one single band in the five-step western blot. DV-2LD#2 did not bind to the non-hemorrhagic venoms and reacted with 50% of the hemorrhagic venoms used in this study. The monoclonal antibody, CAH

Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.

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James Weger-Lucarelli

Full Text Available Chikungunya virus (CHIKV and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses.Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B. Vaccination studies in mice (both live and inactivated virus revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized.Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies.

Serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide

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Jinjiang He

2015-04-01

Full Text Available Objectives: The aim of this study has been to investigate serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide (DMF. Material and Methods: Seventy-two workers and 72 healthy controls participated in the study. All subjects underwent complete physical examinations and abdominal ultrasound examination. Serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and c-glutamyl transpeptidase (c-GT were determined by an auto-chemistry analyzer. The data of airborne concentrations of DMF was obtained from the local Center of Disease Control and Prevention. The level of urine N-acetyl-S-(N-methylcarbamoylcysteine (AMCC was measured by means of high-performance liquid chromatography. Results: Time weighted average (TWA concentration of the DMF in workplace was 18.6 (range: 9.8–36.2 mg/m3. The concentration of the AMCC in workers’ urine was 28.32 (range: 1.8–58.6 mg/l and 9 workers’ AMCC exceeded the biological exposure index (40 mg/l. Thirty-one workers reported gastrointestinal symptoms (abdominal pain, nausea, anorexia and 10 workers reported headache, dizziness and/or palpitation in the exposed group. Serum analysis revealed that both the mean of serum activities of liver enzymes (ALT, AST and c-GT and the percentage of workers with abnormal liver function were significantly higher in the exposed group as compared to the controls. Conclusions: Dimethylformamide can cause liver damage even if air concentration is in the sub-threshold limit value (sub-TLV level. The protection of skin contact against the exposure to the DMF might be a critical issue as far as the occupational health is concerned.

The effects of Zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones

International Nuclear Information System (INIS)

Sadighi, A.; Moradi, A.; Roshan, Marjan M.; Ostadrahimi, A.

2009-01-01

Objective was to determine the effect of zinc supplementation on callus information, serum zinc and alkaline phosphatase activity in humans. This randomized, double-blind, placebo controlled clinical trial was conducted on 60 patients with traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August to December 2007. Subjects were randomly divided into 2 groups: cases (n=30), receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the controls (n=30), receiving placebo for 60 days. Individual and clinical information was determined by a questionnaire: nutritional intake by 3 days food records at the beginning and the end of trial. Serum zinc and alkaline phosphatase was measured by atomic absorption spectroscopy and by enzymatic method. Callus information during fracture healing was evaluated by radiography of the bone. There was no significant difference in physical activity, gender, age, type of fractures and nutrient intake, between the 2 groups. The administration of zinc caused a significant elevation of serum zinc and alkaline phosphatase activity. Assessment of bone x-rays showed a significant progress in callus formation in cases compared to the controls. This study shows that zinc supplementation can stimulate fracture healing, however, it needs further study. (author)

Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

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Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

2014-01-01

Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (pLyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.

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Trentini, Alessandro; Manfrinato, Maria C; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A; Baldi, Eleonora; Tola, Maria R; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico

2015-08-01

The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity. © The Author(s), 2015.

Climate Neutral Campus Key Terms and Definitions | Climate Neutral Research

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Campuses | NREL Neutral Campus Key Terms and Definitions Climate Neutral Campus Key Terms and Definitions The term climate neutral evolved along with net zero and a number of other "green" and accuracy in these areas lets research campuses know exactly how close they are to climate

Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions.

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Joshua W Wang

Full Text Available Antibodies specific for neutralizing epitopes in either Human papillomavirus (HPV capsid protein L1 or L2 can mediate protection from viral challenge and thus their accurate and sensitive measurement at high throughput is likely informative for monitoring response to prophylactic vaccination. Here we compare measurement of L1 and L2-specific neutralizing antibodies in human sera using the standard Pseudovirion-Based Neutralization Assay (L1-PBNA with the newer Furin-Cleaved Pseudovirion-Based Neutralization Assay (FC-PBNA, a modification of the L1-PBNA intended to improve sensitivity towards L2-specific neutralizing antibodies without compromising assay of L1-specific responses. For detection of L1-specific neutralizing antibodies in human sera, the FC- PBNA and L1-PBNA assays showed similar sensitivity and a high level of correlation using WHO standard sera (n = 2, and sera from patients vaccinated with Gardasil (n = 30 or an experimental human papillomavirus type 16 (HPV16 L1 VLP vaccine (n = 70. The detection of L1-specific cross-neutralizing antibodies in these sera using pseudovirions of types phylogenetically-related to those targeted by the L1 virus-like particle (VLP vaccines was also consistent between the two assays. However, for sera from patients (n = 17 vaccinated with an L2-based immunogen (TA-CIN, the FC-PBNA was more sensitive than the L1-PBNA in detecting L2-specific neutralizing antibodies. Further, the neutralizing antibody titers measured with the FC-PBNA correlated with those determined with the L2-PBNA, another modification of the L1-PBNA that spacio-temporally separates primary and secondary receptor engagement, as well as the protective titers measured using passive transfer studies in the murine genital-challenge model. In sum, the FC-PBNA provided sensitive measurement for both L1 VLP and L2-specific neutralizing antibody in human sera. Vaccination with TA-CIN elicits weak cross-protective antibody in a

Similar effectiveness of Fab and F(ab')2 antivenoms in the neutralization of hemorrhagic activity of Vipera berus snake venom in mice

OpenAIRE

Lomonte, Bruno; León Montero, Guillermo; Hanson, Lars Ake

1996-01-01

The ability of two antivenoms to Vipera spp., consisting of Fab (Therapeutic Antibodies), or of F(ab′)2 (Zagreb Institute of Immunology) antibody fragments, to neutralize the hemorrhagic activity of Vipera berus snake venom in mice, was compared. First, the neutralizing potency was determined by in vitro preincubation of venom and antivenom, followed by intradermal injection into mice and subsequent measurement of the hemorrhagic area. Both antivenoms had the same anti-hemorrhagic potency, in...

Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

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Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

1996-06-01

A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

Study of iodine-iodate isotopic exchange reaction in neutral aqueous solutions by radiotracer technique

International Nuclear Information System (INIS)

Tripathi, R.; Ram, K.D.

1993-01-01

The isotopic exchange of iodine atoms in neutral aqueous solutions of iodate ions and iodine (in KI) is found to obey the rate law R = k [IO 3 - ] 0.4 [I 2 ] 1.2 at 175 o C. The addition of neutral ionic salts, e.g. KCl and KNO 3 , in the reaction mixture showed a slight catalytic effect on the exchange rate. Further, the kinetic salt effect indicated the involvement of at least one neutral species on the rate-determining step. The activation energy in neutral aqueous solutions of iodate ions and iodine is found to be 86 ± 3 kJ mol -1 , which decreases in the presence of KCl (79 ± 3 kJ mol -1 and KNO 3 (82 + 3 kJ mol -1 ). The activation parameters, viz. free energy of activation, enthalpy of activation and entropy of activation, were also calculated. Based on these results, an association-dissociation type of reaction mechanism is proposed for this exchange reaction in neutral aqueous medium, similar to that proposed earlier for iodide-iodate isotopic exchange reaction in neutral aqueous solutions, nitrate eutectic melts and iodide-iodate melts. (author)

Evaluation of Serum Lactate Dehydrogenase Activity in a Virtual Environment

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V.M.T. Trindade

2013-05-01

Full Text Available Introduction: Lactate dehydrogenase is a citosolic enzyme involved in reversible transformation of pyruvate to lactate. It participates in anaerobic glycolysis of skeletal muscle and red blood cells, in liver gluconeogenesis and in aerobic metabolism of heart muscle. The determination of its activity helps in the diagnosis of various diseases, because it is increased in serum of patients suffering from myocardial infarction, acute hepatitis, muscular dystrophy and cancer. This paper presents a learning object, mediated by computer, which contains the simulation of the laboratory determination serum lactate dehydrogenase activity measured by the spectrophotometric method, based in the decrease of absorbance at 340 nm. Materials and Methods: Initially, pictures and videos were obtained recording the procedure of the methodology. The most representative images were selected, edited and inserted into an animation developed with the aid of the tool Adobe ® Flash ® CS3. The validation of the object was performed by the students of Biochemistry I (Pharmacy-UFRGS from the second semester of 2009 and both of 2010. Results and Discussion: The analysis of students' answers revealed that 80% attributed the excellence of the navigation program, the display format and to aid in learning. Conclusion: Therefore, this software can be considered an adequate teaching resource as well as an innovative support in the construction of theoretical and practical knowledge of Biochemistry. Available at: http://www6.ufrgs.br/gcoeb/LDH

Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

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Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

2017-09-01

There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

The investigation of anti-inflammatory activity of Yi Guanjian decoction by serum metabonomics approach.

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Shui, Sufang; Cai, Xiaorong; Huang, Rongqing; Xiao, Bingkun; Yang, Jianyun

2017-01-30

Yi Guanjian (YGJ), one of the Chinese herbal medicines most commonly used in western countries, reported to possess significant anti-inflammatary effects that inhibit the process of inflammation. However, the mechanisms underlying its anti-inflammation effects remain largely unresolved. This study was aimed to investigate the anti-inflammatory activity of YGJ and to explore its potential anti-inflammatory mechanisms by serum metabonomics approach. An xylene-induced mouse right-ear-edema model was used as an inflammatory response in vivo model. Ear edema, prostaglandin E2 (PGE 2 ) and Tumor-Necrosis-Factor-alpha (TNF-α) were detected. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after YGJ administration and further integration of metabolic networks. The results showed that YGJ alleviated ear edema and decreased serum PGE 2 and TNF-α levels. Fourteen biomarkers were screened, and the levels were all reversed to different degrees after YGJ administration. These biomarkers were mainly related to linoleic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism and citrate cycle (TCA cycle). In metabolic networks, glycine and pyruvate were node molecules. This indicated that YGJ could significantly inhibit inflammatory response triggered by acute local stimulation and exerted anti-inflammatory activity mainly by regulating node molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are protective in a mouse passive transfer model.

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M Keith Howard

Full Text Available BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. METHODS: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species. CONCLUSIONS: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

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Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K

2017-08-01

The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

Neutrality Versus Materiality: A Thermodynamic Theory of Neutral Surfaces

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Rémi Tailleux

2016-09-01

Full Text Available In this paper, a theory for constructing quasi-neutral density variables γ directly in thermodynamic space is formulated, which is based on minimising the absolute value of a purely thermodynamic quantity J n . Physically, J n has a dual dynamic/thermodynamic interpretation as the quantity controlling the energy cost of adiabatic and isohaline parcel exchanges on material surfaces, as well as the dependence of in-situ density on spiciness, in a description of water masses based on γ, spiciness and pressure. Mathematically, minimising | J n | in thermodynamic space is showed to be equivalent to maximising neutrality in physical space. The physics of epineutral dispersion is also reviewed and discussed. It is argued, in particular, that epineutral dispersion is best understood as the aggregate effect of many individual non-neutral stirring events (being understood here as adiabatic and isohaline events with non-zero buoyancy, so that it is only the net displacement aggregated over many events that is approximately neutral. This new view resolves an apparent paradox between the focus in neutral density theory on zero-buoyancy motions and the overwhelming evidence that lateral dispersion in the ocean is primarily caused by non-zero buoyancy processes such as tides, residual currents and sheared internal waves. The efficiency by which a physical process contributes to lateral dispersion can be characterised by its energy signature, with those processes releasing available potential energy (negative energy cost being more efficient than purely neutral processes with zero energy cost. The latter mechanism occurs in the wedge of instability, and its source of energy is the coupling between baroclinicity, thermobaricity, and density compensated temperature/salinity anomalies. Such a mechanism, which can only exist in a salty ocean, is speculated to be important for dissipating spiciness anomalies and neutral helicity. The paper also discusses potential

Serum hepatic biochemistry and electrophoretic protein profile of healthy and Ehrlich tumor-bearing mice treated with extracts of Agaricus blazei Murill

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Durval Verçosa Junior

2016-04-01

Full Text Available Compounds isolated from Agaricus blazei Murill represent a group of promising natural immunomodulators for use in the treatment of neoplasms. We have evaluated the serum biochemical profile of healthy and Ehrlich tumor-bearing mice treated with different extracts of A. blazei. Total, supernatant, and polysaccharide extracts of A. blazei were obtained from suspensions (at acidic or neutral pH kept in a water bath at 60 °C or in an ultrasonic bath at 37 °C. After oral administering the extracts to mice for 21 days, blood samples were collected for determination of aspartate aminotransferase (AST, alanine aminotransferase (ALT, creatine kinase (CK, urea, total protein, albumin, globulins, and alpha-, beta- and gamma-globulin fractions. The presence of the tumor led to a significant increase in serum CK and AST activities and in the concentrations of total globulin and the gamma-globulin fraction, and to a decrease in the albumin and alpha2-globulin levels. The polysaccharide extracts of A. blazei reduced the serum AST and ALT activities, probably due to a hepatoprotective effect. In addition, polysaccharide and supernatant extracts inhibited the tumor-induced increase in gamma-globulin levels. Thus, the supernatant and polysaccharide fractions of the extract of A. blazei have potential for use in complementary antineoplastic treatments.

Chemical conditions of the Japanese neutral geothermal reservoirs

International Nuclear Information System (INIS)

Chiba, H.

1991-01-01

The aqueous speciation were calculated for fluids of seven Japanese geothermal systems. The aqueous composition as well as CO 2 partial pressure of fluid in neutral pH geothermal reservoir are controlled by silicate, calcite and anhydrite minerals. The chemical composition of neutral pH geothermal reservoir can be predictable if two parameters (e.g. temperature and one of the cation activities) are provided. (author)

Multiplex profiling of tumor-associated proteolytic activity in serum of colorectal cancer patients.

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Yepes, Diego; Costina, Victor; Pilz, Lothar R; Hofheinz, Ralf; Neumaier, Michael; Findeisen, Peter

2014-06-01

The monitoring of tumor-associated protease activity in blood specimens has recently been proposed as new diagnostic tool in cancer research. In this paper, we describe the screening of a peptide library for identification of reporter peptides (RPs) that are selectively cleaved in serum specimens from colorectal cancer patients and investigate the benefits of RP multiplexing. A library of 144 RPs was constructed that contained amino acid sequences of abundant plasma proteins. Proteolytic cleavage of RPs was monitored with MS. Five RPs that were selectively cleaved in serum specimens from tumor patients were selected for further validation in serum specimens of colorectal tumor patients (n = 30) and nonmalignant controls (n = 60). RP spiking and subsequent quantification of proteolytic fragments with LC-MS showed good reproducibility with CVs always below 26%. The linear discriminant analysis and PCA revealed that a combination of RPs for diagnostic classification is superior to single markers. Classification accuracy reached 88% (79/90) when all five markers were combined. Functional protease profiling with RPs might improve the laboratory-based diagnosis, monitoring and prognosis of malignant disease, and has to be evaluated thoroughly in future studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors

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Xiaoli Zhang

Full Text Available OBJECTIVE: One approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs. It is suspected that SP plasma has strongly neutralizing antibodies (NAb targeting specific HIV viral epitopes. METHODS: NAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from hightiter NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes. RESULTS: SPs had significantly more plasma neutralizing activity than typical progressors (TPs (p = 0.04. P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction. CONCLUSION: Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.

STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .

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Seham Ragab

2015-02-01

Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

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Rich, Tyvin; Innominato, Pasquale F; Boerner, Julie; Mormont, M Christine; Iacobelli, Stefano; Baron, Benoit; Jasmin, Claude; Lévi, Francis

2005-03-01

Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

DEFF Research Database (Denmark)

Draborg, Anette H; Lydolph, Magnus; Westergaard, Marie

2015-01-01

, FLCs' association with Epstein-Barr virus (EBV) antibodies was examined. METHODS: Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations......OBJECTIVE: In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore...... of serum FLCs due to decreased clearance. RESULTS: Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (pdisease activity (SLE disease activity...

Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

International Nuclear Information System (INIS)

Basken, Nathan E.; Mathias, Carla J.; Lipka, Alexander E.; Green, Mark A.

2008-01-01

Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: 64 Cu-labeled diacetyl bis(N 4 -methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N 4 -methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0±0.1%, 5.3±0.2% and 38.6±0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations.

Science.gov (United States)

Matinlauri, Irma H; Kyllönen, Lauri E J; Salmela, Kaija T; Helin, Heikki; Pelzl, Steffen; Süsal, Caner

2005-12-27

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (PsCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

Serum inflammatory mediators as markers of human Lyme disease activity.

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Mark J Soloski

Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection.

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Gene S Tan

2016-04-01

Full Text Available In the early spring of 2013, Chinese health authorities reported several cases of H7N9 influenza virus infections in humans. Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually. In order to characterize the antibody response to the H7N9 virus we generated several mouse monoclonal antibodies against the hemagglutinin of the A/Shanghai/1/13 (H7N9 virus. Of particular note are two monoclonal antibodies, 1B2 and 1H5, that show broad reactivity to divergent H7 hemagglutinins. Monoclonal antibody 1B2 binds to viruses of the Eurasian and North American H7 lineages and monoclonal antibody 1H5 reacts broadly to virus isolates of the Eurasian lineage. Interestingly, 1B2 shows broad hemagglutination inhibiting and neutralizing activity, while 1H5 fails to inhibit hemagglutination and demonstrates no neutralizing activity in vitro. However, both monoclonal antibodies were highly protective in an in vivo passive transfer challenge model in mice, even at low doses. Experiments using mutant antibodies that lack the ability for Fc/Fc-receptor and Fc/complement interactions suggest that the protection provided by mAb 1H5 is, at least in part, mediated by the Fc-fragment of the mAb. These findings highlight that a protective response to a pathogen may not only be due to neutralizing antibodies, but can also be the result of highly efficacious non-neutralizing antibodies not readily detected by classical in vitro neutralization or hemagglutination inhibition assays. This is of interest because H7 influenza virus vaccines induce only low hemagglutination inhibiting antibody titers while eliciting robust antibody titers as measured by ELISA. Our data suggest that these binding but non-neutralizing antibodies contribute to protection in vivo.

Non-Neutralizing Antibodies Directed against HIV and Their Functions

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Luzia M. Mayr

2017-11-01

Full Text Available B cells produce a plethora of anti-HIV antibodies (Abs but only few of them exhibit neutralizing activity. This was long considered a profound limitation for the enforcement of humoral immune responses against HIV-1 infection, especially since these neutralizing Abs (nAbs are extremely difficult to induce. However, increasing evidence shows that additional non-neutralizing Abs play a significant role in decreasing the viral load, leading to partial and sometimes even total protection. Mechanisms suspected to participate in protection are numerous. They involve the Fc domain of Abs as well as their Fab part, and consequently the induced Ab isotype will be determinant for their functions, as well as the quantity and quality of the Fc-receptors (FcRs expressed on immune cells. Fc-mediated inhibitory functions, such as Ab-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, aggregation, and even immune activation have been proposed. However, as for nAbs, the non-neutralizing activities are limited to a subset of anti-HIV Abs. An improved in-depth characterization of the Abs displaying these functional responses is required for the development of new vaccination strategies, which aim to selectively trigger the B cells able to induce the right functional Ab combinations both at the right place and at the right time. This review summarizes our current knowledge on non-neutralizing functional inhibitory Abs and discusses the potential benefit of inducing them via vaccination. We also provide new insight into the roles of the FcγR-mediated Ab therapeutics in clinical trials for HIV diseases.

Modeling of the lithium based neutralizer for ITER neutral beam injector

Energy Technology Data Exchange (ETDEWEB)

Dure, F., E-mail: franck.dure@u-psud.fr [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France); Lifschitz, A.; Bretagne, J.; Maynard, G. [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France); Simonin, A. [IRFM, Institut de Recherche sur la Fusion Magnetique, CEA Cadarache, 13108 Saint-Paul lez Durance (France); Minea, T. [LPGP, Laboratoire de Physique des Gaz et Plasmas, CNRS-Universite Paris Sud, Orsay (France)

2012-04-04

Highlights: Black-Right-Pointing-Pointer We compare different lithium based neutraliser configurations to the deuterium one. Black-Right-Pointing-Pointer We study characteristics of the secondary plasma and the propagation of the 1 MeV beam. Black-Right-Pointing-Pointer Using lithium increases the neutralisation effiency keeping correct beam focusing. Black-Right-Pointing-Pointer Using lithium also reduces the backstreaming effect in direction of the ion source. - Abstract: To achieve thermonuclear temperatures necessary to produce fusion reactions in the ITER Tokamak, additional heating systems are required. One of the main method to heat the plasma ions in ITER will be the injection of energetic neutrals (NBI). In the neutral beam injector, negative ions (D{sup -}) are electrostatically accelerated to 1 MeV, and then stripped of their extra electron via collisions with a target gas, in a structure known as neutralizer. In the current ITER specification, the target gas is deuterium. It has been recently proposed to use lithium vapor instead of deuterium as target gas in the neutralizer. This would allow to reduce the gas load in the NBI vessel and to improve the neutralization efficiency. A Particle-in-Cell Monte Carlo code has been developed to study the transport of the beams and the plasma formation in the neutralizer. A comparison between Li and D{sub 2} based neutralizers made with this code is presented here, as well as a parametric study on the geometry of the Li based neutralizer. Results demonstrate the feasibility of a Li based neutralizer, and its advantages with respect to the deuterium based one.

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

Science.gov (United States)

Peng, You-Fan; Deng, Yi-Bin

2017-06-01

- Bilirubin has strong anti-inflammatory and antioxidative stress action. Progression of inflammation involving arteries is a crucial activator in pathogenesis of Takayasu arteritis (TA). - To investigate the relationship between serum bilirubin and TA. - Our study involved 115 consecutive TA patients. Patients with active-phase disease were followed and received prednisone therapy. - Lower concentrations of serum bilirubin were detected in TA patients compared with healthy subjects (0.6 ± 0.31 versus 0.7 ± 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA patients were lower than those in inactive patients (0.5 ± 0.20 versus 0.8 ± 0.32 mg/dL, P bilirubin correlated positively with total protein (r = 0.193, P = .04) and negatively with C-reactive protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532, P bilirubin was associated with a 1.10 times increase in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856-0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation rate (β = -0.170, P bilirubin in predicting active TA patients was 0.802. Serum bilirubin levels were found to be significantly increased after prednisone treatment (0.5 ± 0.20 versus 0.7 ± 0.15 mg/dL, P = .002). - Lower serum bilirubin levels are associated with TA, and serum bilirubin may be influenced by prednisone therapy in active TA patients. Serum bilirubin levels in TA patients correlate negatively with erythrocyte sedimentation rate.

Comparison of Deferoxamine, Activated Charcoal, and Vitamin C in Changing the Serum Level of Fe in Iron Overloaded Rats

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Reza Ghafari

2014-02-01

Full Text Available Background: Iron is an essential mineral for normal cellular physiology but its overload can lead to cell injury. For many years, deferoxamine injection has been used as an iron chelator for treatment of iron overload. The aim of this study is to compare oral deferoxamine, activated charcoal, and vitamin C, as an absorbent factor of Fe, in changing the serum level of iron in iron overload rats. Methods: In this experimental study, all groups were administered 150 mg iron dextran orally by gavage. After eight hours, rats in the first group received oral deferoxamine while those in the second and third groups received oral activated charcoal 1 mg/kg and oral vitamin C 150 mg, respectively. Then, serum levels of iron ware measured in all rats. Results: The mean serum level of iron in rats that received oral deferoxamine was 258.11±10.49 µg/dl, whereas mean levels of iron in charcoal and vitamin C groups were 380.88±11.21 µg/dl and 401.22±13.28 µg/dl, respectively. None of the measurements were within safety limits of serum iron. Conclusion: It seems that oral deferoxamine per se may not help physicians in the management of cases presented with iron toxicity. Activated charcoal did not reduce serum iron significantly in this study and further investigations may be warranted to assess the potential clinical utility of its mixture with oral deferoxamine as an adjunct in the clinical management of iron ingestions.

Testosterone like Activity of Ethanolic and Aqueous Extracts of Mucuna pruriens Seeds and its Effects on Serum Biochemical Metabolites in Immature Male Rats

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Nazir Ahmad*, Zia-ur-Rahman1, Nafees Akhtar and Shujait Ali

2012-01-01

Full Text Available Testosterone like activity of seeds of Mucuna pruriens and its effects on serum biochemical metabolites in immature male rats were investigated. Forty eight immature male rats were divided into four equal groups. Rats of groups A and B were orally given ethanolic and aqueous extracts of Mucuna pruriens seeds daily at the dose rate of 500 mg/kg body weight, respectively, for 14 days. Rats of group C were injected with testosterone at the dose rate of 2.5 mg/kg body weight daily, while rats of group D served as controls. After 7 days, six rats from each group were euthanized, while the remaining six rats from each group were euthanized after 14 days of treatment. Rats given ethanolic extract gained higher weight compared to controls (P<0.05. Testis weight was the highest in rats treated with testosterone. The effect of treatments on the weight of the liver and the kidneys was non significant. Rats given ethanolic or aqueous extract had higher serum testosterone concentration than controls. Similarly, rats given ethanolic or aqueous extract had higher serum total proteins, total cholesterol and HDL cholesterol compared to controls. Moreover, ethanolic extract treated rats also had higher total cholesterol and HDL cholesterol than aqueous extract treated rats. However, differences in serum total proteins, total cholesterol and HDL cholesterol between control and testosterone injected rats were non significant. Serum triglycerides, LDL cholesterol and ALT activity did not differ among rats of four groups. Serum AST activity and urea were lower in rats treated with ethanolic or aqueous extract compared to controls. Thus, seeds of Mucuna pruriens had testosterone like activity and increased serum total proteins, total cholesterol and HDL cholesterol, with no adverse effects on the serum LDL cholesterol, liver or kidney functions.

Serum analysis of coronary heart disease patients by instrumental neutron activation analysis

International Nuclear Information System (INIS)

Jong-Hwa Moon; Yong-Sam Chung; Kwang-Won Park; Okhee Lee

2007-01-01

Due to changes of the dietary pattern and life style, cardiovascular diseases like coronary heart disease (CHD) have been increasing in Korea. In this study, the levels of the serum minerals such as Na, Cl, K, Ca, Fe, Zn and Se for 75 patients with CHD and 25 normal persons, who were older than the age of 40, were investigated by instrumental neutron activation analysis. For analytical quality control, the reference materials, INSPQ and Seronorm, were analyzed simultaneously. The relative errors of the analytical values for the reference materials were within 10% of the certified values. The average concentrations of Na, Cl, K, Ca, Fe, Zn and Se in the serum of the male patients were 2,850±260 mg/l, 3,400±310 mg/l, 160±30 mg/l, 80.9±11.7 mg/l, 1.57±0.73 mg/l, 0.094±0.019 mg/l and 0.795±0.163 mg/l, respectively. The concentrations of Na, Cl, K, Ca, Fe, Zn and Se in the serum of the female patients were 2,890±240 mg/l, 3,430±350 mg/l, 169±27 mg/l, 81.8±13.0 mg/l, 1.26±0.44 mg/l, 0.099±0.015 mg/l and 0.769±0.105 mg/l, respectively. In a comparison between the patients and the normal group for both genders, while the levels of the elemental concentrations such as Na, Cl, K, Ca, Fe and Se were similar, the Zn concentration level of the CHD patients was significantly lower than that of the normal ones. The present study showed that the Zn concentration in the serum could be associated with CHD in Korean adults. (author)

IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.

Science.gov (United States)

Schlaudecker, Elizabeth P; Steinhoff, Mark C; Omer, Saad B; McNeal, Monica M; Roy, Eliza; Arifeen, Shams E; Dodd, Caitlin N; Raqib, Rubhana; Breiman, Robert F; Zaman, K

2013-01-01

Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the

Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

DEFF Research Database (Denmark)

Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

2007-01-01

BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

Reporter gene assay for the quantification of the activity and neutralizing antibody response to TNFα antagonists

DEFF Research Database (Denmark)

Lallemand, Christophe; Kavrochorianou, Nadia; Steenholdt, Casper

2011-01-01

A cell-based assay has been developed for the quantification of the activity of TNFα antagonists based on human erythroleukemic K562 cells transfected with a NFκB regulated firefly luciferase reporter-gene construct. Both drug activity and anti-drug neutralizing antibodies can be quantified...... with a high degree of precision within 2h, and without interference from cytokines and other factors known to activate NFκB. The assay cells also contain the Renilla luciferase reporter gene under the control of a constitutive promoter that allows TNFα-induced firefly luciferase activity to be normalized...... relative to Renilla luciferase expression. Thus, results are independent of cell number or differences in cell viability, resulting in intra and inter assay coefficients of variation of 10% or less. Normalization of results relative to the expression of an internal standard also provides a means...

Modeling of modification experiments involving neutral-gas release

International Nuclear Information System (INIS)

Bernhardt, P.A.

1983-01-01

Many experiments involve the injection of neutral gases into the upper atmosphere. Examples are critical velocity experiments, MHD wave generation, ionospheric hole production, plasma striation formation, and ion tracing. Many of these experiments are discussed in other sessions of the Active Experiments Conference. This paper limits its discussion to: (1) the modeling of the neutral gas dynamics after injection, (2) subsequent formation of ionosphere holes, and (3) use of such holes as experimental tools

Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

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Sébastien Lenglet

2014-01-01

Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

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Atamer, Y. [Department of Medical Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Atamer, A. [Ministry of Health Haydarpaşa Numune Training and Research Hospital, Division of Gastroenterology, Department of Internal Medicine, Istanbul, Turkey, Division of Gastroenterology, Department of Internal Medicine, Ministry of Health Haydarpaşa Numune Training and Research Hospital, Istanbul (Turkey); Can, A.S. [Termal Professional School, Yalova University, Yalova (Turkey); Hekimoğlu, A. [Dicle University, Department of Pharmacology, Faculty of Medicine, Diyarbakir, Turkey, Department of Pharmacology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Ilhan, N. [Firat University, Department of Medical Biochemistry, Faculty of Medicine, Elaziğ, Turkey, Department of Medical Biochemistry, Faculty of Medicine, Fırat University, Elazığ (Turkey); Yenice, N. [Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Harran University, Urfa (Turkey); Koçyiğit, Y. [Dicle University, Department of Physiology, Faculty of Medicine, Diyarbakir, Turkey, Department of Physiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey)

2013-06-25

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m{sup 2}], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Atamer, Y.; Atamer, A.; Can, A.S.; Hekimoğlu, A.; Ilhan, N.; Yenice, N.; Koçyiğit, Y.

2013-01-01

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m 2 ], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality

Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity

International Nuclear Information System (INIS)

Kawaguchi, K.; Sone, T.; Tsuboi, H.; Sassa, H.; Okumura, K.; Hashimoto, H.; Ito, T.; Satake, T.

1991-01-01

To test the hypothesis that simultaneous dual energy single photon emission computed tomography (SPECT) with technetium-99m (99mTc) pyrophosphate and thallium-201 (201TI) can provide an accurate estimate of the size of myocardial infarction and to assess the correlation between infarct size and peak serum creatine kinase activity, 165 patients with acute myocardial infarction underwent SPECT 3.2 +/- 1.3 (SD) days after the onset of acute myocardial infarction. In the present study, the difference in the intensity of 99mTc-pyrophosphate accumulation was assumed to be attributable to difference in the volume of infarcted myocardium, and the infarct volume was corrected by the ratio of the myocardial activity to the osseous activity to quantify the intensity of 99mTc-pyrophosphate accumulation. The correlation of measured infarct volume with peak serum creatine kinase activity was significant (r = 0.60, p less than 0.01). There was also a significant linear correlation between the corrected infarct volume and peak serum creatine kinase activity (r = 0.71, p less than 0.01). Subgroup analysis showed a high correlation between corrected volume and peak creatine kinase activity in patients with anterior infarctions (r = 0.75, p less than 0.01) but a poor correlation in patients with inferior or posterior infarctions (r = 0.50, p less than 0.01). In both the early reperfusion and the no reperfusion groups, a good correlation was found between corrected infarct volume and peak serum creatine kinase activity (r = 0.76 and r = 0.76, respectively; p less than 0.01)

The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies

DEFF Research Database (Denmark)

Arendrup, M; Akerblom, L; Heegaard, P M

1995-01-01

The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates...... patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3...... to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding...

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

International Nuclear Information System (INIS)

Shedlock, Devon J.; Bailey, Michael A.; Popernack, Paul M.; Cunningham, James M.; Burton, Dennis R.; Sullivan, Nancy J.

2010-01-01

Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.

Species dependence of [{sup 64}Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

Energy Technology Data Exchange (ETDEWEB)

Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: nbasken@purdue.edu; Mathias, Carla J. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Lipka, Alexander E. [Department of Statistics, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

2008-04-15

Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: {sup 64}Cu-labeled diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0{+-}0.1%, 5.3{+-}0.2% and 38.6{+-}0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

Science.gov (United States)

Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Multiple free-radical scavenging (MULTIS) capacity in cattle serum.

Science.gov (United States)

Sueishi, Yoshimi; Kamogawa, Erisa; Kimura, Anna; Kitahara, Go; Satoh, Hiroyuki; Asanuma, Taketoshi; Oowada, Shigeru

2017-01-01

Multiple free-radical scavenging (MULTIS) activity in cattle and human sera was evaluated with electron spin resonance spectroscopy. Scavenging rates against six active species, namely hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen were quantified. The difference in the electron spin resonance signal intensity in the presence and absence of the serum was converted into the scavenging rates. Comparative MULTIS measurements were made in sera from eight beef cattle, three fetal calves and fifteen healthy human volunteers. Further, we determined the MULTIS value of albumin, the most abundant component in serum. MULTIS values in cattle sera indicated higher scavenging activity against most free radical species tested than human sera. In particular, cattle serum scavenging activities against superoxide and methyl radical were higher than human serum by 2.6 and 3.7 fold, respectively. In cattle serum, albumin appears to play a dominant role in MULTIS activity, but in human serum that is not the case. Previous data indicated that the abundance of uric acid in bovine blood is nearly 80% less than humans; however, this difference does not explain the deviation in MULTIS profile.

Quantum Chemical Investigation on the Antioxidant Activity of Neutral and Anionic Forms of Juglone: Metal Chelation and Its Effect on Radical Scavenging Activity

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Aymard Didier Fouegue Tamafo

2017-01-01

Full Text Available The chelation ability of divalent Mg, Ca, Fe, Co, Ni, Cu, Zn, and monovalent Cu ions by neutral and anionic forms of juglone has been investigated at DFT/B3LYP/6-31+G(d,p level of theory in gas and aqueous phases. It is noteworthy that only the 1 : 1 stoichiometry was considered herein. The effects of these metals on the radical scavenging activity of neutral juglone were evaluated via the usual descriptors of hydrogen atom transfer. According to our results, metal chelation by the two forms of juglone was spontaneous and exothermic in both media. Based on the binding energies, Cu(II ion showed the highest affinity for the ligands. QTAIM analyses identified the metal-ligand bonds as intermediate type interactions in all the chelates, except those of Ca and Mg. It was also found that the chelates were better radical scavengers than the ligands. In the gas phase, the scavenging activity of the compounds was found to be governed by direct hydrogen atom transfer, the Co(II chelate being the most reactive. In the aqueous phase also, the sequential proton loss electron transfer was preferred by all the molecules, while the Cu(II chelates were the most reactive.

Study of neutral particles

International Nuclear Information System (INIS)

Bartel, W.; Bulos, F.; Eisner, A.

1975-01-01

The range of physics problems for which a detector emphasizing neutrals is most suitable is discussed. The primary goals are the all neutrals cross section, sigma/sub o/ (e + e - → neutrals), the characterization of the neutral energy in multi-hadronic events, the search for monoenergetic photons, and good sensitivity in the difficult region of low energy photons. Those features of multi-hadronic events which are most relevant to a neutral detector were calculated using a jet model with parameters extrapolated from SPEAR energies. These distributions are presented and discussed

Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

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Deepak K Kaushik

Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147 is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

Science.gov (United States)

Kaushik, Deepak K; Yong, Heather Y F; Hahn, Jennifer N; Silva, Claudia; Casha, Steven; Hurlbert, R John; Jacques, Francois H; Lisak, Robert; Khan, Omar; Ionete, Carolina; Larochelle, Catherine; Prat, Alex; Bar-Or, Amit; Yong, V Wee

2016-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

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Gianfranco Cervellin

Full Text Available OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years. Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001 was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning.

Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

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Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Moltó, Javier; Poy, Rosario; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

2016-04-01

There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

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Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

2012-09-28

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

Science.gov (United States)

Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

2012-01-01

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

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Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

2016-05-01

CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

Platelet activating factor-acylhydrolase (PAF-ase) activity is higher in serum of men than women and is related to levels of low density lipoprotein (LDL)

International Nuclear Information System (INIS)

Farr, R.S.; Howell, S.E.; Wardlow, M.L.

1986-01-01

PAF-ase is a specific serum enzyme that inactivates PAF by hydrolyzing acetate from the sn-2 position of the glycerol backbone. A reproducible PAF-ase activity assay was developed. A unit is based on the amount of serum required to release 3.61 +/- 0.042 pm 3 H-acetate from 10 pm 3 H-labeled PAF after incubation for 1 hr at 37 0 C. Assays on two single reference serums repeated 7 days were 0.63 +/- 0.013 U and 1.33 +/- 0.031 U. Serum from 20 normal men and 20 normal premenopausal women had significantly different (p = <0.001) levels of 1.32 +/- 0.072 U and 0.97 +/- 0.051 U respectively. They previously reported that PAF-ase is associated with B-lipoprotein. Therefore, total cholesterol (TC), LDL and high density lipoproteins (HDL) were determined on these 40 serums. Regression analysis revealed PAF-ase units were correlated with LDL (r = 0.740; p = < 0.001) and, parenthetically, with the TC (r = 0.620; p = < 0.001) but not with HDL. These correlations were similar for men and women. Thus, serum PAF-ase was partially controlled by serum LDL levels and the higher PAF-ase levels in serum from men were due in part to higher (p = < 0.01) LDL levels in men (147.6 +/- 6.9 mg/dl) as contrasted to women (119.0 +/- 7.6 mg/dl). PAF is a potent inflammatory, bronchoconstrictive and hypotensive agent. These data indicate that sex and serum LDL levels of subjects must be considered during future studies of the role of PAF vs PAF-ase in different disease states

Testosterone is inversely related to brain activity during emotional inhibition in schizophrenia.

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Ans Vercammen

Full Text Available Sex steroids affect cognitive function as well as emotion processing and regulation. They may also play a role in the pathophysiology of schizophrenia. However, the effects of sex steroids on cognition and emotion-related brain activation in schizophrenia are poorly understood. Our aim was to determine the extent to which circulating testosterone relates to brain activation in men with schizophrenia compared to healthy men during cognitive-emotional processing. We assessed brain activation in 18 men with schizophrenia and 22 age-matched healthy men during an emotional go/no-go task using fMRI and measured total serum testosterone levels on the same morning. We performed an ROI analysis to assess the relationship between serum testosterone and brain activation, focusing on cortical regions involved the emotional go/no-go task. Slower RT and reduced accuracy was observed when participants responded to neutral stimuli, while inhibiting responses to negative stimuli. Healthy men showed a robust increase in activation of the middle frontal gyrus when inhibiting responses to negative stimuli, but there was no significant association between activation and serum testosterone level in healthy men. Men with schizophrenia showed a less pronounced increase in activation when inhibiting responses to negative stimuli; however, they did show a strong inverse association between serum testosterone level and activation of the bilateral middle frontal gyrus and left insula. Additionally, increased accuracy during inhibition of response to negative words was associated with both higher serum testosterone levels and decreased activation of the middle frontal gyrus in men with schizophrenia only. We conclude that endogenous hormone levels, even within the normal range, may play an enhanced modulatory role in determining the neural and behavioural response during cognitive-emotional processing in schizophrenia.

The current state of serum biomarkers of hepatotoxicity.

Science.gov (United States)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-03-20

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

The current state of serum biomarkers of hepatotoxicity

International Nuclear Information System (INIS)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-01-01

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

The effect of Omega-3 fatty acids on serum paraoxonase activity, vitamins A, E, and C in type 2 diabetic patients

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Anis Kouchak

2011-01-01

Full Text Available Background: Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. Studies showed paraoxonase activity, and vitamin C and A levels are decreased in diabetes. The effect of omega-3 fatty acids on serum paraoxonase activity and vitamins A, E, C in patients with type 2 diabetes is not fully understood. This study aimed to determine the effect of omega-3 fatty acids on paraoxonase activity, vitamins C, A and E levels in type 2 diabetic patients. Methods: In a double-blind, placebo controlled trial, 80 type 2 diabetic patients were randomly enrolled into the study. Study subjects received daily 2714 mg of omega-3 fatty acids or placebo for 8 weeks. Ten milliliter fasting blood was collected before and after treatments. Serum paraoxonase activity and vitamin C levels were measured by spectrophotometry. Vitamin A and vitamin E were measured using high performance liquid chromatography. Nutrient intake was estimated using 24-hours dietary recall questionnaire (for 2 days before and after treatments. Dietary data were analyzed using FPII. To compare the means of variables between the two groups, independent t-test was employed. Differences between variables before and after interventions were calculated using paired t-test. Results: Serum levels of paraoxonase activity were significantly increased after omega-3 intake (126.47 IU/ml vs. 180.13 IU/ml. However, omega-3 intake caused no significant change in serum vitamin A, C, and E. Conclusions: Supplementation of omega-3 fatty acids was found to increase paraoxonase activity in diabetic patients.

A viscometric approach of pH effect on hydrodynamic properties of human serum albumin in the normal form.

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Monkos, Karol

2013-03-01

The paper presents the results of viscosity determinations on aqueous solutions of human serum albumin (HSA) at isoelectric point over a wide range of concentrations and at temperatures ranging from 5°C to 45°C. On the basis of a modified Arrhenius equation and Mooney's formula some hydrodynamic parameters were obtained. They are compared with those previously obtained for HSA in solutions at neutral pH. The activation energy and entropy of viscous flow and the intrinsic viscosity reach a maximum value, and the effective specific volume, the self-crowding factor and the Huggins coefficient a minimum value in solutions at isoelectric point. Using the dimensionless parameter [η]c, the existence of three ranges of concentrations: diluted, semi-diluted and concentrated, was shown. By applying Lefebvre's relation for the relative viscosity in the semi-dilute regime, the Mark-Houvink-Kuhn-Sakurada (MHKS) exponent was established. The analysis of the results obtained from the three ranges of concentrations showed that both conformation and stiffness of HSA molecules in solutions at isoelectric point and at neutral pH are the same.

The Effects of Physical Activity on Serum Visfatin Level: A Literature Review

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Mohsen Ghanbarzadeh

2017-06-01

Full Text Available Higher concentration of plasma visfatin in obese and diabetic subjects compared with their healthy counterparts shows visfatin relationship to obesity and overweight. This article reviewed the studies on contradictory and different notions regarding the role of physical activity in visfatin response following aerobic and resistance exercises. Recent reports on the impact of physical activity and exercise on visfatin concentration is contradictory. Some studies have identified that exercise can reduce visfatin concentration depending on the duration of physical activity and calorie expenditure, while others have not reported any changes in visfatin concentration. The present review indicated that a balanced diet, low in fat, and physical exercise (aerobic and aerobic-resistance exercises can reduce blood visfatin levels depending on the severity and duration, while resistance training alone exerts no significant effects on serum visfatin level.

Improvement of activated carbons as oxygen reduction catalysts in neutral solutions by ammonia gas treatment and their performance in microbial fuel cells

KAUST Repository

Watson, Valerie J.; Nieto Delgado, Cesar; Logan, Bruce E.

2013-01-01

Commercially available activated carbon (AC) powders from different precursor materials (peat, coconut shell, coal, and hardwood) were treated with ammonia gas at 700 C to improve their performance as oxygen reduction catalysts in neutral p

Neutral beam monitoring

International Nuclear Information System (INIS)

Fink, J.H.

1979-01-01

A neutral beam generated by passing accelerated ions through a walled cell containing a low energy neutral gas, such that charge exchange partially neutralizes the high energy beam, is monitored by detecting the current flowing through the cell wall produced by low energy ions which drift to the wall after the charge exchange. By segmenting the wall into radial and longitudinal segments various beam conditions are identified. (U.K.)

Bunched beam neutralization

International Nuclear Information System (INIS)

Gammel, G.M.; Maschke, A.W.; Mobley, R.M.

1979-01-01

One of the steps involved in producing an intense ion beam from conventional accelerators for Heavy Ion Fusion (HIF) is beam bunching. To maintain space charge neutralized transport, neutralization must occur more quickly as the beam bunches. It has been demonstrated at BNL that a 60 mA proton beam from a 750 kV Cockcroft--Walton can be neutralized within a microsecond. The special problem in HIF is that the neutralization must occur in a time scale of nanoseconds. To study neutralization on a faster time scale, a 40 mA, 450 kV proton beam was bunched at 16 MHz. A biased Faraday cup sampled the bunched beam at the position where maximum bunching was nominally expected, about 2.5 meters from the buncher. Part of the drift region, about 1.8 meters, was occupied by a series of Gabor lenses. In addition to enhancing beam transport by transverse focussing, the background cloud of electrons in the lenses provided an extra degree of neutralization. With no lens, the best bunch factor was at least 20. Bunch factor is defined here as the ratio of the distance between bunches to the FWHM bunch length. With the lens, it was hoped that the increased plasma frequency would decrease the neutralization time and cause an increase in the bunch factor. In fact, with the lens, the instantaneous current increased about three times, but the bunch factor dropped to about 10. Even with the lens, the FWHM of the bunches at the position of maximum bunching was still comparable to or less than the oscillation period of the surrounding electron plasma. Thus, the electron density in the lens must increase before neutralization could be effective in this case, or bunching should be done at a lower frequency

Serum Leptin levels do not correlate with disease activity in Rheumatoid Arthritis

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Sibel Yilmaz Oner

2015-01-01

Full Text Available Objectives Leptin, is a fat tissue hormone which effects energy expenditure , food intake , hematopoiesis, osteogenesis, angiogenesis, reproductive and immune systems. We aimed to determine serum leptin levels and investigate the association between disease activity and other parameters in RA patients. Methods Patients with RA (n=106 as the study group, healthy controls (n=52 and osteoarthritis (OA patients (n=37 as a control group were enrolled to the study. RA patients were categorized in four different groups according to DAS28 scores: remission ,low (LDA, moderate (MDA or high (HDA disease activity . Results No differences were present between the body mass indices of the three groups. Mean leptin levels in RA patients, OA group and healthy individuals were 25,60±13,41, 23,03±11,51 and 23,81±12,85 ng/ml, respectively and no significant difference was present between the groups. Nine of (8,5% RA patients were in remission, 16 (15,1% were in LDA, 40 (37,7% in MDA and 41 (38,7% were in HDA. Leptin levels did not correlate with DAS28 scores of RA patients (r=-0,12, p=0,11. Mean leptin levels in RA patients with remission was 32,65±7, 28 in LDA 23,94±10,94 in MDA 26,73±14,92 and in HDA 23,59±13,50 ng/ml (p=NS. No associations were observed between leptin levels and CRP, ESR, RF positivity and disease duration. Conclusions Our study revealed no correlation of disease activity and serum leptin levels. Therefore leptin does not seem to be an appropriate biomarker to monitorize inflammation in RA.

Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.

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Gábor Firneisz

Full Text Available BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4 and the insulin resistance index (HOMA2-IR in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD and in healthy controls (CNTRL. METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs and 82 type 2 diabetes (F/M:48/34, 62.8 yrs patients and 26 (F/M:14/12, 35.3 yrs controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes", 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests; NAFLD(NGTonly: 3.23 (p = 0.0013 vs CNTRL; NAFLD(IFG/IGT/type 2 diabetes: 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group. sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L and abnormal glucose metabolism (30.38U/L than in CNTRL (25.89U/L, p<0.001 and p = 0.013 or in T2D groups (23.97U/L, p<0.001 and p = 0.004. Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210. CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly

Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy.

Science.gov (United States)

Niebroj-Dobosz, I; Hausmanowa-Petrusewicz, I

1989-09-01

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.

Duo-Active-Neutral-Point-Clamped Multilevel Converter: An Exploration of the Fundamental Topology and Experimental Verification

DEFF Research Database (Denmark)

Dargahi, Vahid; Corzine, Keith A.; Enslin, Johan H.

2018-01-01

For medium-voltage (MV) industrial applications such as the HVDC and adjustable-speed ac-motor drives, the multilevel voltage-source converters are deemed the predominant topologies. One of the promising derived-topologies from the neutral-point-clamped (NPC) configuration is the active NPC (ANPC......) structure with an improved balanced lossdistribution performance. This paper introduces duo-ANPC (D-ANPC) converter topology, which is controlled with a new modulation technique. The suggested control method regulates the flying capacitor (FC) voltages naturally at their reference values and preserves...

Fatty acid modulated human serum albumin binding of the β-carboline alkaloids norharmane and harmane.

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Domonkos, Celesztina; Fitos, Ilona; Visy, Júlia; Zsila, Ferenc

2013-12-02

Harmane and norharmane are representative members of the large group of natural β-carboline alkaloids featured with diverse pharmacological activities. In blood, these agents are transported by human serum albumin (HSA) which has a profound impact on the pharmacokinetic and pharmacodynamic properties of many therapeutic drugs and xenobiotics. By combination of various spectroscopic methods, the present contribution is aimed to elucidate how nonesterified fatty acids (FAs), the primary endogenous ligands of HSA, affect the binding properties of harmane and norharmane. Analysis of induced circular dichroism (CD) and fluorescence spectroscopic data indicates the inclusion of the neutral form of both molecules into the binding pocket of subdomain IIIA, which hosts two FA binding sites, too. The induced CD and UV absorption spectra of harmane and norharmane exhibit peculiar changes upon addition of FAs, suggesting the formation of ternary complexes in which the lipid ligands significantly alter the binding mode of the alkaloids via cooperative allosteric mechanism. To our knowledge, it is the first instance of the demonstration of drug-FA cobinding at site IIIA. In line with these results, molecular docking calculations showed two distinct binding positions of norharmane within subdomain IIIA. The profound increase in the affinity constants of β-carbolines estimated in the presence of FAs predicts that the unbound, pharmacologically active serum fraction of these compounds strongly depends on the actual lipid binding profile of HSA.

Charge exchange measurements of MHD activity during neutral beam injection in the Princeton Large Torus and the Poloidal Divertor Experiment

International Nuclear Information System (INIS)

Goldston, R.J.; Kaita, R.; Beiersdorfer, P.; Gammel, G.; Herndon, D.L.; McCune, D.C.; Meyerhofer, D.D.

1987-01-01

The horizontally scanning, multi-angle charge exchange analysers on the Princeton Large Torus (PLT) and the Poloidal Divertor Experiment (PDX) were used to study the effects of MHD activity on the background ion distribution function and on the beam ion slowing-down process during high power neutral injection. Sawtooth oscillations were observed in the fast ion flux on PLT and PDX, and measurements with neutral beams providing local neutral density enhancement indicated that the ions were transported radially when these events occurred. With near-perpendicular injection in PDX, at the lower toroidal fields necessary to maximize the plasma beta, repetitive bursts of greatly enhanced charge exchange flux were observed. These were associated with the 'fishbone' MHD instability, and a substantial depletion of the perpendicular slowing-down spectrum below the injection energy was seen. A simple phenomenological model for this loss mechanism was developed, and its use in simulation codes has been successful in providing good agreement with the experimental data. The behaviour and characteristics of this model are well matched by direct theoretical calculations. (author)

Charge-exchange measurements of MHD activity during neutral beam injection in the Princeton Large Torus and the Poloidal Divertor Experiment

International Nuclear Information System (INIS)

Goldston, R.J.; Kaita, R.; Beiersdorfer, P.; Gammel, G.; Herndon, D.L.; McCune, D.C.; Meyerhofer, D.D.

1986-07-01

The horizontally scanning, multiangle charge-exchange analyzers on the Princeton Large Torus (PLT) and the Poloidal Divertor Experiment (PDX) were used to study the effects of MHD activity on the background ion distribution function and on the beam ion slowing-down process during high-power neutral injection. Sawtooth oscillations were observed in the fast ion flux on PLT and PDX, and measurements with neutral beams providing local neutral density enhancement indicate that ions are transported radially when these events occur. With near-perpendicular injection in PDX, at the lower toroidal fields necessary to maximize beta, rapid, repetitive bursts of greatly enhanced charge-exchange flux were observed. These are associated with the ''fishbone'' MHD instability, and a substantial depletion of the perpendicular slowing-down spectrum below the injection energy was seen. A simple phenomenological model for this loss mechanism was developed, and its use in simulation codes has been successful in providing good agreement with the data. The behavior and characteristics of this model are well matched by the direct theoretical calculations

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

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Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Evaluation of serum prolidase activity and oxidative stress markers in men with BPH and prostate cancer.

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Kucukdurmaz, Faruk; Efe, Erkan; Çelik, Ahmet; Dagli, Hasan; Kılınc, Metin; Resim, Sefa

2017-12-12

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

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Lang Yi

2016-01-01

Full Text Available The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA patients, and healthy controls (HC in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28. In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Cutoff Values of Serum Carcinoembryonic Antigen (CEA) in Normal Korean Adults and Factors Influencing Serum CEA Level

International Nuclear Information System (INIS)

Kim, Jong Soon; Kim, Sun Wook; Chung, June Key; Lee, Dong Soo

1994-01-01

Carcinoembryonic Antigen is one of most frequently checked tumor markers in cancer management. We performed statistical analysis with serum CEA data of 2626 persons who received regular health examination and were thought to be free of active disease to determine the cutoff values of serum CEA level in normal Korean adults and to study the factors influencing serum CEA levels in normal subjects. 1) The cutoff values of serum CEA in normal Korean adults in general were 9.28 ng/ml for men, 5.90 ng/ml for women. 2) Serum CEA level was influenced by age, present smoking history, sex, and abnormal findings in chest X ray. 3) Serum CEA level had no correlation with the history of amount of alcohol consumption or obesity. 4) Cutoff values of serum CEA in normal Korean adults were tabulated according to age, sex, and smoking history. Serum CEA level was influenced by age, sex, present smoking history and abnormal findings in chest X ray and cutoff values of serum CEA were tabulated according to age, sex, and smoking history.

Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats.

Science.gov (United States)

Kading, Rebekah C; Kityo, Robert M; Mossel, Eric C; Borland, Erin M; Nakayiki, Teddie; Nalikka, Betty; Nyakarahuka, Luke; Ledermann, Jeremy P; Panella, Nicholas A; Gilbert, Amy T; Crabtree, Mary B; Peterhans, Julian Kerbis; Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Nichol, Stuart T; Powers, Ann M; Lutwama, Julius J; Miller, Barry R

2018-01-01

Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion:  Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats ( Epomophorus labiatus ) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

In Vivo Neutralization of α-Cobratoxin with High-Affinity Llama Single-Domain Antibodies (VHHs) and a VHH-Fc Antibody

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Richard, Gabrielle; Meyers, Ashley J.; McLean, Michael D.; Arbabi-Ghahroudi, Mehdi; MacKenzie, Roger; Hall, J. Christopher

2013-01-01

Small recombinant antibody fragments (e.g. scFvs and VHHs), which are highly tissue permeable, are being investigated for antivenom production as conventional antivenoms consisting of IgG or F(ab’)2 antibody fragments do not effectively neutralize venom toxins located in deep tissues. However, antivenoms composed entirely of small antibody fragments may have poor therapeutic efficacy due to their short serum half-lives. To increase serum persistence and maintain tissue penetration, we prepared low and high molecular mass antivenom antibodies. Four llama VHHs were isolated from an immune VHH-displayed phage library and were shown to have high affinity, in the low nM range, for α-cobratoxin (α–Cbtx), the most lethal component of Naja kaouthia venom. Subsequently, our highest affinity VHH (C2) was fused to a human Fc fragment to create a VHH2-Fc antibody that would offer prolonged serum persistence. After in planta (Nicotiana benthamiana) expression and purification, we show that our VHH2-Fc antibody retained high affinity binding to α–Cbtx. Mouse α–Cbtx challenge studies showed that our highest affinity VHHs (C2 and C20) and the VHH2-Fc antibody effectively neutralized lethality induced by α–Cbtx at an antibody:toxin molar ratio as low as ca. 0.75×:1. Further research towards the development of an antivenom therapeutic involving these anti-α-Cbtx VHHs and VHH2-Fc antibody molecules should involve testing them as a combination, to determine whether they maintain tissue penetration capability and low immunogenicity, and whether they exhibit improved serum persistence and therapeutic efficacy. PMID:23894495

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

Science.gov (United States)

Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

2013-01-01

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

Directory of Open Access Journals (Sweden)

Leticia Oliveira

Full Text Available A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients.TWO INDEPENDENT DEPRESSED SAMPLES: (1 Nineteen medication-free patients with depression and 19 healthy volunteers and (2 Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces using data only from healthy controls (HC. Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities for emotional and neutral face classification were different for healthy controls and depressed patients.Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1 and happy faces (samples 2 between depressed patients and healthy controls.Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This

Variation of serum and urine cotinine in passive and active smokers and applicability in preconceptional smoking cessation counseling

International Nuclear Information System (INIS)

Weerd, Sabina de; Thomas, Chris M.G.; Kuster, Josien E.T.G.; Cikot, Rolf J.L.M.; Steegers, Eric A.P.

2002-01-01

This study assessed the applicability of serum and urine cotinine as a biochemical marker of self-reported smoking habits for use in a preconception smoking cessation program. The variation of serum and urine cotinine over the course of the day was investigated in a sample of 21 smokers and 8 passive smokers who reported their smoking habits and exposure to smoke daily in a questionnaire for 10 consecutive days. Blood and urine samples were collected on two sampling days, 1 week apart. Both serum and urine cotinine assay could distinguish between passive and active smokers, but not between higher categories of smokers (1019 and ≥20 cigarettes per ay) due to significant intersubject overlap. In serum, no significant differences were found between morning and afternoon cotinine concentrations in either day, in contrast to urine cotinine (with lower excretions observed n the morning). An overall coefficient of variation of 22- was observed for both specimens in smokers. Because serum cotinine is subject to lower variability over the course of the day, it is more practical for use in a clinical setting where appointments are scheduled throughout the day in order o confirm smoking status

Effects of different levels of coconut fiber on blood glucose, serum insulin and minerals in rats.

Science.gov (United States)

Sindurani, J A; Rajamohan, T

2000-01-01

The effect of neutral detergent fiber (NDF) from coconut kernel (Cocos nucifera L) in rats fed 5%, 15% and 30% level on the concentration of blood glucose, serum insulin and excretion of minerals was studied. Increase in the intake of fiber resulted in significant decrease in the level of blood glucose and serum insulin. Faecal excretion of Cu, Cr, Mn, Mg, Zn and Ca was found to increase in rats fed different levels of coconut fiber when compared to fiber free group. The result of the present investigation suggest that inclusion of coconut fiber in the diet results in significant hypoglycemic action.

Head-out immersion in hot water increases serum BDNF in healthy males.

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Kojima, Daisuke; Nakamura, Takeshi; Banno, Motohiko; Umemoto, Yasunori; Kinoshita, Tokio; Ishida, Yuko; Tajima, Fumihiro

2017-11-20

Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations. Eight healthy men performed 20 min head-out water immersion at 42 °C (hot-HOI) and 35 °C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7 days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30 min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (T cb ) were measured. T cb was higher at the end of the hot-HOI and 15 min after hot-HOI (p hot-HOI. No change in T cb was recorded during neutral-HOI. BDNF level was higher (p hot-HOI and at 15 min after the end of hot-HOI, and returned to the baseline at 30 min after hot-HOI. S100β, platelet count and monocyte count remained stable throughout the study. Cortisol level was lower at the end of the hot-HOI and returned to pre-HOI level during the recovery period. BDNF and S100β, cortisol, and platelet and monocyte counts did not change throughout the neutral-HOI study. The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood-brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.

ACDOS1: a computer code to calculate dose rates from neutron activation of neutral beamlines and other fusion-reactor components

International Nuclear Information System (INIS)

Keney, G.S.

1981-08-01

A computer code has been written to calculate neutron induced activation of neutral-beam injector components and the corresponding dose rates as a function of geometry, component composition, and time after shutdown. The code, ACDOS1, was written in FORTRAN IV to calculate both activity and dose rates for up to 30 target nuclides and 50 neutron groups. Sufficient versatility has also been incorporated into the code to make it applicable to a variety of general activation problems due to neutrons of energy less than 20 MeV

Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population.

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Firouzabadi, Negar; Shafiei, Massoumeh; Bahramali, Ehsan; Ebrahimi, Soltan Ahmed; Bakhshandeh, Hooman; Tajik, Nader

2012-12-30

Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin-angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Detection of antibodies against H5 and H7 strains in birds: evaluation of influenza pseudovirus particle neutralization tests

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Sofie Wallerström

2014-01-01

Full Text Available Introduction: Avian influenza viruses circulate in bird populations, and it is important to maintain and uphold our knowledge of the viral strains that are currently of interest in this context. Here, we describe the use of hemagglutinin-pseudotype retroviruses based on highly pathogenic influenza viruses for the screening of avian sera for influenza A antibodies. Our aim was also to determine whether the pseudovirus neutralization tests that we assessed were sensitive and simple to use compared to the traditional methods, including hemagglutination inhibition assays and microneutralization tests. Material and methods: H5 and H7 pseudovirus neutralization tests were evaluated by using serum from infected rabbits. Subsequently, the assays were further investigated using a panel of serum samples from avian species. The panel contained samples that were seropositive for five different hemagglutinin subtypes as well as influenza A seronegative samples. Results and discussion: The results suggest that the pseudovirus neutralization test is an alternative to hemagglutination inhibition assays, as we observed comparable titers to those of both standard microneutralizations assays as well as hemagglutinin inhibition assays. When evaluated by a panel of avian sera, the method also showed its capability to recognize antibodies directed toward low-pathogenic H5 and H7. Hence, we conclude that it is possible to use pseudoviruses based on highly pathogenic avian influenza viruses to screen avian sera for antibodies directed against influenza A subtypes H5 and H7.

In vitro neutralization of the scorpion, Buthus tamulus venom toxicity.

Science.gov (United States)

Venkateswarlu, Y; Janakiram, B; Reddy, G R

1988-01-01

Scorpion (Buthus tamulus) venom was subjected to neutralization by treating the venom with various chemicals such as hydrochloric acid, sodium hydroxide, thiourea, formaldehyde, zinc sulphate, acetic acid and trichloroacetic acid. The venom was also subjected to heat treatment. The levels of total protein, free amino acids and protease activity in neutralized venom decreased significantly. The decrease in venom protein and free amino acids was in proportion to the duration of the heat treatment and the concentration of chemicals used except zinc sulphate, sodium hydroxide and thiourea. Protease activity of neutralized venom samples also showed a decrease except with zinc sulphate which enhanced the enzyme activity. Intramuscular injection of formaldehyde, trichlcroacetic acid and heat treated venoms into albino rats produced low mortality while thiourea and zinc sulphate were not effective in reducing the mortality. Hydrochloric acid and acetic acid treated venoms reduced the mortality by 50% with a decrease in the symptoms of envenomation. The changes were attributed to the denaturing of venom protein by chemical and heat treatments.

Validation of a serum neutralization test for detection of antibodies specific to cyprinid herpesvirus 3 in infected common and koi carp (Cyprinus carpio)

DEFF Research Database (Denmark)

Cabon, J.; Louboutin, L.; Castric, J.

2017-01-01

healthy and naturally or experimentally CyHV-3-infected carp. French CyHV-3 isolate 07/108b was neutralized efficiently by sera from carp infected with European, American and Taiwanese CyHV-3 isolates, but no neutralization was observed using sera specific to other aquatic herpesviruses. Diagnostic...

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children.

Science.gov (United States)

Broliden, K; Sievers, E; Tovo, P A; Moschese, V; Scarlatti, G; Broliden, P A; Fundaro, C; Rossi, P

1993-01-01

The prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression. PMID:8324904

Inhibitor of DNA synthesis is present in normal chicken serum

International Nuclear Information System (INIS)

Franklin, R.A.; Davila, D.R.; Westly, H.J.; Kelley, K.W.

1986-01-01

The authors have found that heat-inactivated serum (57 0 C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in 3 H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of 3 H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both 3 H-thymidine incorporation and IL-2 synthesis by Con A-activated murine splenocytes. Suppression was caused by actions other than cytotoxicity because viability of chicken splenocytes was unaffected by increasing levels of chicken serum. Furthermore, dialyzed serum retained its activity, which suggested that thymidine in the serum was not inhibiting uptake of radiolabeled thymidine. Suppressive activity was not due to adrenal glucocorticoids circulating in plasma because neither physiologic nor pharmacologic doses of corticosterone had inhibitory effects on mitogen-stimulated chicken splenocytes. These data demonstrate that an endogenous factor that is found in normal chicken serum inhibits proliferation of T-cells from chickens and mice as well as some transformed mammalian lymphoblastoid cell lines

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

Science.gov (United States)

Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

1984-03-01

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Concentration differences between serum and plasma of the elements cobalt, iron, mercury, rubidium, selenium and zinc determined by neutron activation analysis

International Nuclear Information System (INIS)

Kasperek, K.; Kiem, J.; Iyengar, G.V.; Feinendegen, L.E.

1981-01-01

The differences in concentrations of cesium, cobalt, iron, mercury, rubidium, selenium and zinc between serum and plasma were examined with the aid of instrumental neutron activation analysis. Eighty serum and plasma samples obtained from 13 donors were compared. Serum was prepared in plastic tubes immediately after clotting, and plasma was separated with heparin as anticoagulant. No significant differences in the concentrations of cesium, cobalt, mercury and selenium were observed. However, the concentrations of iron, rubidium and zinc were significantly higher in serum than in plasma. The average differences were 322, 12 and 20 ng/ml for iron, rubidium and zinc, respectively. The average differences found for cesium, rubidium and zinc were far below that which can be expected from a complete, or considerable release of these elements from platelets which aggregate or disintegrate during the clotting process in preparing serum. (orig.)

Effects of acute psychosocial stress on neural activity to emotional and neutral faces in a face recognition memory paradigm.

Science.gov (United States)

Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

2014-12-01

Previous studies have shown that acute psychosocial stress impairs recognition of declarative memory and that emotional material is especially sensitive to this effect. Animal studies suggest a central role of the amygdala which modulates memory processes in hippocampus, prefrontal cortex and other brain areas. We used functional magnetic resonance imaging (fMRI) to investigate neural correlates of stress-induced modulation of emotional recognition memory in humans. Twenty-seven healthy, right-handed, non-smoker male volunteers performed an emotional face recognition task. During encoding, participants were presented with 50 fearful and 50 neutral faces. One hour later, they underwent either a stress (Trier Social Stress Test) or a control procedure outside the scanner which was followed immediately by the recognition session inside the scanner, where participants had to discriminate between 100 old and 50 new faces. Stress increased salivary cortisol, blood pressure and pulse, and decreased the mood of participants but did not impact recognition memory. BOLD data during recognition revealed a stress condition by emotion interaction in the left inferior frontal gyrus and right hippocampus which was due to a stress-induced increase of neural activity to fearful and a decrease to neutral faces. Functional connectivity analyses revealed a stress-induced increase in coupling between the right amygdala and the right fusiform gyrus, when processing fearful as compared to neutral faces. Our results provide evidence that acute psychosocial stress affects medial temporal and frontal brain areas differentially for neutral and emotional items, with a stress-induced privileged processing of emotional stimuli.

Application of neutral electrolyzed water to disinfection of alginate impression.

Science.gov (United States)

Nagamatsu, Yuki; Chen, Ker-Kong; Nagamatsu, Hiroshi; Kozono, Yoshio; Shimizu, Hiroshi

2016-01-01

Neutral electrolyzed water was developed with new concepts of long-term good durability and minimum corrosiveness to metal in addition to its excellent bactericidal activities similar to acid type of electrolyzed waters. The present study examined the bactericidal effects of the neutral electrolyzed water on disinfection of the alginate impression of a dental arch model contaminated by bacteria. Only 1-min immersion in neutral electrolyzed water could sufficiently disinfect the alginate impression including the metallic tray under ultrasonic with no significant differences from acid electrolyzed waters. No bactericidal effects were found in any electrolyzed water when used as mixing water. Considering the advantages and disadvantages of each electrolyzed water in a comprehensive way, it was suggested that neutral electrolyzed water may be the most appropriate for the disinfection of alginate impression.

Neutral beam injector for 475 keV MARS sloshing ions

International Nuclear Information System (INIS)

Goebel, D.M.; Hamilton, G.W.

1983-01-01

A neutral beam injector system which produces 5 MW of 475 keV D 0 neutrals continuously on target has been designed. The beamline is intended to produce the sloshing ion distribution required in the end plug region of the conceptual MARS tandem mirror commercial reactor. The injector design utilizes the LBL self-extraction negative ion source and Transverse Field Focusing (TFF) accelerator to generate a long, ribbon ion beam. A laser photodetachment neutralizer strips over 90% of the negative ions. Magnetic and neutron shield designs are included to exclude the fringe fields of the end plug and provide low activation by the neutron flux from the target plasma. The use of a TFF accelerator and photodetachment neutralizer produces a total system electrical efficiency of about 63% for this design

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

Science.gov (United States)

Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhanced inflammation in New Zealand white rabbits when MERS-CoV reinfection occurs in the absence of neutralizing antibody.

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Katherine V Houser

2017-08-01

Full Text Available The Middle East respiratory syndrome coronavirus (MERS-CoV is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal infection, rabbits developed a transient dose-dependent pulmonary infection with moderately high levels of viral RNA, viral antigen, and perivascular inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed antibodies against viral proteins that lacked neutralizing activity and the animals were not protected from reinfection. In fact, reinfection resulted in enhanced pulmonary inflammation, without an associated increase in viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced inflammation upon infection. We further found this inflammation was accompanied by increased recruitment of complement proteins compared to primary infection. However, reinfection elicited neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a neutralizing antibody response, or persons whose neutralizing antibody titers have waned, may be at risk for severe lung disease on re-exposure to MERS-CoV.

A neutral sampling formula for multiple samples and an `exact' test of neutrality

NARCIS (Netherlands)

Etienne, R.S.

2007-01-01

As the utility of the neutral theory of biodiversity is increasingly being recognized, there is also an increasing need for proper tools to evaluate the relative importance of neutral processes (dispersal limitation and stochasticity). One of the key features of neutral theory is its close link to

A neutral sampling formula for multiple samples and an 'exact' test of neutrality

NARCIS (Netherlands)

Etienne, Rampal S.

As the utility of the neutral theory of biodiversity is increasingly being recognized, there is also an increasing need for proper tools to evaluate the relative importance of neutral processes (dispersal limitation and stochasticity). One of the key features of neutral theory is its close link to

Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis.

Science.gov (United States)

Kuusela, Elina; Kouri, Vesa-Petteri; Olkkonen, Juri; Koivuniemi, Riitta; Äyräväinen, Leena; Rajamäki, Kristiina; Valleala, Heikki; Nordström, Dan; Leirisalo-Repo, Marjatta; Ainola, Mari; Eklund, Kari K

2018-03-20

To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity. The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28). At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA. Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

Search for neutral leptons

International Nuclear Information System (INIS)

Perl, M.L.

1984-12-01

At present we know of three kinds of neutral leptons: the electron neutrino, the muon neutrino, and the tau neutrino. This paper reviews the search for additional neutral leptons. The method and significance of a search depends upon the model used for the neutral lepton being sought. Some models for the properties and decay modes of proposed neutral leptons are described. Past and present searches are reviewed. The limits obtained by some completed searches are given, and the methods of searches in progress are described. Future searches are discussed. 41 references

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

OpenAIRE

Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

1998-01-01

BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SA...

Neutral currents

International Nuclear Information System (INIS)

Paschos, E.A.

1977-01-01

It is stated that over the past few years considerable progress has been made in the field of weak interactions. The existence of neutral currents involving leptons and hadrons has been established and some of the questions concerning their detailed structure have been answered. This imposes constraints on the gauge theories and has eliminated large classes of models. New questions have also been raised, one of which concerns the conservation laws obeyed by neutral currents. The wide range of investigations is impressive and is expected to continue with new results from particle, nuclear, and atomic physics. Headings include - various aspects of a gauge theory (choice of group, the symmetry breaking scheme, representation assignments for fermion fields); space-time structure; isospin structure; leptonic neutral currents; and atomic experiments. (U.K.)

The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

Directory of Open Access Journals (Sweden)

Qunying Mao

Full Text Available EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics.In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246, were detected for neutralizing antibody (NTAb titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4.The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and the potential escape evolution for EV71 still need to

Serum lipase activity and concentration during intravenous infusions of GLP-1 and PYY3-36 and after ad libitum meal ingestion in overweight men

DEFF Research Database (Denmark)

Schmidt, Julie Berg; Sjödin, Anders Mikael; Stevner, Lene Susanne

2016-01-01

To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double-blinded, pl......To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double...... the infusion and after intake of an ad libitum meal for measurement of serum lipase. Serum lipase levels measured by enzyme-linked immunosorbent assay (ELISA) following mono-infusions of GLP-1 and PYY3-36 were comparable to serum lipase levels following placebo (P = 0.054 and P = 0.873, respectively......). Following the co-infusion of GLP-1 and PYY3-36, serum lipase levels measured by ELISA decreased over time compared to placebo (P = 0.012). However, the between-group difference was not consistent when each time point was analyzed separately. On the placebo day, serum lipase levels measured by ELISA after...

Stochastic demand patterns for Markov service facilities with neutral and active periods

International Nuclear Information System (INIS)

Csenki, Attila

2009-01-01

In an earlier paper, a closed form expression was obtained for the joint interval reliability of a Markov system with a partitioned state space S=U union D, i.e. for the probability that the system will reside in the set of up states U throughout the union of some specific disjoint time intervals I l =[θ l ,θ l +ζ l ],l=1,...,k. The deterministic time intervals I l formed a demand pattern specifying the desired active periods. In the present paper, we admit stochastic demand patterns by assuming that the lengths of the active periods, ζ l , as well as the lengths of the neutral periods, θ l -(θ l-1 +ζ l-1 ), are random. We explore two mechanisms for modelling random demand: (1) by alternating renewal processes; (2) by sojourn times of some continuous time Markov chain with a partitioned state space. The first construction results in an expression in terms of a revised version of the moment generating functions of the sojourns of the alternating renewal process. The second construction involves the probability that a Markov chain follows certain patterns of visits to some groups of states and yields an expression using Kronecker matrix operations. The model of a small computer system is analysed to exemplify the ideas

Reversible mode of binding of serum proteins to DOTAP/cholesterol Lipoplexes: a possible explanation for intravenous lipofection efficiency.

Science.gov (United States)

Simberg, Dmitri; Weiss, Aryeh; Barenholz, Yechezkel

2005-09-01

There are many indications that interaction of serum proteins with intravenously injected cationic lipoplexes disturbs lipofection in vitro and in vivo. However, transfection with certain lipid compositions such as N-[1- (2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol appears to be more resistant to serum and more efficacious. We investigated the mechanism of interaction between fluorescently labeled lipoplexes of the above composition and fluorescently labeled serum proteins. Fluorescence resonance energy transfer measurements in vitro indicate that serum proteins interact instantly and closely with the DOTAP/cholesterol lipoplexes. In accord with this, preinjection of fluorescently labeled serum into mice before injection of lipoplexes showed an immediate association of proteins with lipoplexes. Serum proteins colocalized with the lipoplexes in the lung vasculature; however, they dissociated from the cationic lipid as soon as 1 hr postinjection, probably because of displacement of serum proteins from lipoplexes by extracellular proteoglycans. Indeed, this displacement was imitated by heparin, a typical glycosaminoglycan, and could be explained by the inability of weakly acidic serum proteins to neutralize the DOTAP/cholesterol electrical surface potential psi0. The stability of the cationic lipid psi0 in serum could be a key reason for the high lung association and transfection efficiency with this formulation.

Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

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Jerome E. Tanner

2018-04-01

Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

Effect of bilirubin on the spectrophotometric and radionuclide assay for serum angiotensin-converting enzyme

International Nuclear Information System (INIS)

Saxe, A.W.; Hollinger, M.A.; Essam, T.

1986-01-01

The effect of bilirubin on serum angiotensin-converting enzyme (ACE) activity was studied with spectrophotometric and radionuclide assays. In the spectrophotometric assay addition of bilirubin to normal serum from dog, mouse, and human produced a dose-related inhibition of ACE activity. A 50% decrease in human ACE activity was produced by the addition of approximately 250 mg/L in vitro. Serum from icteric patients with elevated bilirubin was also associated with a reduction in ACE activity in the spectrophotometric assay. A 50% decrease in ACE activity in these samples was associated with a serum bilirubin of approximately 220 mg/L. In the radionuclide assay, however, addition of bilirubin to normal human serum failed to reduce measured ACE activity. The use of a radionuclide assay for serum ACE in clinical samples offers the advantage of less interference from serum bilirubin

E-ADA activity in serum of lambs experimentally infected with Haemonchus contortus.

Science.gov (United States)

Da Silva, Aleksandro S; Fausto, Guilherme C; Grando, Thirssa H; Cadore, Carlos A; Pimentel, Victor C; Jaques, Jeandre A; Schetinger, Maria R C; Monteiro, Silvia G; Leal, Marta L R

2013-08-01

The aim of this study was to evaluate adenosine deaminase (E-ADA) activity in sera of lambs experimentally infected with Haemonchus contortus. We used 12 lambs divided into 2 groups; Group A had 5 healthy, non-infected animals (control) and Group B had 7 healthy animals infected with H. contortus . Lambs were infected orally with 500 larvae (L3) per animal every 2 days, for a period of 20 days, and later the infection was confirmed by examination of feces (eggs per gram [EPG] via fecal egg count). Blood collection was performed at days 0, 20, 40, 60, and 80 post-infection (PI) for analysis of E-ADA activity. Animals in Group A showed negative EPG throughout the experiment unlike those from Group B that had elevated EPG counts. E-ADA activity was reduced in the serum of animals infected with H. contortus when compared to non-infected controls at days 20, 40, 60, and 80 PI. Therefore, it is concluded that infection with H. contortus influences the E-ADA activity in lambs.

Serum adenosine deaminase activity and its isoenzyme in patients treated for tuberculosis

International Nuclear Information System (INIS)

Rokayan, S.A

2003-01-01

Objective: Increased serum adenosine deaminase (ADA) activity, mainly associated with tuberculosis can also occur in a number of other diseases thus negatively affecting the diagnostic utility of ADA measurements in tuberculosis. The aim of the study was to determine whether or not the combined use of the activity of ADA, its isoenzymes and differential cell counts would provide a more efficient means of diagnosing tuberculosis than the use of ADA levels alone. Results: Data suggested significant (p 0.75) of ADA/sub 2/ADA was found to be better indicator of tuberculosis. Lymphocyte neutrophil ratio (L/N)> 0.69 gave additional benefit to increase the sensitivity and specificity for the use of ADA as marker in diagnosing tuberculosis. Conclusion: The combined use of activity of ADA, its isoenzymes and total and differential cell counts is a better indicator and gives better understanding to diagnose and evaluate tuberculosis and response to therapy. (author)

Effect of Thermospheric Neutral Density upon Inner Trapped-belt Proton Flux

Science.gov (United States)

Wilson, Thomas L.; Lodhi, M. A. K.; Diaz, Abel B.

2007-01-01

We wish to point out that a secular change in the Earth's atmospheric neutral density alters charged-particle lifetime in the inner trapped radiation belts, in addition to the changes recently reported as produced by greenhouse gases. Heretofore, changes in neutral density have been of interest primarily because of their effect on the orbital drag of satellites. We extend this to include the orbital lifetime of charged particles in the lower radiation belts. It is known that the charged-belt population is coupled to the neutral density of the atmosphere through changes induced by solar activity, an effect produced by multiple scattering off neutral and ionized atoms along with ionization loss in the thermosphere where charged and neutral populations interact. It will be shown here that trapped-belt flux J is bivariant in energy E and thermospheric neutral density , as J(E,rho). One can conclude that proton lifetimes in these belts are also directly affected by secular changes in the neutral species populating the Earth s thermosphere. This result is a consequence of an intrinsic property of charged-particle flux, that flux is not merely a function of E but is dependent upon density rho when a background of neutrals is present.

Serum protein inhibition of thyrotropin binding to human thyroid tissue

International Nuclear Information System (INIS)

Beall, G.N.; Chopra, I.J.; Solomon, D.H.; Kruger, S.R.

1978-01-01

We used a modificaton of the TSH radioreceptor assay to detect TSH-binding inhibition (TBI) activity in serum and serum fractions from normal subjects and patients with Graves' disease. TBI activity is present in normal IgG prepared by DEAE-Sephadex chromatography and in normal globulins prepared by precipitation at 1.6 M ammonium sulfate. Other normal serum proteins also had TBI activity when large concentrations were tested. Gel filtration chromatography and powder block electrophoresis were used to prepare fractions of normal and Graves' disease sera. In these fractions from normal serum, TBI activity was found in both γ-globulin and α-globulin-albumin fractions electrophoretically and in both 7S and 4S peaks from gel filtration. TBI activity from Graves' disease patients' sera was similarly distributed, but relatively more TBI accompanied the electrophoretic γ-globulins. Sepharose Protein-A and anti-IgG were used as immunoabsorbents to isolate and purify IgG from normal and Graves' disease sera. TBI activity in IgG was proportional to the IgG concentration, indicating that the TBI which migrates as a γ-globulin electrophoretically is an IgG and thus may possibly be an antibody. Inhibitory activity found in normal serum globulins and in the non-IgG fractions of both normal and abnormal sera seriously interferes with attempts to use the TSH radioreceptor assay to study the hypothesized anti-TSH receptor antibody in the serum of patients with Graves' disease

Plasma neutralizer for H- beams

International Nuclear Information System (INIS)

Grossman, M.W.

1977-01-01

Neutralization of H - beams by a hydrogen plasma is discussed. Optimum target thickness and maximum neutralization efficiency as a function of the fraction of the hydrogen target gas ionized is calculated for different H - beam energies. Also, the variation of neutralization efficiency with respect to target thickness for different H - beam energies is computed. The dispersion of the neutralized beam by a magnetic field for different energies and different values of B . z is found. Finally, a type of plasma jet is proposed, which may be suitable for a compact H - neutralizer

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

Science.gov (United States)

D'Eufemia, P; Finocchiaro, R; Zambrano, A; Lodato, V; Celli, L; Finocchiaro, S; Persiani, P; Turchetti, A; Celli, M

2017-01-01

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption

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Dietmar Enko

2016-01-01

Full Text Available The aim of this retrospective study was to analyze the concomitant prevalence rates for lactose malabsorption (LM, fructose malabsorption (FM, and histamine intolerance (HI in patients with so far unexplained gastrointestinal (GI symptoms. A total of 439 outpatients, who presented unclear abdominal discomfort, underwent lactose (50 g and fructose (25 g hydrogen (H2 breath tests. Additionally, serum diamine oxidase (DAO measurements were performed. Individuals with low serum DAO activity (<10 U/mL, GI symptoms, and response to histamine-free diet were diagnosed with HI. Of all 439 patients, 341 (77.7% were found with 7 various GI conditions. In total, 94 (21.4%, 31 (7.1%, and 100 (22.8% individuals presented LM, FM, or HI only, whereas 116 (26.4% patients showed an overlap of GI entities investigated here. Interestingly, 89 out of 241 (36.9% individuals with carbohydrate malabsorption were also diagnosed with HI (LM + HI: 52 [11.8%], FM + HI: 23 [5.2%], and LM + FM + HI 14 [3.2%] individuals. In conclusion different combinations of LM, FM, and HI are present in individuals with unclear abdominal discomfort/pain. In clinical practice we suggest testing for LM, FM, and additional HI in the diagnostic work-up of these patients. Depending on these various diagnoses possible, patients should get an individualized dietary advice.

Serum lysozyme determinations, April-June 1961

Energy Technology Data Exchange (ETDEWEB)

Finch, S C; Lamphere, J P; Jablon, S

1963-04-18

Serum lysozyme levels were determined on 670 consecutive subjects seen for regularly scheduled clinic examinations of the Adult Health Study in Hiroshima. Serum lysozyme levels were found to vary significantly with the absolute peripheral granulocyte count, age, sex, and month of study. A high level of correlation also was noted between serum lysozyme and diabetes mellitus. This was at least in part attributable to greater average age in patients with diabetes. Suggestive relationship was established between serum lysozyme levels, respiratory diseases, and tuberculosis. These changes are believed to reflect active inflammation with excessive destruction of granulocytes and parenchymal tissues in those patients with the more acute processes. No relationship was found between serum lysozyme and previous exposure to ionizing radiation. These studies indicate that the serum lysozyme level may be useful in the study of the kinetics of leukopoiesis, the aging process, and in the detection of subtle inflammatory processes. 21 references, 5 tables.

Effect of an ionizing radiation on the activity of the components of the system: DNA ase 1-natural DNA ase 1 inhibitor in blood serum of white rats

International Nuclear Information System (INIS)

Ivanova, A.B.; Kerova, N.I.; Pukhova, G.G.; Baraboj, V.A.; AN Ukrainskoj SSR, Kiev. Inst. Problem Onkologii)

1976-01-01

The presence of a natural inhibitor of DNAase 1 of protein nature is responsible for the inhibiting action of blood serum on pancreatic DNAase. Depending on the radiation dose (ranging from 450 to 750 R), the activity of the serum inhibitor of DNAase 1 increases for a short time, then, in the period from 15 minutes to 24 hours, it normalizes (450 R) or drastically decreases on the seventh day (750 R). At the dose of 750 R, the activity of free serum DNAase 1 increases throughout the entire period of the experiment; the activity of bound DNAase 1 gradually decreases and it is not observed on the seventh day. The dose of 450 R does not substantially affect the activity of free DNAase 1. Evidently, at high X-ray doses, formation of the inhibitor-serum DNAase 1 complex is disturbed

Serum levels of tumor necrosis factor-α and soluble adhesion molecules in relation to magnetic resonance imaging results and clinical activity in multiple sclerosis

International Nuclear Information System (INIS)

Millers, A.; Metra, M.; Mastina, M.; Platkajis, A.; Kukaine, R.

2001-01-01

One direction of research in pathogenesis of multiple sclerosis (MS) has been to identify immunological markers associated with disease activity that are capable of predicting subsequent course of disease and are sensitive to intervention by immunomodulatory therapies. Adhesion molecules and tumor necrosis factor-α of the cytokine superfamily are associated with inflammation-mediated blood-brain barrier dysfunction and demyelination in the central nervous system (CNS). This study investigates the relationship between the serum level of soluble vascular adhesion molecule-1 (sVCAM), soluble intercellular adhesion molecule-1 (alCAM), tumor necrosis factor-α (TNF-α) and magnetic resonance imaging (MRI) activity in 18 patients with relapsing-remitting (RR) MS with different clinical activity. Patients with active gadolinium (Gd)-enhanced lesions on MRI showed a higher serum level of TNF-α, sVCA-1, slCAM-1 than RR MS patients without Gd-enhanced lesions. Control individuals (n=10) without MRI abnormalities had significantly lower serum levels of the above immunological parameters. These results suggest that serum levels of TNF-α and adhesion molecules slCAM-1 in RR MS patients are correlated with Gd-enhanced MRI and disease clinical activity and that they can be used as biological markers of disease activity. The soluble form of VCAM levels in peripheral blood did not correlate with disease activity and Gd-enhanced lesions of MRI. sVCAM as an early indicator of blood-brain barrier dysfunction may also serve as marker of beneficial activity in the relapsing phase of MS course. (authors)

The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

Science.gov (United States)

Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

2014-01-01

To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

Radioimmunoassay of haloperidol in human serum: correlation of serum haloperidol with serum prolactin

International Nuclear Information System (INIS)

Poland, R.E.; Rubin, R.T.

1981-01-01

A radioimmunoassay (RIA) for measurement of serum haloperidol is described. Compared to gaschromatography (GC), RIA vaues average 40% higher. However, a simple organic extraction of serum yields statistically equivalent RIA and GC haloperidol determinations. For both men and women combined, there was a positive correlation between dose (mg/kg/day) and steady-state serum haloperidol level (r = +0.86) and between steady-state serum haloperidol and serum prolactin (PRL) concentration

Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus

International Nuclear Information System (INIS)

Stapleton, J.T.; Lemon, S.M.

1987-01-01

Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human convalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development

The Process of Separating Bovine Serum Albumin Using Hydroxyapatite and Active Babassu Coal (Orbignya martiana)

Science.gov (United States)

Zuñiga, Abraham Damian Giraldo; Sousa, Rita de Cássia Superbi; Zacchi Scolforo, Carmelita

2016-01-01

Bovine serum albumin is one of the major serum proteins; it plays an important role as a result of its functional and nutritional properties which have bioactive peptides. Adsorption method was used to separate protein, which involves hydroxyapatite, synthetic hydroxyapatite, and active babassu coal. Initially, characterization was carried out using the zeta potential of the adsorbents. Kinetic pseudo-first- and pseudo-second-order models were applied. For isotherms, equilibrium data studies were carried out using the Langmuir and Freundlich models, in addition to determining the efficiency of adsorptive process. The results of the zeta potential showed loads ranging from +6.9 to −42.8 mV. The kinetic data were better represented in the pseudo-second-order model with chemisorption characteristics. The adsorption capacity of the adsorbents decreased as pH increased, indicating that the electrostatic bonds and some functional groups of active babassu coal contributed to the reduction of adsorption, especially oxygen linked to carbon atoms. The value of pH 4.0 showed the best results of adsorption, being obtained as the maximum adsorption capacity (q m) and yield (%) (where q m = 87.95 mg g−1 and 74.2%; 68.26 mg g−1 and 68.6%; and 36.18 mg g−1, 37.4%) of hydroxyapatite, synthetic hydroxyapatite, and active babassu coal, respectively. PMID:27376149

Influence of Partial Neutralization on Catalytic Activity of Ion Exchange Resin

Czech Academy of Sciences Publication Activity Database

Holub, Ladislav; Jeřábek, Karel

2005-01-01

Roč. 231, 1-2 (2005), s. 21-26 ISSN 1381-1169 R&D Projects: GA ČR(CZ) GA104/02/1104 Institutional research plan: CEZ:AV0Z40720504 Keywords : catalysis * partial neutralization * polymer supports Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.348, year: 2005

On neutral plasma oscillations

International Nuclear Information System (INIS)

Shadwick, B.A.; Morrison, P.J.

1993-06-01

We examine the conditions for the existence of spectrally stable neutral modes in a Vlasov-Poisson plasma and show that for stable equilibria of systems that have unbounded spatial domain, the only possible neutral modes are those with phase velocities that correspond to stationary inflection points of the equilibrium distribution function. It is seen that these neutral modes can possess positive or negative free energy

On neutral plasma oscillations

International Nuclear Information System (INIS)

Shadwick, B.A.; Texas Univ., Austin; Morrison, P.J.; Texas Univ., Austin

1994-01-01

We examine the conditions for the existence of spectrally stable neutral modes in a Vlasov-Poisson plasma and show that for stable equilibria of systems that have unbounded spatial domain, the only possible neutral modes are those with phase velocities that correspond to stationary inflection points of the equilibrium distribution function. It is seen that these neutral modes can posses positive or negative free energy. (orig.)

Automated Facial Coding Software Outperforms People in Recognizing Neutral Faces as Neutral from Standardized Datasets

Directory of Open Access Journals (Sweden)

Peter eLewinski

2015-09-01

Full Text Available Little is known about people’s accuracy of recognizing neutral faces as neutral. In this paper, I demonstrate the importance of knowing how well people recognize neutral faces. I contrasted human recognition scores of 100 typical, neutral front-up facial images with scores of an arguably objective judge – automated facial coding (AFC software. I hypothesized that the software would outperform humans in recognizing neutral faces because of the inherently objective nature of computer algorithms. Results confirmed this hypothesis. I provided the first-ever evidence that computer software (90% was more accurate in recognizing neutral faces than people were (59%. I posited two theoretical mechanisms, i.e. smile-as-a-baseline and false recognition of emotion, as possible explanations for my findings.

Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity.

Science.gov (United States)

Inciarte-Mundo, José; Ramirez, Julio; Hernández, Maria Victoria; Ruiz-Esquide, Virginia; Cuervo, Andrea; Cabrera-Villalba, Sonia Raquel; Pascal, Mariona; Yagüe, Jordi; Cañete, Juan D; Sanmarti, Raimon

2016-07-08

Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 μg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.

First observations of partially neutralized and quasineutral plasmas in the Columbia Non-neutral Torus

Science.gov (United States)

Sarasola, Xabier; Brenner, Paul; Hahn, Michael; Pedersen, Thomas

2009-11-01

The Columbia Non-neutral Torus (CNT) is the first stellarator devoted to the study of pure electron, partially neutralized and positron-electron plasmas. To date, CNT usually operates with electron rich plasmas (with negligible ion density) [1], but a stellarator can also confine plasmas of arbitrary degree of neutralization. In CNT the accumulation of ions alters the equilibrium of electron plasmas and a global instability has been observed when the ion fraction exceeds 10 %. A characterization of this instability is presented in [2], analyzing its parameter dependence and spatial structure (non- resonant with rational surfaces). A new set of experiments is currently underway studying plasmas of arbitrary degree of neutralization, ranging from pure electron to quasineutral plasmas. Basic observations show that the plasma potential decouples from emitter bias when we increase the degree of the neutralization of our plasmas. Partially neutralized plasmas are also characterized by multiple mode behavior with dominant modes between 20 and 200 kHz. When the plasma becomes quasineutral, it reverts to single mode behavior. The first results on partially neutralized plasmas confined on magnetic surfaces will be presented. [1] J. Kremer, PRL 97, (2006) 095003 [2] Q. Marksteiner, PRL 100 (2008) 065002

Dual modifications strategy to quantify neutral and sialylated N-glycans simultaneously by MALDI-MS.

Science.gov (United States)

Zhou, Hui; Warren, Peter G; Froehlich, John W; Lee, Richard S

2014-07-01

Differences in ionization efficiency among neutral and sialylated glycans prevent direct quantitative comparison by their respective mass spectrometric signals. To overcome this challenge, we developed an integrated chemical strategy, Dual Reactions for Analytical Glycomics (DRAG), to quantitatively compare neutral and sialylated glycans simultaneously by MALDI-MS. Initially, two glycan samples to be compared undergo reductive amination with 2-aminobenzoic acid and 2-(13)[C6]-aminobenzoic acid, respectively. The different isotope-incorporated glycans are then combined and subjected to the methylamidation of the sialic acid residues in one mixture, homogenizing the ionization responses for all neutral and sialylated glycans. By this approach, the expression change of relevant glycans between two samples is proportional to the ratios of doublet signals with a static 6 Da mass difference in MALDI-MS and the change in relative abundance of any glycan within samples can also be determined. The strategy was chemically validated using well-characterized N-glycans from bovine fetuin and IgG from human serum. By comparing the N-glycomes from a first morning (AM) versus an afternoon (PM) urine sample obtained from a single donor, we further demonstrated the ability of DRAG strategy to measure subtle quantitative differences in numerous urinary N-glycans.

Plasma/Neutral-Beam Etching Apparatus

Science.gov (United States)

Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

1989-01-01

Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives

Science.gov (United States)

Matthews, Thomas J; Whittaker, Robert J

2014-01-01

Published in 2001, The Unified Neutral Theory of Biodiversity and Biogeography (UNTB) emphasizes the importance of stochastic processes in ecological community structure, and has challenged the traditional niche-based view of ecology. While neutral models have since been applied to a broad range of ecological and macroecological phenomena, the majority of research relating to neutral theory has focused exclusively on the species abundance distribution (SAD). Here, we synthesize the large body of work on neutral theory in the context of the species abundance distribution, with a particular focus on integrating ideas from neutral theory with traditional niche theory. First, we summarize the basic tenets of neutral theory; both in general and in the context of SADs. Second, we explore the issues associated with neutral theory and the SAD, such as complications with fitting and model comparison, the underlying assumptions of neutral models, and the difficultly of linking pattern to process. Third, we highlight the advances in understanding of SADs that have resulted from neutral theory and models. Finally, we focus consideration on recent developments aimed at unifying neutral- and niche-based approaches to ecology, with a particular emphasis on what this means for SAD theory, embracing, for instance, ideas of emergent neutrality and stochastic niche theory. We put forward the argument that the prospect of the unification of niche and neutral perspectives represents one of the most promising future avenues of neutral theory research. PMID:25360266

Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives.

Science.gov (United States)

Matthews, Thomas J; Whittaker, Robert J

2014-06-01

Published in 2001, The Unified Neutral Theory of Biodiversity and Biogeography (UNTB) emphasizes the importance of stochastic processes in ecological community structure, and has challenged the traditional niche-based view of ecology. While neutral models have since been applied to a broad range of ecological and macroecological phenomena, the majority of research relating to neutral theory has focused exclusively on the species abundance distribution (SAD). Here, we synthesize the large body of work on neutral theory in the context of the species abundance distribution, with a particular focus on integrating ideas from neutral theory with traditional niche theory. First, we summarize the basic tenets of neutral theory; both in general and in the context of SADs. Second, we explore the issues associated with neutral theory and the SAD, such as complications with fitting and model comparison, the underlying assumptions of neutral models, and the difficultly of linking pattern to process. Third, we highlight the advances in understanding of SADs that have resulted from neutral theory and models. Finally, we focus consideration on recent developments aimed at unifying neutral- and niche-based approaches to ecology, with a particular emphasis on what this means for SAD theory, embracing, for instance, ideas of emergent neutrality and stochastic niche theory. We put forward the argument that the prospect of the unification of niche and neutral perspectives represents one of the most promising future avenues of neutral theory research.

Trace element determination in fingernails, hair and blood serum in patients with Crohn's disease using neutron activation analysis

International Nuclear Information System (INIS)

Buschmann, H.

1984-01-01

The determination of trace elements and electrolyte concentrations in blood serum, hair and fingernails of 16 patients with Crohn's disease was carried out by means of instrumental neutron activation analysis. In the serum a significant decline in the zinc content could be registered, while the remaining trace elements remained in the normal range. The parenteral nutrition also showed a zinc deficiency. There was, however, also an iron deficiency. The studies of the hair and fingernails gave the following results: Rubidium and antimony in the normal range; zinc, selenium, iron and cobalt below normal values. (orig./PW) [de

Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

Directory of Open Access Journals (Sweden)

T. I. Bayeva

2016-09-01

Full Text Available In the article data are presented on dynamics of the level of indicators of metabolic profile of blood serum of race horses of the Ukrainian riding breed in the conditions of physical and emotional loading. Clinically healthy race horses were the object of  research. Blood was taken from the jugular vein to obtain serum and for further biochemical research. For the research 12 race horses from a training group were chosen. From time to time the animals took part in competitions; they were not specially used in races and were mostly used for the training of junior riders and sportsmen of different levels. Blood was taken in conditions of relative rest after ordinary training and after emotional stress during the entertainment performances when a large number of people were present and loud music was played. In the blood serum the following biochemical indicators were defined: whole protein, urea, creatinine, uric acid, total bilirubin and its fractions, glucose, cholestererol, triacylglycerol, calcium, ferrum, lactate, pyruvate, activity of the AlAT, SGOT, GGTP, LDH, an alkaline phosphatase – which makes it possible to determine reasonably accurately the adaptation potential of a horse under various types of loading. We established that during training and psychoemotional loading of racing horses of the training group of the Ukrainian riding breed, multidirectional changes in the level of biochemical indicators of blood serum occurred, which is evidence of stress in the metabolic processes in the animals’ organisms. Concentration of a biomarker of an oxidative stress, uric acid, increased after physical loading by 8.6%, and after emotional loading by 55.1%, which demonstrates that emotional stress had the more negative effect, indicating insufficient adaptation by the horses before demonstration performances. After physical loading, reaction of transamination in the horses’ liver cells intensified, and after emotional loading its intensity

Functional assay of the alternative complement pathway of rat serum

International Nuclear Information System (INIS)

Coonrod, J.D.; Jenkins, S.D.

1979-01-01

Two functional assays of the alternative pathway of complement activation in rat serum were developed. In the first assay, conditions were established for titration of alternative pathway activity by use of the 50% hemolytic end-point of rabbit red blood cells (RaRBC) in serum treated with ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA). The second assay of alternative pathway activity was based on the opsonization of heat-killed radiolabeled pneumococci of serotype 25 (Pn25). Opsonization of Pn25 was shown to proceed entirely via the alternative pathway in rat serum. There was excellent correlation between the results obtained with the RaRBC lysis test and those obtained with the opsonization test. Because of its technical simplicity, the RaRBC lysis test appeared to be the single most useful test of alternative pathway activity in rat serum. (Auth.)

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

Science.gov (United States)

Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

2006-01-01

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and

On plasma-neutral gas interaction

International Nuclear Information System (INIS)

Venkataramani, N.; Mattoo, S.K.

1980-01-01

The importance of plasma-neutral gas interaction layer has been emphasized by pointing out its application to a wide variety of physical phenomena. The interaction of a magnetised plasma stream penetrating a neutral gas cloud is discussed in the light of Alfven's critical velocity and Varma's threshold velocity on the ionising interaction. Interaction of a moving magnetised plasma with a stationary neutral gas has been studied and described. The device comprises of a plasma gun and an interaction region where neutral gas cloud is injected. The interaction region is provided with a transverse magnetic field of upto 1000 G. Several diagnostics deployed at the interaction region to make measurements on the macroscopic parameters of plasma and neutral gas are described. The parameters of discharge circuits are measured with high current and voltage probes. An interaction between a magnetised plasma stream and a neutral gas cloud is demonstrated. It is shown that this interaction does not have Varma's threshold on their relative velocity. The Alfven's critical velocity phenomenon is shown to depend on the integrated column neutral gas density that a plasma stream encounters while penetrating through it and not on the neutral gas density in the range of 10 17 -10 21 m -3 . (auth.)

Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

Science.gov (United States)

Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

2017-06-01

Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

Neutral current induced neutrino oscillations in a supernova

CERN Document Server

Kusenko, A; Kusenko, Alexander; Segre, Gino

1997-01-01

Neutral currents induced matter oscillations of electroweak-active (anti-)neutrinos to sterile neutrinos can explain the observed motion of pulsars. In contrast to a recently proposed explanation of the pulsar birth velocities based on the electron to tau (muon) neutrino oscillations [hep-ph/9606428], the heaviest neutrino (either active or sterile) would have to have mass of order several keV.

Is an inequality-neutral flat tax reform really neutral?

OpenAIRE

Juan Prieto Rodríguez; Juan Gabriel Rodríguez; Rafael Salas

2004-01-01

. Let us assume a revenue- and inequality-neutral flat tax reform shifting from a graduated-rate tax. Is this reform really neutral in terms of the income distribution? Traditionally, there has been a bias toward the inequality analysis, forgetting other relevant aspects of the income distribution. This kind of reforms implies a set of composite transfers, both progressive and regressive, even though inequality remains unchanged. This paper shows that polarization is a useful tool for charact...

Effect of ionising radiation and salt of cadmium on the activity enzymes in serum of chickens