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Sample records for anti human herpes

  1. Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy

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    Jacqueline Le Goaster

    2015-05-01

    Full Text Available In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.

  2. Genital herpes and human immunodeficiency virus: double trouble.

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    Celum, Connie; Levine, Ruth; Weaver, Marcia; Wald, Anna

    2004-01-01

    The synergistic relationship between herpes simplex virus type 2 (HSV-2) and transmission of human immunodeficiency virus (HIV) can be substantial in developing countries that have high prevalences of both viral infections. Genital herpes, most frequently caused by HSV-2, has become the leading cause of genital ulcer disease worldwide. This review of recent research on genital herpes and enhanced susceptibility to, and transmission of, HIV is part of the "Advances in HIV/AIDS research series"...

  3. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

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    M.O. Diniz

    2011-05-01

    Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  4. Impact of human herpes virus 6 in liver transplantation

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    Razonable, Raymund R.; Lautenschlager, Irmeli

    2010-01-01

    Human herpes virus 6 (HHV-6) infects > 95% of humans. Primary infection which occurs mostly during the first 2 years of life in the form of roseola infantum, non-specific febrile illness, or an asymptomatic illness, results in latency. Reactivation of latent HHV-6 is common after liver transplantation. Since the majority of human beings harbor the latent virus, HHV-6 infections after liver transplantation are most probably caused by endogenous reactivation or superinfection. In a minority of ...

  5. Lymphopaenia, anti-Ro/anti-RNP autoantibodies, renal involvement and cyclophosphamide use correlate with increased risk of herpes zoster in patients with systemic lupus erythematosus.

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    Hu, Stephen Chu-Sung; Lin, Chi-Ling; Lu, Yi-Wei; Chen, Gwo-Shing; Yu, Hsin-Su; Wu, Ching-Shuang; Lan, Cheng-Che E

    2013-05-01

    Herpes zoster occurs with increased frequency in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify and evaluate clinical and laboratory risk factors associated with development of herpes zoster in patients with SLE. A retrospective case-control study was performed in a population of patients with SLE. Patients were identified as cases if their first episode of herpes zoster occurred after diagnosis of SLE. Patients with SLE who never developed herpes zoster were enrolled as controls. Medical charts and laboratory data for both cases and control patients were comprehensively reviewed. A total of 65 cases and 105 controls were included. Risk factors associated with the development of herpes zoster in patients with SLE were found to be lymphopaenia, anti-Ro antibodies, anti-RNP antibodies, neuropsychiatric manifestations, renal involvement and cyclophosphamide use. Therefore, the presence of certain disease manifestations in patients with SLE represents risk factors for the development of herpes zoster.

  6. Evolutionary origins of human herpes simplex viruses 1 and 2.

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    Wertheim, Joel O; Smith, Martin D; Smith, Davey M; Scheffler, Konrad; Kosakovsky Pond, Sergei L

    2014-09-01

    Herpesviruses have been infecting and codiverging with their vertebrate hosts for hundreds of millions of years. The primate simplex viruses exemplify this pattern of virus-host codivergence, at a minimum, as far back as the most recent common ancestor of New World monkeys, Old World monkeys, and apes. Humans are the only primate species known to be infected with two distinct herpes simplex viruses: HSV-1 and HSV-2. Human herpes simplex viruses are ubiquitous, with over two-thirds of the human population infected by at least one virus. Here, we investigated whether the additional human simplex virus is the result of ancient viral lineage duplication or cross-species transmission. We found that standard phylogenetic models of nucleotide substitution are inadequate for distinguishing among these competing hypotheses; the extent of synonymous substitutions causes a substantial underestimation of the lengths of some of the branches in the phylogeny, consistent with observations in other viruses (e.g., avian influenza, Ebola, and coronaviruses). To more accurately estimate ancient viral divergence times, we applied a branch-site random effects likelihood model of molecular evolution that allows the strength of natural selection to vary across both the viral phylogeny and the gene alignment. This selection-informed model favored a scenario in which HSV-1 is the result of ancient codivergence and HSV-2 arose from a cross-species transmission event from the ancestor of modern chimpanzees to an extinct Homo precursor of modern humans, around 1.6 Ma. These results provide a new framework for understanding human herpes simplex virus evolution and demonstrate the importance of using selection-informed models of sequence evolution when investigating viral origin hypotheses.

  7. Human Herpes Virus Type 6 and Febrile Convulsion

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    HOUSHMANDI, Mohammad Mehdi; MOAYEDI, Alireza; Rahmati, Mohammad Bagher; NAZEMI, Abdulmajid; FAKHRAI, Darioush; ZARE, Shahram

    2015-01-01

    Objective Febrile Convulsion (FC) is occurred in 6 months to 5 yr old children. The aim of this study was to investigate the prevalence of HHV-6 infection in FC admitted patients of Bandar Abbas Children Hospital, southern Iran. Materials & Methods In a cross-sectional study, 118 children aged 6-60 months who had FC were selected by a simple random method in 2010-11. Demographic data, clinical manifestation and two blood samples gathered to assess the human herpes virus type 6 (HHV6). Blood s...

  8. Efficacy of the anti-VZV (anti-HSV3 vaccine in HSV1 and HSV2 recurrent herpes simplex disease: a prospective study

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    Le Goaster J

    2012-07-01

    Full Text Available Jacqueline Le Goaster,1 Sylvie Gonzalo,2 Patrice Bourée,1 Frederic Tangy,3 Anne-Lise Haenni41Department of Tropical Diseases, Centre Hospitalo-Universitaire (CHU, University of Paris XI, Le Kremlin Bicêtre, 2Biomnis Laboratory, Ivry-sur-Seine, 3Retro-Virology, Centre National de Recherche Scientifique (CNRS, Pasteur Institute, Paris; 4Jacques Monod Institute, Centre National de Recherche Scientifique (CNRS, University of Paris VII, Paris, FranceBackground: The aim of this study was to evaluate the possibility of using the anti-varicella zoster virus (anti-VZV, also known as anti-HSV3 vaccine against orobuccal herpes simplex virus type 1 (HSV1 and genital herpes simplex virus type 2 (HSV2. This was suggested by study of the phylogenetic tree of members of the herpes virus family, which showed a close relationship between VZV (HSV3 and the HSV1 and HSV2 herpes viruses.Methods: The present prospective study was conducted from January 2005 through January 2011. Twenty-four patients afflicted with HSV1 and HSV2 herpes recurrences over a period of years, numbering 6–8 and more recurrences per year, agreed to receive the anti-VZV vaccine. They were compared with 26 nonvaccinated patients presenting with herpes simplex diseases 2–5 times a year. All 50 patients were documented with anti-HSV1, anti-HSV2, and anti-VZV antibody serological testing.Results: From 2005 through 2011, for the 24 anti-VZV vaccinated patients, the average number of herpes relapses decreased to 0, correlated with an increased anti-VZV antibody level and clinical recovery of all patients, whereas no improvement was observed for the 26 nonvaccinated herpes patients.Conclusion: Data for the anti-VZV serological antibody levels tested before and after anti-VZV vaccination showed a significant (P < 0.001 increase among vaccinated patients. This suggests defective anti-VZV immune power in these patients. After 6 years of positive results for anti-VZV vaccine, this is a logical and

  9. Current Status of Natural Products from Plants as Anti-herpes Simplex Virus 1 Agents

    Institute of Scientific and Technical Information of China (English)

    Yang-fei XIANG; Ying PEI; Yi-fei WANG

    2008-01-01

    Nucleoside analogues have been the mainstay of clinical treatment of herpes simplex virus 1 (HSV-1) infections since their development. However, the emergence of drug resistant strains has underlined the urgency of the discovery of novel anti-HSV-1 drugs. Natural products, which provided many novel drug leads, are known to be an important source of anti-HSV-1 agents. Herein, we present an overview of natural products with anti-HSV-1 activities isolated from a variety of plants reported in recent years. Several different compounds, mainly belonging to the three groups of polysaccharides, polyphenols and terpenes, showed antiviral effects against HSV-1, indicating their potential to be promising anti-HSV-1 agents.

  10. Anti-herpes simplex virus activity of 5-substituted 2-pyrimidinone nucleosides.

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    Lewandowski, G A; Grill, S P; Fisher, M H; Dutschman, G E; Efange, S M; Bardos, T J; Cheng, Y C

    1989-01-01

    Several 5-substituted 2-pyrimidinone 2'-deoxyribonucleoside (PdR) analogs were examined for their anti-herpes simplex virus (HSV) activity in cell culture. The order of potency of their antiviral activities against HSV type 1 (HSV-1) and HSV-2 was iodo PdR approximately ethynyl PdR approximately propynyl PdR. The antiviral action of iodo PdR is dependent on the ability of HSV to induce virus-specified thymidine kinase in infected cells. Several HSV-1 variants with altered thymidine kinase cha...

  11. Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses.

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    Arnaud Chêne

    Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

  12. Isolation of a new herpes virus from human CD4 sup + T cells

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    Frenkel, N.; Schirmer, E.C.; Wyatt, L.S.; Katsafanas, G.; Roffman, E.; Danovich, R.M. (National Institutes of Health, Rockville, MD (USA)); June, C.H. (Naval Medical Research Institute, Bethesda, MD (USA))

    1990-01-01

    A new human herpes virus has been isolated from CD4{sup +} T cells purified from peripheral blood mononuclear cells of a healthy individual (RK), following incubation of the cells under conditions promoting T-cell activation. The virus could not be recovered from nonactivated cells. Cultures of lymphocytes infected with the RK virus exhibited a cytopathic effect, and electron microscopic analyses revealed a characteristic herpes virus structure. RK virus DNA did not hybridize with large probes derived from herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, and human cytomegalovirus. The genetic relatedness of the RK virus to the recently identified T-lymphotropic human herpes virus 6 (HHV-6) was investigated by restriction enzyme analyses using 21 different enzymes and by blot hydridization analyses using 11 probes derived from two strains of HHV-6 (Z29 and U1102). Whereas the two HHV-6 strains exhibited only limited restriction enzyme polymorphism, cleavage of the RK virus DNA yielded distinct patterns. Of the 11 HHV-6 DNA probes tested, only 6 cross-hybridized with DNA fragments derived from the RK virus. Taken together, the maximal homology amounted to 31 kilobases of the 75 kilobases tested. The authors conclude that the RK virus is distinct from previously characterized human herpesviruses. The authors propose to designate it as the prototype of a new herpes virus, the seventh human herpes virus identified to date.

  13. In vitro evaluation of anti-herpes simplex-1 activity of three standardized medicinal plants from Lamiaceae

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    Mehdi Ansari; Fariba Sharififar; Ali Mohammad Arabzadeh; Firoozeh Mehni; Manosur Mirtadzadini; Zahra Iranmanesh; Najmeh Nikpour

    2014-01-01

    Background: Rosmarinic acid (RA) is a phenolic acid with antioxidant and anti-viral effects. We have studied anti-herpes simplex virus type 1 (HSV-1) effect of three medicinal plants from Lamiaceae family which have been standardized on the basis of RA content. Materials and Methods: Methanolic extract of Teucrium polium, Ziziphora clinopoides, and Salvia rhytidea was prepared by maceration method and RA content of the plants was determined using a spectrophotometric method. Maximum nonto...

  14. Oncolytic herpes simplex virus vectors for the treatment of human breast cancer

    Institute of Scientific and Technical Information of China (English)

    LIU Ren-bin; Samuel D.Rabkin

    2005-01-01

    Background Oncolytic herpes simplex virus (HSV) vectors can be used for cancer therapy as direct cytotoxic agents, inducers of anti-tumor immune responses, and as expressers of anti-cancer genes. In this study, the efficacy of HSV vectors, G47Δ and NV1023 were examined for the treatment of the human breast cancer.Methods Human breast cancer MDA-MB-435 cells were cultured or implanted subcutaneously in BALB/c nude mice. The cells or tumors were inoculated with G47Δ or NV1023, and cell killing or inhibition of tumor growth determined. Both viruses contained the LacZ gene and expression in infected cells was detected with X-gal histochemistry. Results G47Δ and NV1023 were highly cytotoxic to MDA-MB-435 cells in vitro at very low multiplicities of infection. X-gal staining of infected tumor cells in vitro and in vivo illustrated the replication and spread of both viruses. G47Δ and NV1023 inoculation inhibited tumor growth and prolonged mouse survival. Both vectors behaved similarly.Conclusions Oncolytic HSV vectors, G47Δ and NV1023, were extremely effective at killing human breast cancer cells in vitro and in tumor xenografts in vivo. This novel form of cancer therapy warrants further investigation and consideration of clinical application.

  15. Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study

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    Guti??rrez-Fern??ndez, Jos??; Luna Del Castillo, Juan De Dios; Ma??anes-Gonz??lez, Sara; Carrillo-??vila, Jos?? Antonio; Guti??rrez, Blanca; Cervilla, Jorge A; Sorl??zano Puerto, Antonio

    2015-01-01

    In the present study we have performed both a meta-analysis and an analytical study exploring the presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii antibodies in a sample of 143 schizophrenic patients and 143 control subjects. The meta-analysis was performed on papers published up to April 2014. The presence of serum immunoglobulin G and immunoglobulin A was performed by enzyme-linked immunosorbent assay test. The detection of microbial...

  16. Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides.

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    Janwitayanuchit, Wicharn; Suwanborirux, Khanit; Patarapanich, Chamnan; Pummangura, Sunibhond; Lipipun, Vimolmas; Vilaivan, Tirayut

    2003-12-01

    Based on the discovery of antiviral beta-galactosyl diglycerides from Clinacanthus nutans leaves, 19 monoglycosyl diglycerides were synthesized and examined for inhibitory effect on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). A study of the structure-activity relationships of the synthetic monoglycosyl diglycerides indicated that the fatty acyl moieties were critical for inhibitory action with higher activity displayed as the acyl groups became more olefinic in character. The sugar moiety was also important for anti-HSV action; however, the type of sugar (glucose or galactose) did not affect activity. The stereochemistry at C-2 of the glycerol backbone displayed no significant effect on anti-HSV activity. Among the compounds synthesized, 1,2-O-dilinolenoyl-3-O-beta-D-glucopyranosyl-sn-glycerol showed the highest inhibitory activity against HSV-1 and HSV-2 with IC50 values of 12.5+/-0.5 and 18.5+/-1.5 microg/ml, respectively. PMID:14599523

  17. A comparison of herpes simplex virus plaque development after viral treatment with anti-DNA or antilipid agents.

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    Coohill, T P; Babich, M; Taylor, W.D.; Snipes, W

    1980-01-01

    The plaque development of Herpes simplex virus type 1 (HSV) is slower for viruses treated with two anti-DNA agents: ultraviolet radiation (UV) or n-acetoxy-2-acetyl-aminofluorene. For HSV treated with three antimembrane agents--butylated hydroxytoluene, acridine plus near UV radiation, or ether--the plaque development time is the same as for untreated viruses. These differences hold even for viruses that survived treatment that lowered viability below the 1% level. Gamma ray inactivation of H...

  18. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

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    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  19. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    International Nuclear Information System (INIS)

    Research highlights: → We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. → Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. → Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7-/- cells (autophagy-defective cells) derived from an atg7-/- knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  20. Relation between disease modifying anti-rheumatic drugs and herpes zoster in rheumatoid arthritis.

    Science.gov (United States)

    Yamaoka, Kunihiro

    2016-01-01

      Biologics have revolutionized the treatment of rheumatoid arthritis (RA). However certain amount of the patients cannot achieve goal of therapy. Recently, compounds targeting the intracellular kinase, Janus kinase (JAK) have demonstrated therapeutic effects resembling biologics. Tofacitinib is the only JAK inhibitor approved for RA and during the clinical trial, increased events of herpes zoster (HZ) was observed. Incidence rate was twice as much as patients treated with conventional anti-rheumatic drug and was especially increased in Japan that was four times as much. The risk factors were age and glucocorticoid that is identical to that of common RA patients and there was nothing specific for tofacitinib. Mechanism of increased incidence of HZ and the difference in ethnicity remains unknown. Analysis of clinical trials have identified that HZ do not correlate with further adverse events. Therefore, it is extremely important to accumulate clinical data with considerable amount of patients with long term follow up including the post marketing surveillance in Japan to reveal the significance of increased HZ in RA patients. PMID:27320933

  1. Herpes viruses and human papilloma virus in nasal polyposis and controls

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    Dimitrios Ioannidis

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

  2. Herpes - resources

    Science.gov (United States)

    Genital herpes - resources; Resources - genital herpes ... The following organizations are good resources for information on genital herpes : March of Dimes -- www.marchofdimes.com/pregnancy/complications-herpes National Institute of Allergy and Infectious Disease -- ...

  3. The identities and anti-herpes simplex virus activity of Clinacanthusnutans and Clinacanthus siamensis

    Institute of Scientific and Technical Information of China (English)

    Paween Kunsorn; Nijsiri Ruangrungsi; Vimolmas Lipipun; Ariya Khanboon; Kanchana Rungsihirunrat

    2013-01-01

    Objective: To distinguish the difference among the Clinacanthus nutans (Burm. f.) Lindau (C. nutans) and Clinacanthus siamensis Bremek (C. siamensis) by assessing pharmacognosy characteristics, molecular aspect and also to evaluate their anti-herpes simplex virus (HSV) type 1 and type 2 activities. Methods: Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline. Stomatal number, stomatal index and palisade ratio of leaves were evaluated. Genomic DNA was extracted by modified CTAB method and ITS region was amplified using PCR and then sequenced. Dry leaves were subsequently extracted withn-hexane, dichloromethane and methanol and antiviral activity was performed using plaque reduction assay and the cytotoxicity of the extracts on Vero cells was determined by MTT assay. Results: Cross section of midrib and stem showed similar major components. Leaf measurement index of stomatal number, stomatal index and palisade ratio of C. nutans were 168.32±29.49, 13.83±0.86 and 6.84±0.66, respectively, while C. siamensis were 161.60±18.04, 11.93±0.81 and 3.37±0.31, respectively. The PCR amplification of ITS region generated the PCR product approximately 700 bp in size. There were 34 polymorphisms within the ITS region which consisted of 11 Indels and 23 nucleotide substitutions. The IC50 values of C. nutans extracted with n-hexane, dichloromethane and methanol against HSV-1 were (32.05±3.63) µg/mL, (44.50±2.66) µg/mL, (64.93±7.00) µg/mL, respectively where as those of C. siamensis were (60.00±11.61) µg/mL, (55.69±4.41) µg/mL, (37.39±5.85) µg/mL, respectively. Anti HSV-2 activity of n-hexane, dichloromethane and methanolC. nutans leaves extracts were (72.62±12.60) µg/mL, (65.19±21.45) µg/mL, (65.13±2.22) µg/mL, respectively where as those of C. siamensis were (46.52±4.08) µg/mL, (49.63±2.59) µg/mL, (72.64±6.52) µg/mL, respectively. Conclusions: The combination of macroscopic, microscopic and biomolecular method are

  4. Comparison of Herpes simplex virus plaque development after viral treatment with anti-DNA or antilipid agents

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    Coohill, T.P.; Babich, M.; Taylor, W.D.; Snipes, W.

    1980-06-01

    The plaque development of Herpes simplex virus type 1 (HSV) is slower for viruses treated with two anti-DNA agents: ultraviolet radiation (uv) or n-acetoxy-2-acetyl-aminofluorene. For HSV treated with three antimembrane agents - butylated hydroxytoluene, acridine plus near uv radiation, or ether - the plaque development time is the same as for untreated viruses. These differences hold even for viruses that survived treatment that lowered viability below the 1% level. Gamma ray inactivation of HSV produces no change in plaque development even though this agent is believed to preferentially affect viral DNA.

  5. Characterization of anti-herpes simplex virus type 1 activity of an alkaloid FK 3000 from Stephania cepharantha

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    Hattori, Masao; Ohsaki, Motoki; Kurokawa, Masahiko; NAWAWI, As'ari; Nakamura, Norio; Shiraki, Kimiyasu

    2002-01-01

    A morphinane alkaloid FK 3000 (6,7-di-O-acetylsinococuline) from the root tubers of Stephania cepharantha showed antiviral activity against acyclovir (ACV)- and phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1), influenza virus, measles virus, and poliovirus. The anti-HSV action of FK 3000 was assessed in comparison with that of PAA that inhibits the activity of HSV DNA polymerase and HSV DNA synthesis. FK 3000 inhibited the growth of thymidine kinase-deficient and ACV ...

  6. Herpes simplex virus-mediated human hypoxanthine-guanine phosphoribosyltransferase gene transfer into neuronal cells

    Energy Technology Data Exchange (ETDEWEB)

    Palella, T.D.; Silverman, L.J.; Schroll, C.T.; Homa, F.L.; Levine, M.; Kelley, W.N.

    1988-01-01

    The virtually complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, Lesch-Nyhan syndrome. Transfer of the HPRT gene into fibroblasts and lymphoblasts in vitro and into hematopoietic cells in vivo has been accomplished by other groups with retroviral-derived vectors. It appears to be necessary, however, to transfer the HPRT gene into neuronal cells to correct the neurological dysfunction of this disorder. The neurotropic virus herpes simplex virus type 1 has features that make it suitable for use as a vector to transfer the HPRT gene into neuronal tissue. This report describes the isolation of an HPRT-deficient rat neuroma cell line, designated B103-4C, and the construction of a recombinant herpes simplex virus type 1 that contained human HPRT cDNA. These recombinant viruses were used to infect B103-4C cells. Infected cells expressed HPRT activity which was human in origin.

  7. Suspected chromosomally integrated human herpes virus 6 in hematopoietic stem cell transplantation

    OpenAIRE

    Anna Todisco; Maria Landi; Beatrice Paola Festa; Lidia Santoro; Gabriella Storti; Giulia Campanini; Raffaele Ariola; Franca Romeo; Generoso Violano

    2016-01-01

    Background and aims: We report a case of a 27-year-old male affected by acute myeloid leukaemia MLL-PTD positive. After autologous stem cell transplantation, he was monitored based on cytomegalovirus, Epstein-Barr virus and human herpes virus 6 (HHV-6) DNA quantification in blood. Relapse occurred one year after transplantation; then the patient underwent to allogenic bone marrow transplantation using genotypically HLA-identical donor (sister). HHV-6 DNAemia was positive and persistently elev...

  8. Synergistic effect of human leukocyte interferon and nonoxynol 9 against herpes simplex virus type 2.

    OpenAIRE

    Rapp, F; Wrzos, H

    1985-01-01

    The nonionic surfactant nonoxynol 9 (NP9), in combination with human alpha interferon, synergistically reduced the titer of herpes simplex virus type 2 (HSV-2) in vitro. The degree of synergy was highest at an interferon concentration of 10(3) IU/ml and an NP9 dilution of 1:1,500. We postulate that NP9 inactivates extracellular HSV-2, whereas interferon inhibits HSV-2 replication at the intracellular level.

  9. Human antibody response to herpes simplex virus-specific polypeptides after primary and recurrent infection.

    OpenAIRE

    Kahlon, J; Lakeman, F. D.; Ackermann, M; Whitley, R J

    1986-01-01

    Human antibody responses to specific polypeptides of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) were assessed in serial serum specimens from 18 infected patients by immunoblot technology. Nine patients had HSV-1 infections (six genital and three oral) and nine had HSV-2 genital infections. Antibodies to homologous and heterologous HSV antigens were studied and correlated with total microneutralization and enzyme-linked immunosorbent assay antibodies as well as correlat...

  10. A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity.

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    Full Text Available Oncolytic viruses are promising treatments for many kinds of solid tumors. In this study, we constructed a novel oncolytic herpes simplex virus type 2: oHSV2. We investigated the cytopathic effects of oHSV2 in vitro and tested its antitumor efficacy in a 4T1 breast cancer model. We compared its effect on the cell cycle and its immunologic impact with the traditional chemotherapeutic agent doxorubicin. In vitro data showed that oHSV2 infected most of the human and murine tumor cell lines and was highly oncolytic. oHSV2 infected and killed 4T1 tumor cells independent of their cell cycle phase, whereas doxorubicin mainly blocked cells that were in S and G2/M phase. In vivo study showed that both oHSV2 and doxorubicin had an antitumor effect, though the former was less toxic. oHSV2 treatment alone not only slowed down the growth of tumors without causing weight loss but also induced an elevation of NK cells and mild decrease of Tregs in spleen. In addition, combination therapy of doxorubicin followed by oHSV2 increased survival with weight loss than oHSV2 alone. The data showed that the oncolytic activity of oHSV2 was similar to oHSV1 in cell lines examined and in vivo. Therefore, we concluded that our virus is a safe and effective therapeutic agent for 4T1 breast cancer and that the sequential use of doxorubicin followed by oHSV2 could improve antitumor activity without enhancing doxorubicin's toxicity.

  11. The identities and anti-herpes simplex virus activity of Clinacanthus nutans and Clinacanthus siamensis

    Institute of Scientific and Technical Information of China (English)

    Paween; Kunsorn; Nijsiri; Ruangrungsi; Vimolmas; Lipipun; Ariya; Khanboon; Kanchana; Rungsihirunrat

    2013-01-01

    Objective:To distinguish the difference among the Clinacanthus nutans(Burm.f.)Lindau(C.nutans)and Clinacanthus siamensis Bremek(C.siamensis)by assessing pharmacognosy characteristics,molecular aspect and also to evaluate their anti-herpes simplex virus(HSV)type 1 and type 2 activities.Methods:Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline.Stomatal number,stomatal index and palisade ratio of leaves were evaluated.Genomic DNA was extracted by modified CTAB method and ITS region was amplified using PGR and then sequenced.Dry leaves were subsequently extracted with n-hexane,dichloromethane and methanol and antiviral activity was performed using plaque reduction assay and the cytotoxicity of the extracts on Vero cells was determined by MTT assay.Results:Cross section of midrib and stem showed similar major components.Leaf measurement index of stomatal number,stomatal index and palisade ratio of C.nutans were 168.32±29.49,13.83±0.86 and 6.84±0.66,respectively,while C.siamensis were 161.60±18.04,11.93±0.81and 3.37±0.31,respectively.The PCR amplification of ITS region generated the PGR product approximately 700 bp in size.There were 34 polymorphisms within the ITS region which consisted of 11 Indels and 23 nucleotide substitutions.The IC50values of C.nutans extracted with n-hexane,dichloromethane and methanol against HSV-1 were(32.05±3.63)μg/mL,(44.50±2.66)μg/mL,(64.93±7.00)μg/mL,respectively where as those of C.siamensis were(60.00±11.61)μg/mL,(55.69+4.41)μg/mL,(37.39±5.85)μg/mL,respectively.Anti HSV-2 activity of n-hexane,dichloromethane and methanol C.nutans leaves extracts were(72.62±12.60)μg/mL,(65.19±21.45)μg/mL,(65.13±2.22)μg/mL,respectively where as those of C.siamensis were(46.52±4.08)μg/mL,(49.63±2.59)μg/mL,(72.64±6.52)μg/mL,respectively.Conclusions:The combination of macroscopic,microscopic and biomolecular method are able to

  12. No evidence of parvovirus B19, Chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis

    DEFF Research Database (Denmark)

    Helweg-Larsen, J; Tarp, B; Obel, N;

    2002-01-01

    OBJECTIVES: Recent studies have suggested that infective agents may be involved in the pathogenesis of giant cell arteritis (GCA), in particular Chlamydia pneumoniae and parvovirus B19. We investigated temporal arteries from patients with GCA for these infections as well as human herpes viruses...... conditions. DNA was extracted from frozen biopsies and PCR was used to amplify genes from Chlamydia pneumoniae, parvovirus B19 and each of the eight human herpes viruses: herpes simplex viruses HSV-1 and 2, Epstein-Barr virus, cytomegalovirus, varicella zoster virus and human herpes viruses HHV-6, -7 and -8....... RESULTS: In all 30 biopsies, PCR was negative for DNAs of parvovirus B19, each of the eight human herpes viruses and C. pneumoniae. CONCLUSIONS: We found no evidence of DNA from parvovirus B19, human herpes virus or C. pneumoniae in any of the temporal arteries. These agents do not seem to play a unique...

  13. Preliminary study on Herpes simplex virus type 1 infection of human oral epithelial cell in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhao; Weibin Sun; Juan Wang

    2008-01-01

    Objective: To explore the functions and mechanisms of herpes simplex virus type 1(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Veto cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results:The infected human oral epithelial cells didn't display an obvious cytopathic effect(CPE) under inverted microscope(while Veto cells which were infected by the culture supematant showed typical(CPE). The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion:HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.

  14. Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.

    Science.gov (United States)

    Sasaki, Hiroaki; Maeda, Takuya; Hara, Yu; Osa, Morichika; Imai, Kazuo; Moriguchi, Kota; Mikita, Kei; Fujikura, Yuji; Kaida, Kenichi; Kawana, Akihiko

    2015-10-01

    We report a case of human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman's disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman's disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load. PMID:25504830

  15. Epidemiology of Herpes Human Virus 6 and 7 Infections in Salivary Gland Neoplasms in Isfahan, Iran

    OpenAIRE

    Shanehsazzadeh, Mehrnaz; Rad, Javad Sharifi-; Pourazar, Abbasali; Behbahani, Mandana

    2014-01-01

    Background: The previous studies showed that herpes human virus-6 (HHV-6) and HHV-7 exist in salivary glands. One of the important areas in oral and maxillofacial pathology field is tumors of the salivary glands. In this study, to declare the major sites of persistent infection with HHV-6 and HHV-7, the existence of HHV-6 and HHV-7 genomes in formalin-fixed paraffin embedded tissue samples of salivary gland tumors. Methods: This analytical study was performed in 60 paraffin blocks samples of ...

  16. The Link between Hypersensitivity Syndrome Reaction Development and Human Herpes Virus-6 Reactivation

    Directory of Open Access Journals (Sweden)

    Joshua C. Pritchett

    2012-01-01

    Data Sources and Extraction. Drugs identified as causes of (i idiosyncratic reactions, (ii drug-induced hypersensitivity, drug-induced hepatotoxicity, acute liver failure, and Stevens-Johnson syndrome, and (iii human herpes virus reactivation in PubMed since 1997 have been collected and discussed. Results. Data presented in this paper show that HHV-6 reactivation is associated with more severe organ involvement and a prolonged course of disease. Conclusion. This analysis of HHV-6 reactivation associated with drug-induced severe cutaneous reactions and hepatotoxicity will aid in causality assessment and clinical diagnosis of possible life-threatening events and will provide a basis for further patient characterization and therapy.

  17. Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease

    OpenAIRE

    Flores, Sonia C.; Almodovar, Sharilyn

    2013-01-01

    The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endoth...

  18. Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin.

    Directory of Open Access Journals (Sweden)

    Min Kim

    2015-04-01

    Full Text Available The mechanism by which immunity to Herpes Simplex Virus (HSV is initiated is not completely defined. HSV initially infects mucosal epidermis prior to entering nerve endings. In mice, epidermal Langerhans cells (LCs are the first dendritic cells (DCs to encounter HSV, but it is CD103(+ dermal DCs that carry viral antigen to lymph nodes for antigen presentation, suggesting DC cross-talk in skin. In this study, we compared topically HSV-1 infected human foreskin explants with biopsies of initial human genital herpes lesions to show LCs are initially infected then emigrate into the dermis. Here, LCs bearing markers of maturation and apoptosis formed large cell clusters with BDCA3(+ dermal DCs (thought to be equivalent to murine CD103(+ dermal DCs and DC-SIGN(+ DCs/macrophages. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages and the BDCA3(+ dermal DCs had up-regulated a damaged cell uptake receptor CLEC9A. No other infected epidermal cells interacted with dermal DCs. Correspondingly, LCs isolated from human skin and infected with HSV-1 in vitro also underwent apoptosis and were taken up by similarly isolated BDCA3(+ dermal DCs and DC-SIGN(+ cells. Thus, we conclude a viral antigen relay takes place where HSV infected LCs undergo apoptosis and are taken up by dermal DCs for subsequent antigen presentation. This provides a rationale for targeting these cells with mucosal or perhaps intradermal HSV immunization.

  19. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G;

    2005-01-01

    Kaposi's sarcoma (KS)-associated herpesvirus or human herpes virus 8 is considered the etiological agent of KS, a highly vascularized neoplasm that is the most common tumor affecting HIV/AIDS patients. The KS-associated herpesvirus/human herpes virus 8 open reading frame 74 encodes a constitutively...... active G protein-coupled receptor known as vGPCR that binds CXC chemokines with high affinity. In this study, we show that conditional transgenic expression of vGPCR by cells of endothelial origin triggers an angiogenic program in vivo, leading to development of an angioproliferative disease...

  20. Lichen planus remission is associated with a decrease of human herpes virus type 7 protein expression in plasmacytoid dendritic cells

    NARCIS (Netherlands)

    H.J.C. de Vries; M.B.M. Teunissen; F. Zorgdrager; D. Picavet; M Cornelissen

    2007-01-01

    The cause of lichen planus is still unknown. Previously we showed human herpes virus 7 (HHV-7) DNA and proteins in lesional lichen planus skin, and significantly less in non-lesional lichen planus, psoriasis or healthy skin. Remarkably, lesional lichen planus skin was infiltrated with plasmacytoid d

  1. Genital Herpes

    Science.gov (United States)

    ... genital herpes infection occur? The herpes virus can pass through a break in your skin during vaginal, oral, or anal sex. It can ... their secretions do not touch the other person’s skin. Wash your hands with soap ... is possible for you to pass herpes to someone else even when you do ...

  2. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    Science.gov (United States)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  3. Human Herpes Virus Type 2 (HSV2), Human Cytomegalovirus (HCMV) in the Male Genital Tract and Fertilization

    Institute of Scientific and Technical Information of China (English)

    Courtot Anne Marie; Pallier Coralie; Testart Jacques

    2003-01-01

    The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.

  4. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

    DEFF Research Database (Denmark)

    Christensen, Tove

    2005-01-01

    may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and...

  5. Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Xuan Lu; Dao-Zhen Chen; Shu-Feng Li; Li-Shan Zhang

    2004-01-01

    AIM: To investigate the in vitro effects of suicide gene therepy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer.METHODS: We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method.RESULTS: Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio.CONCLUSION: Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.

  6. Detection of human herpes viruses in patients with chronic and aggressive periodontitis and relationship between viruses and clinical parameters

    OpenAIRE

    Das, Sushma; Krithiga, G Shobha Prakash; Gopalakrishnan, S.

    2012-01-01

    Background and Aims: Recent microbiological researches have revealed the possible role of human cytomegalovirus (HCMV), Epstein barr virus (EBV), and herpes simplex virus (HSV-1 and HSV-2) in the etiopathogenesis of periodontal diseases. The present pilot study has been undertaken to detect the presence of these viruses in chronic periodontitis, aggressive periodontitis, and healthy individuals and to determine the relationship between these viruses and the clinical parameters. Materials and ...

  7. Molecular detection of cytomegalovirus, herpes simplex virus 2, human papillomavirus 16-18 in Turkish pregnants

    Directory of Open Access Journals (Sweden)

    Bedia Dinc

    2010-12-01

    Full Text Available OBJECTIVE: Human cytomegalovirus (CMV is the most common cause of viral intrauterine infections in the world. Herpes simplex virus type 2 (HSV-2 and human papillomavirus (HPV are the main agents of viral sexually transmitted diseases, which cause genital ulcers and genital warts, respectively. HPV infection has been linked to the majority of the anogenital malignancies. The aim of this study was to detect the existence of CMV, HSV-2 and HPV type 16-18 in Turkish pregnants by using sensitive molecular assays. METHODS: One hundred thirty-four women (18-41 years old; mean age ± SD: 27 ± 8 applied to outpatient clinic of Obstetrics and Gynecology, in between 18th - 22nd weeks of their pregnancy and a control group of 99 healthy women (15-39 years old; mean age ± SD: 24 ± 8 were included in the study. Cervical smear samples were used for DNA extraction. CMV, HSV-2 and HPV 16-18 detections were carried out by real time PCR and in house PCR method, respectively. RESULTS: Three patients (3/134; 2.2% were found to be positive for each HPV and HSV-2. Dual infection with HPV and HSV was found in just one patient. HPV 18 was detected in all positive samples. CMV was found to be positive in two patients (2/134; 1.4 %. CONCLUSION: HPV, HSV and CMV must be screened due to high prevalence of these viruses in pregnants by using sensitive molecular methods.

  8. Comprehensive analysis of serum cytokines/chemokines in febrile children with primary human herpes virus-6B infection.

    Science.gov (United States)

    Nagasaka, Miwako; Morioka, Ichiro; Kawabata, Akiko; Yamagishi, Yoshiaki; Iwatani, Sota; Taniguchi-Ikeda, Mariko; Ishida, Akihito; Iijima, Kazumoto; Mori, Yasuko

    2016-09-01

    Cytokines and chemokines induced by primary human herpes virus (HHV)-6B infection may play a critical role in the clinical manifestations of infection. In this study, we analyzed 40 cytokines/chemokines in febrile children with primary HHV-6B infection. Blood samples from 233 febrile and 36 afebrile patients 0-3 years of age were used for this study. In febrile patients, primary HHV-6B infection was determined by detection of HHV-6B DNA without anti-HHV-6 immunoglobulin G in the blood (HHV-6B group). Infection by other pathogens was assumed when HHV-6B DNA was not detected in the blood (non-HHV-6B group). Of the 233 febrile patients, 30 patients (13%) were diagnosed with primary HHV-6B infection. To analyze serum cytokines/chemokines, patients were randomly chosen from the HHV-6B (n = 25) and non-HHV-6B groups (n = 8). Sera from 25 afebrile patients were used as a control. When comparing the levels of 40 cytokines/chemokines between the HHV-6B and control groups, we found that four chemokines (chemokine [C-X-C motif] ligand [CXCL] 11, CXCL10, CXCL16, and chemokine [C-C motif] ligand [CCL] 2) were significantly upregulated in the HHV-6B group compared with those in the control. Of these, only CXCL11 levels were significantly higher in the HHV-6B group than in the non-HHV-6B group. Because the induction of CCL2 was already reported in an early study, we found, for the first time, the induction of three new chemokines, i.e., CXCL11, CXCL10, and CXCL16 in patients with primary HHV-6B infection. Importantly, we demonstrated that serum CXCL11 levels increased specifically in patients with HHV-6B infection. PMID:27346377

  9. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case.

    Science.gov (United States)

    Gomes, Maria Miguel; Antunes, Henedina; Lobo, Ana Luísa; Branca, Fernando; Correia-Pinto, Jorge; Moreira-Pinto, João

    2016-01-01

    A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy's sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy's sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC) was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6) by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160) for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection. PMID:27200203

  10. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case

    Directory of Open Access Journals (Sweden)

    Maria Miguel Gomes

    2016-01-01

    Full Text Available A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy’s sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy’s sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6 by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160 for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection.

  11. Study for Interrelationship Between Human Herpes Simplex Virus Type 2 and Leukemia

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Two different strains of human herpes simplex virus type 2(HHSV-2)and /or murine leukemia virus(MLV)were inoculated into newborn mice.In mice of mixed infection with MLV plus HHSV-2(333) or MLV plus HHSV-2(Wu)incidences of leukemia were respectively 79.16% and 75.00%,and in those inoculated with MLV alone were 41.02% and 44.74% in the experiment for 3 months.The differences of incidences between the two conditions were highly significant(p<0.01).On the contrary,no leukemia was detected in mice that were inoculated with HHSV-2(333) or HHSV-2(Wu)alone and in controls.Leukemia developing time of mice infected with two viruses was earlier than with MLV alone.It is obvious that the induction of murine leukemia resulted from infection of MLV and was independent of HHSV-2(333) and HHSV-2(Wu).Both risen incidences and shortened latencies of murine leukemia were in close relationship with infection of HHSV-2(333) and HHSV-2(Wu).

  12. Vulvar carcinomas: search for sequences homologous to human papillomavirus and herpes simplex virus DNA.

    Science.gov (United States)

    Pilotti, S; Rotola, A; D'Amato, L; Di Luca, D; Shah, K V; Cassai, E; Rilke, F

    1990-07-01

    Ten cases of intraepithelial carcinoma, five with Bowenoid features and five with early invasion, and ten cases of invasive vulvar carcinoma were examined by in situ hybridization and Southern blot analysis using DNA probes for human papillomavirus (HPV) types 6, 11, 16, 18 and 31. HPV DNA was detected in 90% of the intraepithelial cases and in 10% of the invasive cases. All positive cases showed the presence of DNA of HPV type 16. The cases with intraepithelial lesions revealed a strong correlation between the presence of HPV type 16 DNA, cigarette smoking habit, other potential cofactors such as herpes simplex (HSV) DNA sequences and the use of contraceptive drugs, and clinicopathologic features of Bowen's type in situ squamous cell carcinoma. Similar associations were not observed among the cases with invasive disease. While HPV-16 is associated with differentiated Bowenoid type vulvar intraepithelial neoplasia, which appears to be the most common form of early carcinoma of the vulva, the same association was not seen with respect to advanced vulvar invasive squamous cell carcinoma.

  13. Replication of human herpes virus 1 (HHV-1)as a ubiqui-tous virus:A mini review

    Institute of Scientific and Technical Information of China (English)

    Mohammad Derakhshan

    2008-01-01

    Human herpes viruses cause a range of human disorders including cold sores,roseola,genital warts and most importantly,tumours.These viruses cause chronic,latent and recurrent infections.Among them HHV-1 ,an alpha-herpesvirus could become latent after a primary infection,becoming reactivated after later provocation. Epidemically,they are found everywhere and are neurotropic.They also have a rapid and highly regulated rep-lication cycle and usually a broad host and cell range.This article summarizes and focuses on replication strat-egies of the virus.

  14. Suspected chromosomally integrated human herpes virus 6 in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Anna Todisco

    2016-03-01

    Full Text Available Background and aims: We report a case of a 27-year-old male affected by acute myeloid leukaemia MLL-PTD positive. After autologous stem cell transplantation, he was monitored based on cytomegalovirus, Epstein-Barr virus and human herpes virus 6 (HHV-6 DNA quantification in blood. Relapse occurred one year after transplantation; then the patient underwent to allogenic bone marrow transplantation using genotypically HLA-identical donor (sister. HHV-6 DNAemia was positive and persistently elevated, either after autologous either after allogenic transplant suggesting the occurrence of HHV-6 chromosomally integration. The work aim is to prove the occurrence of chromosomally integrated-HHV-6 (ci-HHV-6. Materials and Methods: HHV-6 DNA extraction was performed by automated extractor and DNA was amplified-quantified by Real Time polymerase chain reaction. Species identification was performed by sequencing HHV6-U100 glycoprotein using automated sequencer and sequencing products were analysed using the Blast program. Results: After autologous transplantation HHV6-DNAemia was 5.4 log copies/mL setting to 3.9 log copies/mL for a long period post allogenic transplantation. The patient’s hair follicles were tested for HHV- 6 DNA having positive results. Sequences of both strains of HHV6 extracts from blood and hair follicles resulted species B. HHV6 viral load decreased significantly after Lymphocyte Infusion by ci-HHV6 negative donor (sister, having steady viral load during the following six months of monitoring. One year later, patient is in complete haematological remission. Conclusions: Detection of HHV-6 in hair follicles and HHV-6 DNAemia persistently elevated before allogenic transplant, confirm the occurrence of ci-HHV-6. The observed important decreasing viral load is potentially due to the successful engraftment of ci-HHV-6-negative donor marrow after allogeneic transplant.

  15. Prevalence and clinical consequences of herpes simplex virus type 1 DNA in human cornea tissues

    NARCIS (Netherlands)

    L. Remeijer (Lies); R. Duan (Rui); J.M. van Dun (Jessica); M.A.W. Bettink; A.D.M.E. Osterhaus (Ab); G.M.G.M. Verjans (George)

    2009-01-01

    textabstractBackground. We determined the prevalence and clinical consequences of herpes simplex virus (HSV) type 1 (HSV-1), HSV type 2 (HSV-2), and varicella-zoster virus (VZV) in cornea tissues obtained after penetrating keratoplasty (PKP) was performed. Methods. The excised corneas of 83 patients

  16. Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

    OpenAIRE

    Sirada Pongmuangmul; Supaporn Phumiamorn; Phanchana Sanguansermsri; Nalin Wongkattiya; Ian Hamilton Fraser; Donruedee Sanguansermsri

    2016-01-01

    Objective: To evaluate the monogalactosyl diglyceride (MGDG) and digalactosyl diglyceride (DGDG) from Clinacanthus nutans (C. nutans) for their in vitro antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) by plaque reduction assay. Methods: MGDG and DGDG were extracted with chloroform from C. nutans leaves. MGDG and DGDG were separated from chloroform crude extract using column chromatography, characterized by thin layer chromatography and quantified by high...

  17. Herpes Zoster Ophthalmicus in HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Boateng Wiafe MD MSc

    2003-01-01

    Full Text Available Herpes zoster is a common infection caused by the human herpes virus 3, the same virus that causes chickenpox. It is a member of herpes viridae, the same family as the herpes simplex virus, Epstein- Barr virus, and cytomegalovirus. Herpes zoster ophthalmicus occurs when a latent varicella zoster virus in the trigeminal ganglia involving the ophthalmic division of the nerve is reactivated. Of the three divisions of the fifth cranial nerve, the ophthalmic is involved 20 times more frequently than the other divisions.

  18. Sulfated polysaccharides are potent and selective inhibitors of various enveloped viruses, including herpes simplex virus, cytomegalovirus, vesicular stomatitis virus, and human immunodeficiency virus.

    OpenAIRE

    Baba, M.; Snoeck, R; Pauwels, R; De Clercq, E

    1988-01-01

    Several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, fucoidan, and carrageenans) proved to be potent inhibitors for herpes simplex virus, human cytomegalovirus, vesicular stomatitis virus, Sindbis virus, and human immunodeficiency virus. They were moderately inhibitory to vaccinia virus but not inhibitory to adenovirus, coxsackievirus, poliovirus, parainfluenza virus, and reovirus. These results indicate that, with the exception of parainfluenza virus, enveloped viruses ar...

  19. Human rights against anti-terrorist laws

    OpenAIRE

    Georg Friðgeir Ísaksson

    2009-01-01

    In this essay I will try to answer the question: Are human rights in the UK in jeopardy because of the nation’s increasing anti-terrorist laws? I will focus on the UK, how anti-terrorist laws have been implemented and how they have been used in the UK after the events of the terrorist attacks on 9/11. I chose the UK because of its long tradition of anti-terrorist laws since their dealings with the IRA in the last few decades of the last century. I wanted to take a look at different count...

  20. Herpes simplex virus type 2 or human herpesvirus 8 infection and prostate cancer risk: A meta-analysis.

    Science.gov (United States)

    Ge, Xiaoxiao; Wang, Xiao; Shen, Peng

    2013-05-01

    Prostate cancer is the second most frequently diagnosed type of cancer and the sixth leading cause of cancer mortality among males worldwide. The aim of this study was to investigate the association between the infection by herpes simplex virus type 2 (HSV-2) or human herpesvirus 8 (HHV-8) and the risk of prostate cancer. A systematic literature search was performed using PubMed, Cochrane Library, Web of Science, Scopus, CNKI and CBM. The association of HSV-2 or HHV-8 infection with the risk of prostate cancer was separately assessed. Estimates of the odds ratio (OR) with 95% confidence interval (CI) were pooled by the fixed- or random-effects model. A total of 11 articles with 2,996 cases and 3,875 controls were included in this meta-analysis. HSV-2 infection was associated with increased prostate cancer risk (OR=1.209; 95% CI, 1.003-1.456). Results of the stratified analysis suggested that such an association existed among participants from North and South America (OR=1.226; 95% CI, 1.000-1.503). No significant correlation was observed in the HHV-8 group (OR=1.106; 95% CI, 0.765-1.598). Further investigations and large-sample studies are required to elucidate the possible mechanism underlying viral carcinogenesis and the association between herpes virus infection and the risk of prostate cancer. PMID:24648964

  1. Herpes Simplex

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... Herpes simplex public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  2. Genital Herpes: A Review.

    Science.gov (United States)

    Groves, Mary Jo

    2016-06-01

    Genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide. It is caused by herpes simplex virus (HSV) and characterized by lifelong infection and periodic reactivation. A visible outbreak consists of single or clustered vesicles on the genitalia, perineum, buttocks, upper thighs, or perianal areas that ulcerate before resolving. Symptoms of primary infection may include malaise, fever, or localized adenopathy. Subsequent outbreaks, caused by reactivation of latent virus, are usually milder. Asymptomatic shedding of transmissible virus is common. Although HSV-1 and HSV-2 are indistinguishable visually, they exhibit differences in behavior that may affect management. Patients with HSV-2 have a higher risk of acquiring human immunodeficiency virus (HIV) infection. Polymerase chain reaction assay is the preferred method of confirming HSV infection in patients with active lesions. Treatment of primary and subsequent outbreaks with nucleoside analogues is well tolerated and reduces duration, severity, and frequency of recurrences. In patients with HSV who are HIV-negative, treatment reduces transmission of HSV to uninfected partners. During pregnancy, antiviral prophylaxis with acyclovir is recommended from 36 weeks of gestation until delivery in women with a history of genital herpes. Elective cesarean delivery should be performed in laboring patients with active lesions to reduce the risk of neonatal herpes. PMID:27281837

  3. Cold Sores (Orofacial Herpes)

    Science.gov (United States)

    ... rash and rashes clinical tools newsletter | contact Share | Cold Sores (Orofacial Herpes) Information for adults A A ... face, known as orofacial herpes simplex, herpes labialis, cold sores, or fever blisters, is a common, recurrent ...

  4. Herpes Simplex Virus (HSV)

    Science.gov (United States)

    ... rashes clinical tools newsletter | contact Share | Herpes Simplex Virus (HSV) A parent's guide to condition and treatment ... skin or mouth sores with the herpes simplex virus (HSV) is called primary herpes. This may be ...

  5. Native and recombinant herpes simplex virus type 1 envelope proteins induce human immune T-lymphocyte responses.

    Science.gov (United States)

    Torseth, J W; Cohen, G H; Eisenberg, R J; Berman, P W; Lasky, L A; Cerini, C P; Heilman, C J; Kerwar, S; Merigan, T C

    1987-05-01

    The abilities of whole herpes simplex virus type 1 (HSV-1) antigen (HSV-ag) and purified HSV-1 native and recombinant envelope proteins to stimulate in vitro T-lymphocyte responses were compared in patients with recurrent herpes labialis. Immunochemically purified preparations of native glycoproteins B, C, and D (ngB, ngC, ngD) from cultured HSV-1 as well as expressed recombinant plasmid preparations of gD (rgD-1t, rgD-45K) elicited lymphocyte proliferation (LT) and production of gamma interferon (IFN-gamma) and interleukin-2 (IL-2) only in seropositive individuals. The IFN-gamma induced by rgD-1t correlated with the time to the next herpetic lesion in 19 volunteers followed to recurrence (r = 0.69, P less than 0.008), although the magnitude and frequency of LT and IFN-gamma responses were lower with either recombinant or native purified antigens than with the whole-virus antigen. Combinations of ngB plus ngD or ngB plus ngC plus ngD stimulated more IFN-gamma, equivalent to whole-virus-antigen responses. Recombinant-derived human IL-2 also specifically increased LT and IFN-gamma responses in antigen-driven cultures. ngD stimulated IL-2 and LT responses similar to those of whole-virus antigen and higher than those of ngC. HSV-ag and ngB induced significantly higher titers of total IFN than could be accounted for by IFN-gamma; this was not seen for the other antigens, which induced only IFN-gamma. HSV-ag-driven Leu 2a-, plastic-nonadherent blood cells, unlike whole peripheral blood mononuclear cells, showed evidence of an increase and then a decline in the frequency of HSV-responsive cells after a lesion recurrence. These studies suggest that HSV-1 envelope proteins are capable of stimulating an immune T-helper-cell response which is associated with the prevention of human herpes simplex lesion recurrence. Although the whole virus probably contains additional important antigens, increasing concentrations or combinations of certain purified glycoproteins or the

  6. Human Rights and Cohen's Anti-Statism

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2014-01-01

    G. A. Cohen's critique of standard liberal interpretations of the difference principle has been very influential. According to Cohen, justice is not realized simply because the state's tax policies and other distributive tools maximize the position of the worst off. Rather - possibly in addition ...... in distributive justice that it commits us to an implausible anti-statist view of human rights?......, but not to the exclusion of, certain state policies - justice requires talented people to improve the position of the worst off through their actions in their daily lives. Specifically, it prohibits talented people from insisting on inequality-causing incentives. To this extent, Cohen's view of distributive justice...... is anti-statist. On standard liberal interpretations, human rights are such that, logically, they can be violated only by states, not private individuals. An individual who tortures someone commits a moral wrong but does not violate the victim's human rights. For this reason, the crime is less problematic...

  7. Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

    Directory of Open Access Journals (Sweden)

    Sirada Pongmuangmul

    2016-03-01

    Conclusions: MGDG and DGDG from C. nutans, a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2, probably by inhibiting the late stage of multiplication, suggesting their promising use as anti-HSV agents.

  8. Detection of human herpes virus 6 (HHV 6) in the skin of a patient with primary HHV 6 infection and erythroderma.

    OpenAIRE

    Sumiyoshi, Y.; Akashi, K; Kikuchi, M.

    1994-01-01

    Human herpes virus 6 (HHV 6) has been implicated as the causative agent of exanthema subitum in young children. Recently, we reported two cases of a severe, infectious, mononucleosis-like syndrome resulting from a primary HHV 6 infection in immunocompetent adults. Both of these patients had the skin condition generally referred to as "erythroderma". A skin-biopsy specimen from one of them, a 43 year old man, was examined. Using immunohistochemical staining and in situ hybridisation, lymphocyt...

  9. Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma diagnosed by fluorodeoxyglucose positron emission tomography/computer tomography and laparoscopy

    OpenAIRE

    Wu, Wenzhi; Liu, Jingyun; Hong, Wandong

    2013-01-01

    Human herpes virus 8-unrelated primary effusion lymphoma (PEL)-like lymphoma is a rare type of large B cell lymphoma. This report presents the case of a male with abdominal pain and distension who was found to have massive ascites and enhanced peritoneum, mesenterium and greater omentum on enhanced computer tomography (CT) scan with negative ascitic cytology. The diagnosis of PEL-like lymphoma was established by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and laparoscopic b...

  10. Analysis of Individual Human Trigeminal Ganglia for Latent Herpes Simplex Virus Type 1 and Varicella-Zoster Virus Nucleic Acids Using Real-Time PCR

    OpenAIRE

    Cohrs, Randall J.; Randall, Jessica; Smith, John; Gilden, Donald H.; Dabrowski, Christine; van der Keyl, Harjeet; Tal-Singer, Ruth

    2000-01-01

    Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) establish latent infections in the peripheral nervous system following primary infection. During latency both virus genomes exhibit limited transcription, with the HSV-1 LATs and at least four VZV transcripts consistently detected in latently infected human ganglia. In this study we used real-time PCR quantitation to determine the viral DNA copy number in individual trigeminal ganglia (TG) from 17 subjects. The number of HSV...

  11. Herpes virus production as a marker of repair in ultra-violet irradiated human skin cells of different origin

    International Nuclear Information System (INIS)

    Human skin fibroblast cultures were irradiated with ultraviolet light 0 to 48 hours before infection with herpes simplex virus type 1 (HSV). Different viral yields were obtained according to the origin of the host cells. Cells from normal donors showed a dose-dependent recovery of HSV production during the 36-40 hours following U.V. exposure. The recovery was maximal for a dose at which a plateau level of unscheduled DNA synthesis (UDS) was reached (24Jm-2). In a xeroderma pigmentosum (XP) heterozygote line from a mother of XP children, the level of UDS after irradiation up to 48 Jm-2 was normal whereas the extent of recovery of HSV production capacity was lower than normal. In strains from XP children, with a normal UDS (XP variants), the recovery process was slower and its extent was lower than in normal or XP heterozygote cells. Excision-deficient XP strains from XP children presented little or no recovery, the extent of which was in good agreement with the corresponding level of UDS. Measurement of this recovery seems to be a very sensitive assay for detecting differences in the repair abilities of U.V.-irradiated human skin cells of various origins. (author)

  12. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    Science.gov (United States)

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-03-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.

  13. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  14. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    International Nuclear Information System (INIS)

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells

  15. High seroprevalence of human herpes virus 8 (HHV-8 antibodies among vertically HIV-infected pediatric patients living in Germany

    Directory of Open Access Journals (Sweden)

    C Feiterna-Sperling

    2012-11-01

    Full Text Available Background: Human herpes virus 8 (HHV-8, a gamma herpes virus, is the etiological agent for Kaposi sarcoma (KS. HIV-infected adults with advanced immunodeficiency are at risk. Prevalence data of HHV-8 infection in HIV-infected children living in non-endemic areas are limited. Serologic studies indicate low seroprevalence rates of 3–4% for healthy children living in United States and Germany [1]. Purpose of the study: The aim of the study was to determine the seroprevalence of HHV-8 antibodies among vertically HIV-infected pediatric patients in Germany and to evaluate their association with age, gender, ethnicity, and other demographic factors. Methods: In 2012, a multi-center cross-sectional study was conducted in four University Hospitals in Germany. Stored frozen serum specimens obtained from vertically HIV-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Data on patients' demographic characteristics and medical history were recorded. Results: A total of 214 HIV-infected children and adolescents (105 males, 109 females were included. The median age was 10.2 years (range 1 months–22.6 years. A high proportion of these children (62% was born in Western Europe, whereas 65% (139/214 of their mothers were born in countries outside Western Europe. The majoritiy (91% of the children had been treated with highly active antiretroviral therapy and 55.2% (116/210 had a HIV-viral load<50 copies/mL. The median CD4 cell count was 1000/L (range 3–4400. The overall seroprevalence of HHV-8 antibodies was 23.8% (51/214. Seroprevalence rates did not show significant differences between age or gender. In the group of young children aged 1 month to 35 months, 19.4% (46/31 had HHV-8 antibodies, compared to 25% (25/100 in children aged 36 months to 11 years, and 24.1% (20/83 children 12 years and older. In the study group, seroprevalence rates were significantly lower in children who were born in Western

  16. Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

    Institute of Scientific and Technical Information of China (English)

    高振强; 高志萍; 张涛; 刘喜富

    1997-01-01

    According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious "bystander effect" in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice

  17. Herpes virus production as a marker of repair in ultraviolet irradiated human skin cells of different origin

    International Nuclear Information System (INIS)

    When confluent human skin cultures are ultraviolet (UV)-irradiated before infection with Herpes Simplex type 1 virus (HSV), their capacity to support virus growth is impaired. When the time interval between UV-exposure and infection is increased up to 36 hours, different recoveries of HSV production capacity are observed according to the origin of the host cells. 1) Two normal donors: the cells present a dose dependent recovery which is maximal for a dose (24 J/m2) at which a plateau level of unscheduled DNA synthesis (UDS) is reached. 2) A mother of two Xeroderma Pigmentosum (XP) children: in this line which exhibits a normal level of UDS, the extent of recovery is significantly decreased after exposures 2. 3) An XP child: these cells have a normal level of UDS (XP variant) whereas they present a low extent of recovery as compared with that of the normal subjects. 4) Five XP children: in these excision deficient lines (UDS =3 J/m2. For doses 2, a small recovery with an overshoot of viral production is observed 24 h after UV exposure in the lines (three) which present the highest UDS (10-15%) and not in the two lines which present a very low UDS (1-2%)

  18. HPV and Herpes Zoster Vaccines

    Directory of Open Access Journals (Sweden)

    Özlem Karabudak

    2008-12-01

    Full Text Available Genital warts and Herpes Zoster are relatively frequent encountered diseases in dermatology practice. Cervical cancers are also caused by some spesific types of human papillomaviruses. The purpose of this review is to give some knowledge about the vaccines which were developed for these diseases. (Turkderm 2008; 42: 108-12

  19. Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection.

    Directory of Open Access Journals (Sweden)

    Sarah E Flowerdew

    Full Text Available Following primary infection Herpes simplex virus-1 (HSV-1 establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS, the antibody RT97 against 200 kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82% neurons being the most abundant, and Ret-positive (26.93% the least prevalent. Neurons positive with the antibody RT97 (1253 µm(2 were the largest, and those stained against peripherin (884 µm(2 were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT were detected using in situ hybridization (ISH in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling.

  20. Pregnancy and herpes

    Science.gov (United States)

    ... sick. Symptoms include: Bleeding easily Breathing difficulties Blue appearance ( cyanosis ) Flaring of the nostrils Grunting Rapid breathing ( ... care provider if you have a history of genital herpes. If you have frequent herpes outbreaks, you ...

  1. Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus.

    Science.gov (United States)

    Padma, P; Pramod, N P; Thyagarajan, S P; Khosa, R L

    1998-05-01

    Annona muricata (Annonaceae) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. The minimum inhibitory concentration of ethanolic extract of A. muricata and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

  2. Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Behzad-Behbahani A

    2008-01-01

    Full Text Available This study examined the incidence of human herpes virus-6 (HHV-6 and human cytomegalovirus (HCMV infections that are potentially transmitted to haematopoietic stem cells (HSC transplant recipients via bone marrow (BM or umbilical cord blood (UCB. Bone marrow progenitor cells were collected from 30 allogenic BM donors. UCB HSC were collected from 34 subjects. The extracted DNA was then processed using nested polymerase chain reaction (nPCR technique. HCMV and HHV-6 serological status were determined by enzyme immunoassay (EIA. Nested PCR identified HCMV in 22 (73% of 30 samples of BM progenitor cells but in only eight (23.5% of 34 samples of UBC HSC ( P = 0.001. HHV-6 DNA was detected in 11 (36.6% of 30 BM progenitor cells and in only one (2.9% of 34 UBC cells ( P = 0.002. Both HHV-6 and HCMV infections were determined in nine (26.5% of 34 bone marrow samples. The results indicate that, the risk of HCMV and HHV-6 via BM progenitor cells is higher than transmission by UCB cells ( P= 0.04.

  3. Novel Method Based on Real-Time Cell Analysis for Drug Susceptibility Testing of Herpes Simplex Virus and Human Cytomegalovirus.

    Science.gov (United States)

    Piret, Jocelyne; Goyette, Nathalie; Boivin, Guy

    2016-08-01

    The plaque reduction assay (PRA) is the gold standard phenotypic method to determine herpes simplex virus (HSV) and human cytomegalovirus (HCMV) susceptibilities to antiviral drugs. However, this assay is subjective and labor intensive. Here, we describe a novel antiviral phenotypic method based on real-time cell analysis (RTCA) that measures electronic impedance over time. The effective drug concentrations that reduced by 50% (EC50s) the cytopathic effects induced by HSV-1 and HCMV were evaluated by both methods. The EC50s of acyclovir and foscarnet against a reference wild-type (WT) HSV-1 strain in Vero cells were, respectively, 0.5 μM and 32.6 μM by PRA and 0.8 μM and 93.6 μM by RTCA. The EC50 ratios for acyclovir against several HSV-1 thymidine kinase (TK) mutants were 101.8×, 73.4×, 28.8×, and 35.4× (PRA) and 18.0×, 52.0×, 5.5×, and 87.8× (RTCA) compared to those for the WT. The EC50 ratios for acyclovir and foscarnet against the HSV-1 TK/DNA polymerase mutant were 182.8× and 9.7× (PRA) and >125.0× and 10.8× (RTCA) compared to the WT. The EC50s of ganciclovir and foscarnet against WT HCMV strain AD169 in fibroblasts were, respectively, 1.6 μM and 27.8 μM by PRA and 5.0 μM and 111.4 μM by RTCA. The EC50 ratios of ganciclovir against the HCMV UL97 mutant were 3.8× (PRA) and 8.2× (RTCA) compared to those for the WT. The EC50 ratios of ganciclovir and foscarnet against the HCMV UL97/DNA polymerase mutant were 17.1× and 12.1× (PRA) and 14.7× and 4.6× (RTCA) compared to those for the WT. RTCA allows objective drug susceptibility testing of HSV and HCMV and could permit high-throughput screening of new antivirals. PMID:27252463

  4. Herpes simplex encephalitis (HSE) and the immunocompromised: a clinical and autopsy study of HSE in the settings of cancer and human immunodeficiency virus-type 1 infection.

    Science.gov (United States)

    Schiff, D; Rosenblum, M K

    1998-03-01

    Although herpes simplex encephalitis (HSE) is not regarded as an opportunistic infection, the occurrence of HSE in immunocompromised patients has been documented and the suggestion made that unusual clinical and neuropathologic features characterize the disorder in this population. To further characterize HSE as it affects the immunodeficient, the authors reviewed the clinical and pathological findings in three immunocompromised patients with autopsy-proven HSE. Two patients had cancer (one with lymphoma and another with glioblastoma multiforme), one was known to be human immunodeficiency virus-type 1 (HIV-1)-seropositive and a second was suspected of harboring underlying HIV-1 infection. Two were receiving dexamethasone at onset of HSE. All had fever, mental status changes and new, focal neurological deficits or worsening of established deficits. Cerebrospinal fluid (CSF) pleocytosis was absent or minimal and head computerized tomographic (CT) scans, performed in all cases, were unrevealing. No patient was clinically suspected of having HSE, only one received acyclovir (for concurrent mucocutaneous herpes) and HSE played a major role in all deaths. Autopsy revealed an unusual form of HSE characterized by a noninflammatory, pseudoischemic histological presentation and the unexpected persistence of viral antigens in abundance despite survival beyond the clinical stage during which inflammatory responses usually peak and productive brain infection wanes. The incidence of HSE in the immunocompromised may be underestimated. Preexistent neurological disease, a noninflammatory CSF profile and negative CT scan may confound the diagnosis in this population, a typical clinical presentation notwithstanding. Increased clinical suspicion, the use of magnetic resonance imaging and polymerase chain reaction analysis of CSF for herpes simplex virus nucleic acid sequences may permit more rapid diagnosis and treatment. The absence of inflammatory infiltrates in some fatal cases of

  5. Characterization Analysis of Human Anti-Ferritin Autoantibodies

    OpenAIRE

    Shusaku Higashi; Kosei Nagasawa; Yasunaga Yoshikawa; Kiyotaka Watanabe; Koichi Orino

    2014-01-01

    Anti-ferritin autoantibodies are found in many animals. Human ferritin-binding proteins (FBPs) were partially purified from human serum by ion-exchange chromatography and immobilized metal affinity chromatography with Zn2+. Crude FBPs were immunocoprecipitated with canine liver ferritin followed by the addition of anti-ferritin antibodies. Immunoglobulins in the immunocoprecipitate were detected with antibodies specific for human IgG, IgM or IgA heavy chains, and immunoglobulins IgG, IgM and ...

  6. The Changing Epidemiology of Herpes Simplex Virus Type 1 Infection: The Associated Effects on the Incidence of Ocular Herpes

    Directory of Open Access Journals (Sweden)

    Abedi Kiasari, B.

    2016-07-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 with a worldwide distribution has been reported in all human populations, resulting in a clinical spectrum of infections. Although HSV type 2 (HSV-2 is known as the most common cause of genital herpes, an increasing number of cases with genital herpes are caused by HSV-1. The present study aimed to discuss the changes in the epidemiology of HSV-1 infection including the decline in the general incidence of HSV-1 infection in childhood and the increased rate of genital herpes, caused by HSV-1. Moreover, changes in the epidemiology of ocular herpes, i.e., the reduced rate of primary ocular herpes in children and increased incidence of ocular HSV infection in adults, were discussed.

  7. [QUANTITATIVE DNA EVALUATION OF THE HIGH CARCINOGENIC RISK OF HUMAN PAPILLOMA VIRUSES AND HUMAN HERPES VIRUSES IN MALES WITH FERTILITY DISORDERS].

    Science.gov (United States)

    Evdokimov, V V; Naumenko, V A; Tulenev, Yu A; Kurilo, L F; Kovalyk, V P; Sorokina, T M; Lebedeva, A L; Gomberg, M A; Kushch, A A

    2016-01-01

    Infertility is an actual medical and social problem. In 50% of couples it is associated with the male factor and in more than 50% of cases the etiology of the infertility remains insufficiently understood. The goal of this work was to study the prevalence and to perform quantitative analysis of the human herpes viruses (HHV) and high carcinogenic risk papilloma viruses (HR HPV) in males with infertility, as well as to assess the impact of these infections on sperm parameters. Ejaculate samples obtained from 196 males fall into 3 groups. Group 1 included men with the infertility of unknown etiology (n = 112); group 2, patients who had female partners with the history of spontaneous abortion (n = 63); group 3 (control), healthy men (n = 21). HHV and HR HPV DNA in the ejaculates were detected in a total of 42/196 (21.4%) males: in 31 and 11 patients in groups 1 and 2, respectively (p > 0.05) and in none of healthy males. HHV were detected in 24/42; HR HPV, in 18/42 males (p > 0.05) without significant difference between the groups. Among HR HPV genotypes of the clade A9 in ejaculate were more frequent (14/18, p = 0.04). Comparative analysis of the sperm parameters showed that in the ejaculates of the infected patients sperm motility as well as the number of morphologically normal cells were significantly reduced compared with the healthy men. The quantification of the viral DNA revealed that in 31% of the male ejaculates the viral load was high: > 3 Ig10/100000 cells. Conclusion. The detection of HHV and HR HPV in the ejaculate is associated with male infertility. Quantification of the viral DNA in the ejaculate is a useful indicator for monitoring viral infections in infertility and for decision to start therapy. PMID:27451497

  8. Individuals with inherited chromosomally integrated human herpes virus 6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity.

    Science.gov (United States)

    Strenger, V; Kayser, S; Witte, K-E; Lassner, D; Schwinger, W; Jahn, G; Urban, C; Feuchtinger, T

    2016-02-01

    To evaluate the human herpes virus 6 (HHV-6) -specific immune response in individuals with chromosomally integrated HHV-6 (ciHHV-6), we measured HHV-6-antigen-specific cytokine responses (interferon-γ, interleukin-2, tumour necrosis factor-α) in T cells by flow cytometry in 12 and 16 individuals with and without ciHHV-6, respectively. All individuals with ciHHV-6 showed HHV-6-specific T cells with higher frequencies of HHV-6-specific CD8(+) cells (0.03-14.93, median 2.15% of CD8(+) cells) compared with non-ciHHV-6 (0.0-10.67, median 0.36%, p 0.026). The observed increased HHV-6-specific functionally active responses in individuals with ciHHV-6 clearly disprove speculations on immune tolerance in ciHHV-6 and indicate clinical and immunological implications of ciHHV-6. PMID:26482270

  9. The sexuality assemblage: Desire, affect, anti-humanism

    OpenAIRE

    Fox, NJ; Alldred, P

    2013-01-01

    Two theoretical moves are required to resist the ‘humanist enticements’ associated with sexuality. Post-structuralism supplies the first, showing how the social produces culturally-specific sexual knowledgeabilities. A second anti-humanist move is then needed to overturn anthropocentric privileging of the human body and subject as the locus of sexuality. In this paper we establish a language and landscape for a Deleuze inspired anti-humanist sociology of sexuality that shifts the location of ...

  10. Serum herpes simplex antibodies

    Science.gov (United States)

    ... different samples. Talk to your doctor about the meaning of your specific test results. What Abnormal Results ... partner know that you have herpes before having sex. Allow him or her to decide what to ...

  11. Genital Herpes (For Parents)

    Science.gov (United States)

    ... to prevent a herpes infection altogether. Anyone having sex (oral, anal, or vaginal) should take precautions against STDs ... the risk of STDs. Latex condoms provide greater protection than natural-membrane condoms. The female condom, made ...

  12. Preparation of humanized ovarian carcinoma anti-idiotypic minibody.

    Science.gov (United States)

    Chang, Xiaohong; Cui, Heng; Feng, Jie; Li, Yi; Liu, Bei; Cao, Shanjin; Cheng, Yexia; Qian, Henian

    2003-04-01

    Murine anti-idiotypic monoclonal antibody (MAb) 6B11 mimicking the tumor-associated antigen OC166-9 is used as a vaccine for the induction of an anti-tumoral immunity in experiments of in vitro and in vivo animal model with ovarian carcinoma. In this article, we have humanized 6B11 anti-idiotypic minibody using overlap polymerase chain reaction (PCR) and DNA recombinant technique, prokaryotic expression vector was produced by genetic fusion of 6B11V(L)-V(H) to human IgG1 hinge and CH3 region. Transformed E. coli BL21(DE3) were propagated and induced by isopropyl-beta D-thiogalactopyranoside (IPTG). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein band with molecular weight of 50kD appeared as the expected size after transformation. Molecular weight of 100 kDa may be examined by electrophoresis in nondenaturing systems. The fusion protein was analyzed with enzyme-linked immunosorbant assay (ELISA), inhibition ELISA tests and Western blot, respectively. The humanized anti-idiotype minibody showed capacity of bivalent binding to ovarian cancer MAb COC166-9 and goat anti-human immunoglobulin IgG1. It is useful reagents for clinical use. PMID:12831536

  13. Herpes zoster infection

    OpenAIRE

    Mohit Bansal; Sunint Singh; Saryu Arora; Sanjeev Laller; Manpeet Walia

    2012-01-01

    Herpes zoster (HZ) or ′shingles′ results from reactivation of the varicella-zoster virus (VZV). Developmental anomalies, osteonecrosis of jaw bones, and facial scarring are the other complications associated with it. Primary VZV infections in sero-negative individuals are known as varicella or chicken pox. Secondary or reactivated disease is known as shingles or herpes zoster. Early diagnosis and prompt treatment of the disease in the prodromal phase by the use of antiviral agents should be t...

  14. Herpes simplex virus type 2 virion host shutoff protein suppresses innate dsRNA antiviral pathways in human vaginal epithelial cells.

    Science.gov (United States)

    Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2011-09-01

    Viruses that establish persistent infections have evolved numerous strategies to evade host innate antiviral responses. We functionally assessed the role of herpes simplex virus type 2 (HSV-2) virion host shutoff (vhs) protein on innate immune sensing pathways in human vaginal epithelial cells (VK2 ECs). Infection of cells with wild-type (WT) HSV-2 significantly decreased expression of innate immune sensors of viral infection, Toll-like receptor (TLR)2, TLR3, retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda-5), relative to cells infected with a mutant that lacks vhs (vhsB) or mock-infected cells. Transfection with HSV-2 vhs similarly decreased expression of TLR2, TLR3, RIG-I and Mda-5, which was also confirmed in human embryonic kidney (HEK) 293 cells. vhsB infection of VK2 cells caused robust increases in the active form of interferon regulatory factor (IRF)3 and its translocation to the nucleus compared with the WT. Additionally, IRF3 activation by Sendai virus and polyinosinic : polycytidylic acid-induced stimulation of beta interferon (IFN-β) was significantly inhibited in vhs-transfected cells. Overall, our findings provide the first evidence that HSV-2 vhs plays roles in selectively inhibiting TLR3 and RIG-I/Mda-5, as well as TLR2-mediated antiviral pathways for sensing dsRNA and effectively suppresses IFN-β antiviral responses in human vaginal ECs.

  15. Genital herpes - self-care

    Science.gov (United States)

    Herpes - genital -self-care; Herpes simplex - genital - self-care; Herpesvirus 2 - self-care; HSV-2 - self-care ... yourself healthy can also minimize the risk of future outbreaks. Things you can do include: Get plenty ...

  16. Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

    International Nuclear Information System (INIS)

    Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccinees studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccinees proliferated following stimulation with gD-2, whereas stimulation with Gd-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine

  17. [{sup 11}C]FMAU and [{sup 18}F]FHPG as PET tracers for herpes simplex virus thymidine kinase enzyme activity and human cytomegalovirus infections

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Erik F.J. de E-mail: e.f.j.de.vries@pet.azg.nl; Waarde, Aren van; Harmsen, Marco C.; Mulder, Nanno H.; Vaalburg, Willem; Hospers, Geke A.P

    2000-02-01

    [{sup 11}C]-2'-Fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 11}C]FMAU) and [{sup 18}F]-9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG), radiolabeled representatives of two classes of antiviral agents, were evaluated as tracers for measuring herpes simplex virus thymidine kinase (HSV-tk) enzyme activity after gene transfer and as tracers for localization of active human cytomegalovirus (HCMV) infections. In vitro accumulation experiments revealed that both [{sup 11}C]FMAU and [{sup 18}F]FHPG accumulated significantly more in HSV-tk expressing cells than they did in control cells. [{sup 18}F]FHPG uptake in HSV-tk expressing cells, however, was found to depend strongly on the cell line used, which might be due to cell type dependent membrane transport or cell type dependent substrate specific susceptibility of the enzyme. In vitro, both tracers exhibited a good selectivity for accumulation in HCMV-infected human umbilical vein endothelial cells over uninfected cells. In contrast to [{sup 18}F]FHPG, [{sup 11}C]FMAU uptake in control cells was relatively high due to phosphorylation of the tracer by host kinases. Therefore, [{sup 18}F]FHPG appears to be the more selective tracer not only to predict HSV-tk gene therapy outcome, but also to localize active HCMV infections with PET.

  18. Herpes simplex virus (HSV)-specific proliferative and cytotoxic T-cell responses in humans immunized with an HSF type 2 glycoprotein subunit vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Zarling, J.M.; Moran, P.A.; Brewer, L.; Ashley, R.; Corey, L.

    1988-12-01

    Studies were undertaken to determine whether immunization of humans with a herpes simplex virus type 2 (HSV-2) glycoprotein-subunit vaccine would result in the priming of both HSV-specific proliferating cells and cytotoxic T cells. Peripheral blood lymphocytes (PBL) from all eight vaccinees studied responded by proliferating after stimulation with HSV-2, HSV-1, and glycoprotein gB-1. The PBL of five of these eight vaccinees proliferated following stimulation with gD-2, whereas stimulation with Gd-1 resulted in relatively low or no proliferative responses. T-cell clones were generated from HSV-2-stimulated PBL of three vaccinees who demonstrated strong proliferative responses to HSV-1 and HSV-2. Of 12 clones studied in lymphoproliferative assays, 9 were found to be cross-reactive for HSV-1 and HSV-2. Of the approximately 90 T-cell clones isolated, 14 demonstrated HSV-specific cytotoxic activity. Radioimmunoprecipitation-polyacrylamide gel electrophoresis analyses confirmed that the vaccinees had antibodies only to HSV glycoproteins, not to proteins which are absent in the subunit vaccine, indicating that these vaccinees had not become infected with HSV. Immunization of humans with an HSV-2 glycoprotein-subunit vaccine thus results in the priming of T cells that proliferate in response to stimulation with HSV and its glycoproteins and T cells that have cytotoxic activity against HSV-infected cells. Such HSV-specific memory T cells were detected as late as 2 years following the last boost with the subunit vaccine.

  19. Thymidine kinase deficient human cells have increased UV sensitivity in their capacity to support herpes simplex virus but normal UV sensitivity for colony formation

    International Nuclear Information System (INIS)

    A thymidine kinase deficient (tk-) and two thymidine kinase proficient (tk+) human cell lines were compared for UV sensitivity using colony-forming ability as well as their capacity to support the plaque formation of herpes simplex type 1 (HSV-1).The tk- line (143 cells) was a derivative of one of the tk+ lines (R970-5), whereas the other tk+ line (AC4 cells) was a derivative of the 143 cells obtained by transfection with purified sheared HSV-2 DNA encoding the viral tk gene. 143, R970-5 and AC4 cells showed a similar UV sensitivity for colony-forming ability. In contrast, the capacity to support HSV-1 plaque formation immediately (within 1 h) afte UV-irradiation was reduced to a greater extent in the 143 cells compared to the R970-5 and AC4 cells. Capacity curves for plaque formation of the HSV-1: KOS wild-type (tk+) strain were similar to those for the HSV-1: PTK3B mutant (tk-) strain were similar to those for the HSV-1: PTK3B mutant (tk-) strain in the 3 cell strains, indicating that the viral tk gene does not influence the ability of HSV-1 to form plaques in UV-irradiated compared to unirradiated human cells. Cellular capacity for HSV-1 plaque formation was found to recover in both tk- and tk+ cells for cultures infected 24 h after UV-irradiation. These results suggest that repair of UV-damaged DNA takes place to a similar extent in both tk- and tk+ human cells, but the kinetics of repair are initially slower in tk-compared to tk+ human cells. (author). 33 refs.; 3 figs.; 1 tab

  20. Antiviral Activity of Trappin-2 and Elafin In Vitro and In Vivo against Genital Herpes

    OpenAIRE

    Drannik, Anna G.; Nag, Kakon; Sallenave, Jean-Michel; Rosenthal, Kenneth L

    2013-01-01

    Serine protease inhibitor elafin (E) and its precursor, trappin-2 (Tr), have been associated with mucosal resistance to HIV-1 infection. We recently showed that Tr/E are among principal anti-HIV-1 molecules in cervicovaginal lavage (CVL) fluid, that E is ∼130 times more potent than Tr against HIV-1, and that Tr/E inhibited HIV-1 attachment and transcytosis across human genital epithelial cells (ECs). Since herpes simplex virus 2 (HSV-2) is a major sexually transmitted infection and risk facto...

  1. Herpes zoster infection

    Directory of Open Access Journals (Sweden)

    Mohit Bansal

    2012-01-01

    Full Text Available Herpes zoster (HZ or ′shingles′ results from reactivation of the varicella-zoster virus (VZV. Developmental anomalies, osteonecrosis of jaw bones, and facial scarring are the other complications associated with it. Primary VZV infections in sero-negative individuals are known as varicella or chicken pox. Secondary or reactivated disease is known as shingles or herpes zoster. Early diagnosis and prompt treatment of the disease in the prodromal phase by the use of antiviral agents should be the mainstay of its management. This paper presents a case report of such an infection and its management.

  2. Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus.

    Science.gov (United States)

    Ensign, Laura M; Lai, Samuel K; Wang, Ying-Ying; Yang, Ming; Mert, Olcay; Hanes, Justin; Cone, Richard

    2014-12-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large polyethylene glycol (PEG)-coated, nonmucoadhesive nanoparticles (PS-PEG) did not change in F127-pretreated CVM, implying that F127 did not significantly alter the native pore structure of CVM. Additionally, herpes simplex virus type 1 (HSV-1) remains adherent in F127-pretreated CVM, indicating that the presence of F127 did not reduce adhesive interactions between CVM and the virions. In contrast to treatment with a surfactant that has been approved for vaginal use as a spermicide (nonoxynol-9 or N9), there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for 1 week. Pluronic F127 pretreatment holds potential as a method to safely improve the distribution, retention, and efficacy of nanoparticle formulations without compromising CVM barrier properties to pathogens. PMID:25347518

  3. Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis

    Directory of Open Access Journals (Sweden)

    Staffan Görander

    2014-11-01

    Full Text Available We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2 of herpes simplex virus 2 (HSV-2 in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1 and IgG2 antibodies were detected and re-stimulated splenic CD4+ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC and complement-mediated cytolysis (ACMC activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.

  4. A human osteosarcoma cell line expressing herpes simplex type-1 thymidine kinase: studies with radiolabeled (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine

    International Nuclear Information System (INIS)

    Introduction: (E)-5-(2-Iodovinyl)-2'-fluoro-2'-deoxyuridine (IVFRU) is a pyrimidine nucleoside analogue that accumulates selectively in murine cells expressing herpes simplex type-1 thymidine kinase (HSV-1 TK). The uptake of [125I]IVFRU in human 143B osteosarcoma cells transduced with a retroviral vector bearing the HSV-1 TK gene (143B-LTK cells) is now reported. Methods: HSV-1 TK gene expression in 143B-LTK cells was confirmed by Western blotting and reverse transcriptase (RT)-PCR. Cell and subcellular uptake of [125I]IVFRU was determined in cell culture, and whole body biodistribution after intravenous injection of [125I]IVFRU was determined using nude mice bearing implanted 143B or 143B-LTK tumors. Results: Although IVFRU was less toxic to the human cell line expressing HSV-1 TK (143B-LTK) than ganciclovir, both IVFRU and ganciclovir were not toxic to the cell line not expressing HSV-1 TK (143B). When cells were exposed to [125I]IVFRU in vitro, only the 143B-LTK cells accumulated radioactivity. The acid-soluble fraction from 143B-LTK cell lysates contained 8-fold greater activity than the acid-insoluble fraction after an 8-h exposure to [125I]IVFRU. Biodistribution of [125I]IVFRU in nude mice bearing subcutaneous 143B and 143B-LTK tumors revealed widespread distribution of the nucleoside in vivo but with specific localization in 143B-LTK tumors. Conclusion: The underlying biochemical process of metabolic entrapment of IVFRU in human osteosarcoma cells expressing HSV-1 TK is responsible for selective localization in these cells. The differences in subcellular distribution into the nucleic acid fraction, and in cytotoxicity, reflect the importance of cell type and lineage as determinants of the performance of gene imaging radiopharmaceuticals

  5. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

    Directory of Open Access Journals (Sweden)

    Mark A Little

    Full Text Available Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3 antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis. Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17% more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  6. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

    LENUS (Irish Health Repository)

    Little, Mark A

    2012-01-01

    Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener\\'s granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻\\/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17%) more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  7. Relationships among cell survival, O6-alkylguanine-DNA alkyltransferase activity, and reactivation of methylated adenovirus 5 and herpes simplex virus type 1 in human melanoma cell lines

    International Nuclear Information System (INIS)

    O6-Alkylguanine-DNA alkyltransferase (ATase) activity and host cell reactivation (HCR) of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC)-methylated viruses were compared in human melanoma cell lines that were sensitive or resistant to killing by the antitumor DNA-methylating agent MTIC. Enhanced HCR of adenovirus 5 (defined as the Mer+ phenotype) generally showed a semiquantitative correlation with the natural or induced resistance of the host cells to the toxic effects of MTIC and to the level of ATase activity. However, one MTIC-resistant cell line was found (MM170) which had a low level of ATase and intermediate HCR of adenovirus. The HCR of herpes simplex virus type 1 (HSV-1) was enhanced in the Mer+ cells that had natural resistance to MTIC compared with Mer- cells. On the other hand, HCR of HSV-1 in Mer+ cells with induced resistance to MTIC was similar to that in Mer- cells. Neither adenovirus 5 nor HSV-1 infection induced ATase activity in Mer- cells. This indicates that resistance to the toxic effects of methylating agents is not invariably associated with high levels of ATase activity in human melanoma cells. Furthermore, while induction of the Mer+ phenotype from Mer- cells was usually accompanied by the recovery of ATase activity, induced Mer+ cells had less proficient repair than natural Mer+ cells, as judged quantitatively by slightly lower cellular resistance and qualitatively by deficient HCR response for HSV-1. These results suggest that the Mer- and induced Mer+ cells lack an ATase-independent DNA repair mechanism. No differences in MTIC-induced DNA repair synthesis or strand breaks were found between the Mer-, natural Mer+, and induced Mer+ phenotypes. However, UV-induced DNA repair synthesis was higher in the natural Mer+ than in the Mer- or induced Mer+ cells, both of which had increased cellular sensitivity to the antimetabolites methotrexate and hydroxyurea

  8. Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human HepatocelLular Carcinoma in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    LI Bao-jin; ZHANG Chao; YI Yuan-xue; HAO Ying; LIU Xiao-ping; OU Qing-jia

    2007-01-01

    Objective: To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) in combination of ganciclovir (GCV) against human hepatocellular carcinoma in nude mice. Methods: HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups (n=8 each group): Ganciclovir group (Ⅰ), Ad group (Ⅱ), AdCMV-tk/GCV group (under the driving of CMV promoter) (Ⅲ) and AdKDR-tk/GCV group (Ⅳ). Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/(kg·d), ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results: Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and Ⅳ (P<0.05). The mean MVDs in group Ⅰ, Ⅱ, Ⅲand Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 (microvessels/mm2), respectively. Significant differences were found between group Ⅲ and Ⅱ (P<0.05), Ⅳ and Ⅱ (P<0.01), and Ⅳ and Ⅲ (P<0.01). Conclusion: Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC.

  9. The Possibility of Using Serum Concentrations of the Tumor Necrosis Factor-Alpha as a Biomarker in Mesial Temporal Lobe Epilepsy Associated With the Human Herpes Virus Neuroinfections

    Directory of Open Access Journals (Sweden)

    Yaroslav Ya. Nedopako

    2012-03-01

    Full Text Available In this study, mesial temporal lobe epilepsy (MTLE is shown to be associated with human herpes virus (HHV neuroinfections. We also demonstrate that the epileptic process is associated with an inflammatory reaction, and that the proinflammatory cytokine, the tumor necrosis factor-alpha (TNF-α is able to potentiate the reproduction of the herpesviruses. The study group (SG included 43 patients between 16 and 60 years with MTLE and HHV neuroinfections, diagnosed according to the PCR of the cerebrospinal fluid (CSF, serum or abnormal serum/CSF IgG ratio. The control group (CG included 20 patients of similar age with MTLE, but without the HHV neuroinfections. The concentration of TNF-α in the serum was determined by enzyme-linked immunosorbent assay ("VektorBEST" RF; N=0-50 pg/ml. Patients of the SG had high concentrations of TNF-α in serum (288±44.7 pg/ml, that were significantly higher than in the CG (p<0.05;Z

  10. Apolipoprotein 4 may increase viral load and seizure frequency in mesial temporal lobe epilepsy patients with positive human herpes virus 6B.

    Science.gov (United States)

    Huang, Cheng; Yan, Bo; Lei, Ding; Si, Yang; Li, He; Chen, Ming-Wan; Li, Li; Chen, Fei; Zhou, Qiao; Zhou, Dong; Li, Jin-Mei

    2015-04-23

    This study investigated whether apolipoprotein 4 (ApoE4) was associated with the presence of human herpes virus (HHV)-6B in mesial temporal lobe epilepsy (MTLE). Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) was used to determine ApoE polymorphism in 46 patients with MTLE and 19 controls. Nested PCR and real-time PCR were applied to determine HHV-6B DNA and immunohistochemistry (IHC) for HHV-6B protein. Viral DNA load was significantly increased in MTLE patients with HHV-6B(+)/ApoE4 compared with those with HHV-6B(+)/non-ApoE4 (p=0.031). Semi-quantitative analysis of IHC showed significantly increased number of positive cells for HHV-6B proteins G116/64/54, P98 and U94 in patients with HHV-6B(+)/ApoE4 than HHV-6B(+)/non-ApoE4 (p=0.009, 0.035 and 0.009, respectively). Patients with HHV-6B(+)/ApoE4 showed higher seizure frequency than those with HHV-6B(+)/non-ApoE4 (p=0.005). There was no significant difference of ApoE alleles between MTLE with and without HHV-6B (p=0.115). ApoE4 was not associated with initial infection of HHV-6B in MTLE. However, ApoE4 may facilitate HHV-6B reactivation, DNA replication, virus protein expression and increase seizure frequency in MTLE. Further investigations are needed to understand the biomolecular mechanism underlying interaction between ApoE and HHV-6B.

  11. Targeting of herpes simplex virus 1 thymidine kinase gene sequences into the OCT4 locus of human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Wu Ou

    Full Text Available The in vitro differentiation of human induced pluripotent stem cells (hiPSC to generate specific types of cells is inefficient, and the remaining undifferentiated cells may form teratomas. This raises safety concerns for clinical applications of hiPSC-derived cellular products. To improve the safety of hiPSC, we attempted to site-specifically insert a herpes simplex virus 1 thymidine kinase (HSV1-TK suicide gene at the endogenous OCT4 (POU5F1 locus of hiPSC. Since the endogenous OCT4 promoter is active in undifferentiated cells only, we speculated that the HSV1-TK suicide gene will be transcribed in undifferentiated cells only and that the remaining undifferentiated cells can be depleted by treating them with the prodrug ganciclovir (GCV prior to transplantation. To insert the HSV1-TK gene at the OCT4 locus, we cotransfected hiPSC with a pair of plasmids encoding an OCT4-specific zinc finger nuclease (ZFN and a donor plasmid harboring a promoter-less transgene cassette consisting of HSV1-TK and puromycin resistance gene sequences, flanked by OCT4 gene sequences. Puromycin resistant clones were established and characterized regarding their sensitivity to GCV and the site of integration of the HSV1-TK/puromycin resistance gene cassette. Of the nine puromycin-resistant iPSC clones analyzed, three contained the HSV1-TK transgene at the OCT4 locus, but they were not sensitive to GCV. The other six clones were GCV-sensitive, but the TK gene was located at off-target sites. These TK-expressing hiPSC clones remained GCV sensitive for up to 90 days, indicating that TK transgene expression was stable. Possible reasons for our failed attempt to selectively target the OCT4 locus are discussed.

  12. Monoclonal antibodies to Herpes Simplex Virus Type 2

    International Nuclear Information System (INIS)

    In this thesis the production and characterisation of monoclonal antibodies to Herpes Simplex Virus Type 2 is described. The development of a suitable radioimmunoassay for the detection of anti-HSV-2 antibodies, and the selection of an optimal immunisation schedule, is given. Three assay systems are described and their reliability and sensitivity compared. (Auth.)

  13. Herpes simplex type 2 pneumonia

    OpenAIRE

    Edenilson Eduardo Calore

    2002-01-01

    Extensive reviews of pulmonary infections in AIDS have reported few herpetic infections. Generally these infections are due to Herpes simplex type 1. Pneumonia due to herpes type 2 is extremely rare. We describe a 40 year-old HIV positive woman who complained of fever, cough and dyspnea for seven years. She had signs of heart failure and the appearance of her genital vesicles was highly suggestive of genital herpes. Echocardiography showed marked pulmonary hypertension, right ventricular hype...

  14. Herpes Simplex Virus Type 1 (HSV-1)-Induced Apoptosis in Human Dendritic Cells as a Result of Downregulation of Cellular FLICE-Inhibitory Protein and Reduced Expression of HSV-1 Antiapoptotic Latency-Associated Transcript Sequences▿

    OpenAIRE

    Kather, Angela; Raftery, Martin J.; Devi-Rao, Gayathri; Lippmann, Juliane; Giese, Thomas; Sandri-Goldin, Rozanne M.; Schönrich, Günther

    2009-01-01

    Herpes simplex virus type 1 (HSV-1) is one of the most frequent and successful human pathogens. It targets immature dendritic cells (iDCs) to interfere with the antiviral immune response. The mechanisms underlying apoptosis of HSV-1-infected iDCs are not fully understood. Previously, we have shown that HSV-1-induced apoptosis of iDCs is associated with downregulation of the cellular FLICE-inhibitory protein (c-FLIP), a potent inhibitor of caspase-8-mediated apoptosis. In this study, we prove ...

  15. [VIRAL INFECTIONS: HUMAN PAPILLOMAVIRUS AND GENITAL HERPES TYPE 1 AND TYPE 2 AS A CAUSE OF CHRONIC RECURRENT CYSTITIS WITH SEVERE DYSURIA IN WOMEN WITH URETHRAL HYPERMOBILITY AND HYPOSPADIAS].

    Science.gov (United States)

    Derevjanko, T I; Ryzhkov, V V

    2015-01-01

    Female hypospadias presenting as a misplaced urethral opening is a common cause of chronic recurrent cystitis. Cystitis occurs when urogenital infection and anaerobic bacteria enter the urethra and bladder from the vagina. The authors argue that chronic infections of the lower urinary tract in women with hypospadias should be treated surgically by meatal transposition. They present a study confirming the role of the antiviral drug Panavir in prevention of inflammatory complications in the postoperative period in patients with a history of viral infection (human papillomavirus and herpes). PMID:26665761

  16. An Unusual Psychiatric Emergency: Herpes Simplex Encephalitis

    Directory of Open Access Journals (Sweden)

    H. Doyle

    1994-01-01

    Full Text Available A case of fatal herpes simplex virus (HSV encephalitis, presenting as a psychiatric emergency, is reported. The possibility of HSV encephalitis presenting mainly or solely with psychiatric symptoms is highlighted. HSV can cause a severe form of encephalitis which may present with mainly psychiatric symptoms in some cases. Early treatment with anti-viral agents can reduce mortality and morbidity, but accurate early diagnosis may be very difficult. HSV encephalopathy may mimic psychiatric illness and has been likened to syphilis as the great imitator. The case presented here should serve to raise awareness of the psychiatric features and the need to consider this diagnosis in patients with atypical behavioural disturbance.

  17. [Ocular hypertension in herpes simplex keratouveitis].

    Science.gov (United States)

    Burcea, M; Avram, Corina-Ioana; Stamate, Alina-Cristina; Malciolu, R; Oprea, S; Zemba, M

    2014-01-01

    The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

  18. Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells.

    Science.gov (United States)

    Medda, Rituparna; Lyros, Orestis; Schmidt, Jamie L; Jovanovic, Nebojsa; Nie, Linghui; Link, Benjamin J; Otterson, Mary F; Stoner, Gary D; Shaker, Reza; Rafiee, Parvaneh

    2015-01-01

    Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-α/IL-1β with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial cell-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-α/IL-1β-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1β activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.

  19. Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice

    NARCIS (Netherlands)

    Kuipers, M.E; Swart, P.J; Schutten, M; Smit, C; Proost, Hans; Osterhaus, A.DME; Meijer, D.K F

    1997-01-01

    Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour

  20. Outbreaks of human-herpes virus 6 (HHV-6 infection in day-care centers in Belém, Pará, Brazil

    Directory of Open Access Journals (Sweden)

    FREITAS Ronaldo B.

    2000-01-01

    Full Text Available A total of 730 children aged less than 7 years, attending 8 day-care centers (DCCs in Belém, Brazil were followed-up from January to December 1997 to investigate the occurrence of human-herpes virus 6 (HHV-6 infection in these institutional settings. Between October and December 1997 there have been outbreaks of a febrile- and -exanthematous disease, affecting at least 15-20% of children in each of the DCCs. Both serum- and- plasma samples were obtained from 401 (55% of the 730 participating children for the detection of HHV-6 antibodies by enzyme-linked immunosorbent assay (ELISA, and viral DNA amplification through the nested-PCR. Recent HHV-6 infection was diagnosed in 63.8% (256/401 of them, as defined by the presence of both IgM and IgG-specific antibodies (IgM+/IgG+; of these, 114 (44.5% were symptomatic and 142 (55.5% had no symptoms (p = 0.03. A subgroup of 123 (30.7% children were found to be IgM-/IgG+, whereas the remaining 22 (5.5% children had neither IgM nor IgG HHV-6- antibodies (IgM-/IgG-. Of the 118 children reacting strongly IgM-positive ( > or = 30 PANBIO units, 26 (22.0% were found to harbour the HHV-6 DNA, as demonstrated by nested-PCR. Taken the ELISA-IgM- and- nested PCR-positive results together, HHV-6 infection was shown to have occurred in 5 of the 8 DCCs under follow-up. Serological evidence of recent infections by Epstein-Barr virus (EBV and parvovirus B19 were identified in 2.0% (8/401 and 1.5% (6/401 of the children, respectively. Our data provide strong evidence that HHV-6 is a common cause of outbreaks of febrile/exanthematous diseases among children attending DCCs in the Belém area.

  1. The virion host shut-off (vhs protein blocks a TLR-independent pathway of herpes simplex virus type 1 recognition in human and mouse dendritic cells.

    Directory of Open Access Journals (Sweden)

    Christopher R Cotter

    Full Text Available Molecular pathways underlying the activation of dendritic cells (DCs in response to Herpes Simplex Virus type 1 (HSV-1 are poorly understood. Removal of the HSV virion host shut-off (vhs protein relieves a block to DC activation observed during wild-type infection. In this study, we utilized a potent DC stimulatory HSV-1 recombinant virus lacking vhs as a tool to investigate the mechanisms involved in the activation of DCs by HSV-1. We report that the release of pro-inflammatory cytokines by conventional DC (cDC during HSV-1 infection is triggered by both virus replication-dependent and replication-independent pathways. Interestingly, while vhs is capable of inhibiting the release of cytokines during infection of human and mouse cDCs, the secretion of cytokines by plasmacytoid DC (pDC is not affected by vhs. These data prompted us to postulate that infection of cDCs by HSV triggers a TLR independent pathway for cDC activation that is susceptible to blockage by the vhs protein. Using cDCs isolated from mice deficient in both the TLR adaptor protein MyD88 and TLR3, we show that HSV-1 and the vhs-deleted virus can activate cDCs independently of TLR signaling. In addition, virion-associated vhs fails to block cDC activation in response to treatment with TLR agonists, but it efficiently blocked cDC activation triggered by the paramyxoviruses Sendai Virus (SeV and Newcastle Disease Virus (NDV. This block to SeV- and NDV-induced activation of cDC resulted in elevated SeV and NDV viral gene expression indicating that infection with HSV-1 enhances the cell's susceptibility to other pathogens through the action of vhs. Our results demonstrate for the first time that a viral protein contained in the tegument of HSV-1 can block the induction of DC activation by TLR-independent pathways of viral recognition.

  2. FORMULATION AND DEVELOPMENT OF TOPICAL NIOSOMAL GEL OF BCS CLASS - III ANTI-VIRAL DRUG FOR BETTER EFFICACY AS HERPES TREATMENT

    Directory of Open Access Journals (Sweden)

    Modi Kushal A.

    2012-03-01

    Full Text Available The objective of present research work was to formulate niosomal gel of ACV and to evaluate it for enhancements of skin permeation and skin retention characteristics. ACV niosomes were prepared by classical thin layer hydration method. The niosomal vesicles were separated by centrifugation method and further evaluated for percentage drug entrapment (PDE and vesicle mean geometric diameter. The separated niosomal vesicles were incorporated into the Carbopol® 971 gel base. The niosomal gel was further evaluated for skin retention characteristics, in vitro diffusion study and stability studies at accelerated and non-accelerated conditions. The batch F12 was considered as optimized batch as it showed minimum geometric mean diameter of vesicles (1.23 ± 0.19 μm and maximum PDE (58.71 ± 0.89 %. The in vitro diffusion study using human cadaver skin (HCS showed 1.57 times higher flux as compared to conventional ACV gel. The skin retention study reveals that the percentage drug retained was 4.92 times higher as compared to conventional ACV gel. The stability studies at 2-8 °C showed PDE 94.23% after 12 weeks whereas at accelerated condition it was found to be 90.11%.

  3. Evaluation of the effects of acyclovir and/or human amniotic membrane on herpes virus culture and quantitative virus inactivity by real-time polymerase chain reaction

    Institute of Scientific and Technical Information of China (English)

    Feride; Aylin; Kantarci; Ali; Reza; Faraji; Aykut; Ozkul; Fikret; Akata

    2014-01-01

    ·AIM: To investigate the permeability of amniotic membrane in herpes virus cell culture to acyclovir with real time polymerase chain reaction(RT-PCR).·METHODS: Madin-Darby Bovine Kidney(MDBK) cell culture and Bovine Herpes Virus(BHV1) type 1 were used in the study. Cell cultures were grouped into two on the basis of herpes virus inoculation. Each group was sub-grouped into three. Amniotic membrane(V-HAM),acyclovir(V-A), and amniotic membrane and acyclovir(V-HAM-A) were applied to these subgroup cultures,respectively. After the application of the membrane and the drug, the cultures were evaluated at 24 and 48 h for cytopathic effect positive(CPE +) with a tissue culture microscope. In the CPE(+) samples, the DNA was extracted for viral DNA analysis by RT-PCR.·RESULTS: In control cultures without herpes virus CPE was not detected. Besides, amniotic membrane and acyclovir did not have cytotoxic effect on cell cultures.CPE were detected in Bovine Herpesvirus type-1inoculated cell cultures after amniotic membrane and/or acyclovir application. DNA analysis with RT-PCR indicated that Cycle threshold(Ct) values were lower in the BHV1 and membrane applied group(amniotic membrane group < acyclovir group < membrane and acyclovir group). This showed that membrane did not have antiviral effect. The membrane and acyclovir cell culture groups with high Ct values indicated thatmembrane was permeable and had a low barrier effect to drug.·CONCLUSION: In our in-vitro study, we found that amniotic membrane, which can be used in the treatment of corneal diseases, did not have antiviral effect. Besides,we detected that amniotic membrane was permeable to acyclovir in BHV-1 inoculated MDBK cell culture.However, more studies are necessary to investigate the quantitative effects of amniotic membrane and acyclovir.

  4. RA8, A human anti-CD25 antibody against human treg cells

    Energy Technology Data Exchange (ETDEWEB)

    Arias, Robyn; Flanagan, Meg; Miller, Keith D.; Nien, Yu-Chih; Hu, Peisheng; Gray, Dixon; Khawli, Leslie A.; Epstein, Alan L.

    2007-06-01

    Although anti-CD25 antibodies exist for clinical use in patients, there is a need for the development of a human Treg antibody that will abrogate the immunosuppressive function of this small but critical T cell subtype. Based upon mounting evidence that the level of Treg cells in the tumor microenvironment correlates with clinical prognosis and stage in man, it appears that Treg cells play an important role in the tumor's ability to overcome host immune responses. In mice, the rat anti-mouse CD25 antibody PC61 causes depletion of CD25-bearing Treg cells both peripherally in lymphatic tissues and in the tumor microenvironment, without inducing symptoms of autoimmunity. A similar antibody, though with the ability to delete Treg cells specifically, would be an important new tool for reversing tumor escape associated with Treg immunosuppression in man. To begin to generate such a reagent, we now describe the development of a human anti-CD25 antibody using a novel yeast display library. The target antigen CD25-Fc was constructed and used for five rounds of selection using a non-immune yeast display library that contained as many as 109 single chain variable fragments (scFv). Two unique clones with low KD values (RA4 and RA8) were then selected to construct fully human anti-CD25 antibodies (IgG1/kappa) for stable expression. One antibody, RA8, showed excellent binding to human CD25+ cell lines and to human Treg cells and appears to be an excellent candidate for the generation of a human reagent that may be used in man for the immunotherapy of cancer.

  5. Human anti-nucleolin recombinant immunoagent for cancer therapy.

    Science.gov (United States)

    Palmieri, Dario; Richmond, Timothy; Piovan, Claudia; Sheetz, Tyler; Zanesi, Nicola; Troise, Fulvia; James, Cindy; Wernicke, Dorothee; Nyei, Fata; Gordon, Timothy J; Consiglio, Jessica; Salvatore, Francesco; Coppola, Vincenzo; Pichiorri, Flavia; De Lorenzo, Claudia; Croce, Carlo M

    2015-07-28

    Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCL-dependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immune-based NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers. PMID:26170308

  6. Human anti-nucleolin recombinant immunoagent for cancer therapy

    Science.gov (United States)

    Palmieri, Dario; Richmond, Timothy; Piovan, Claudia; Sheetz, Tyler; Zanesi, Nicola; Troise, Fulvia; James, Cindy; Wernicke, Dorothee; Nyei, Fata; Gordon, Timothy J.; Consiglio, Jessica; Salvatore, Francesco; Coppola, Vincenzo; Pichiorri, Flavia; De Lorenzo, Claudia; Croce, Carlo M.

    2015-01-01

    Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCL-dependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immune-based NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers. PMID:26170308

  7. Herpes simplex type 2 pneumonia

    Directory of Open Access Journals (Sweden)

    Edenilson Eduardo Calore

    2002-12-01

    Full Text Available Extensive reviews of pulmonary infections in AIDS have reported few herpetic infections. Generally these infections are due to Herpes simplex type 1. Pneumonia due to herpes type 2 is extremely rare. We describe a 40 year-old HIV positive woman who complained of fever, cough and dyspnea for seven years. She had signs of heart failure and the appearance of her genital vesicles was highly suggestive of genital herpes. Echocardiography showed marked pulmonary hypertension, right ventricular hypertrophy and tricuspid insufficiency. After a few days of hospitalization she was treated with Aciclovir and later with Ganciclovir. An open pulmonary biopsy revealed an interstitial inflammation, localized in the alveolar walls. Some pulmonary arteries had widened walls and focal hyaline degeneration. Immunohistochemistry indicated that the nuclei had herpes simplex virus type 2 in many endothelial cells (including vessels with widened walls, macrophages in the alveolar septa and pneumocytes. There was clinical improvement after treatment for herpes. We concluded that as a consequence of herpes infection, endothelial involvement and interstitial inflammation supervene, with thickening of vascular walls and partial obliteration of the vessel lumen. A direct consequence of these changes in pulmonary vasculature was pulmonary hypertension followed by heart failure.

  8. Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS).

    Science.gov (United States)

    Hagiya, Hideharu; Iwamuro, Masaya; Tanaka, Takehiro; Hasegawa, Kou; Hanayama, Yoshihisa; Kimura, Maya; Otsuka, Fumio

    2016-01-01

    A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus (HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated. PMID:27374681

  9. 77 FR 5036 - Prospective Grant of Exclusive License: The Development of Human Anti-Mesothelin Monoclonal...

    Science.gov (United States)

    2012-02-01

    ... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: The Development of Human Anti-Mesothelin Monoclonal Antibodies for the Treatment of Human Cancers AGENCY: National..., Department of Health and Human Services, is contemplating the grant of an exclusive evaluation option...

  10. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

    NARCIS (Netherlands)

    Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

    2011-01-01

    Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

  11. 21 CFR 866.3305 - Herpes simplex virus serological assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Herpes simplex virus serological assays. 866.3305 Section 866.3305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal...

  12. Optimal management of genital herpes: current perspectives

    OpenAIRE

    Sauerbrei A

    2016-01-01

    Andreas Sauerbrei Institute of Virology and Antiviral Therapy, German Consulting Laboratory for Herpes Simplex Virus and Varicella-Zoster Virus, Jena University Hospital, Friedrich-Schiller University of Jena, Jena, Germany Abstract: As one of the most common sexually transmitted diseases, genital herpes is a global medical problem with significant physical and psychological morbidity. Genital herpes is caused by herpes simplex virus type 1 or type 2 and can manifest as primary and/or recurre...

  13. Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice

    Science.gov (United States)

    Cremer, Kenneth J.; Mackett, Michael; Wohlenberg, Charles; Notkins, Abner Louis; Moss, Bernard

    1985-05-01

    In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.

  14. Synthesis, Anti-Inflammatory and Anti-oxidant activity of some substituted Benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Rajasekaran S

    2012-09-01

    Full Text Available Benzimidazoles are an important class of compounds with a wide spectrum of biological activity ranging from anti-hypertensive, anti-viral, anti-fungal, antitumor and anthelmintic activity. In addition, few N-substituted benzimidazole derivatives have shown to exhibit significant activity against several viruses, including HIV, herpes simplex (HSV-1, influenza, picorna, human cytomegalovirus (HCMV and hepatitis C virus. The five membered heterocyclic moiety 1,3,4-oxadiazole also confers for various biological activity. Hence a series of benzimidazole derivatives fused with oxadiazole ring system have been synthesized, characterized by UV, IR and 1H NMR spectral data and evaluated for their in vitro and in vivo anti-inflammatory and antioxidant activity.

  15. Searching for the Human Herpes 6, 7 (PCR in CSF of Children Admitted to the Pediatric Ward of Hazrat Rasool Hospital of Tehran

    Directory of Open Access Journals (Sweden)

    F. Ebrahimi Taj

    2011-04-01

    Full Text Available Introduction & Objective: The role and frequency of HHV-6 and HHV-7 in central nervous system (CNS diseases of our children are unclear. The aim of this study was to search for the presence of HHV-6 & HHV-7 DNA-s in CSF samples in children with meningoencephalitis. Materials & Methods: In a cross- sectional study (2007-2009 done in the pediatric ward in Hazrat Rasoul hospital, Tehran ,Iran ,150 CSF samples were obtained from children with meningoencephalitis. The conventional and BACTEC Ped Plus medium; Latex agglutination tests; and in some cases bacterial PCR assay were used. We examined the DNA-s of HHV-6 & HHV-6 quantitavively by real time - PCR in the CSF samples. Results: Cases were 91 (60.7% male; 59 (39.3% female; 1-180 months old. Fever (>38.5 C was observed in 74%; irritability in 70% and convulsion in 53% of cases. All herpes viruses were detected in 18 (12% cases, HHV-6 DNA was detected in 6 cases and HHV-7 DNA detected in 2 cases with no correlation with age, sex and clinical signs. Conclusion: HHV-6 & HHV-7 were found in nearly 6% of all studied cases. HHV-6 was slightly more frequent than HHV-7 and its incidence is lower .Our data indicates that herpes viruses are not uncommon causes in children with meningoencephalitis. Our findings are different from those of previous studies perhaps due to the epidemiologic and geographic variations (differences in methods and age groups should be added to this. (Sci J Hamadan Univ Med Sci 2011;18(1:37-41

  16. Anti-galactose antibodies do not bind to normal human red cells

    International Nuclear Information System (INIS)

    The authors investigated the possibility that senescent cell IgG might have an anti-galactose (anti-gal) specificity as suggested by others. Anti-gal was isolated from normal human serum with α melibiose-agarose. The assays used were hemagglutination, rosetting, phagocytosis, and 125I protein A binding assay, immunoblotting, and glycine/HCL, pH 2.3, versus sugar elutions. Results revealed binding of anti-gal to rabbit but not human RBC. Immunoblotting of anti-gal revealed labeling of approx.29 bands in rabbit red cell membranes and no labeling of autologous human red cell membranes. The authors attempted to inhibit binding of anti-gal with various sugars. Melibiose caused enhancement rather than inhibition of agglutination when used at concentrations reported by previous investigators to cause inhibition. Neither α melibiose or galactose caused inhibition of phagocytosis of senescent cells. Senescent cell IgG was not displaced from freshly isolated old red cells by incubation with melibiose or galactose as determined by an 125I protein A binding assay. The authors were also unable to elute IgG from stored red cells with galactose. The authors conclude that senescent cell IgG does not have an anti-galactose specificity. The authors were unable to demonstrate an anti-gal antibody to normal human red cells

  17. Anti-galactose antibodies do not bind to normal human red cells

    Energy Technology Data Exchange (ETDEWEB)

    Kay, M.M.B.; Bosman, G.J.C.G.M.

    1986-03-01

    The authors investigated the possibility that senescent cell IgG might have an anti-galactose (anti-gal) specificity as suggested by others. Anti-gal was isolated from normal human serum with ..cap alpha.. melibiose-agarose. The assays used were hemagglutination, rosetting, phagocytosis, and /sup 125/I protein A binding assay, immunoblotting, and glycine/HCL, pH 2.3, versus sugar elutions. Results revealed binding of anti-gal to rabbit but not human RBC. Immunoblotting of anti-gal revealed labeling of approx.29 bands in rabbit red cell membranes and no labeling of autologous human red cell membranes. The authors attempted to inhibit binding of anti-gal with various sugars. Melibiose caused enhancement rather than inhibition of agglutination when used at concentrations reported by previous investigators to cause inhibition. Neither ..cap alpha.. melibiose or galactose caused inhibition of phagocytosis of senescent cells. Senescent cell IgG was not displaced from freshly isolated old red cells by incubation with melibiose or galactose as determined by an /sup 125/I protein A binding assay. The authors were also unable to elute IgG from stored red cells with galactose. The authors conclude that senescent cell IgG does not have an anti-galactose specificity. The authors were unable to demonstrate an anti-gal antibody to normal human red cells.

  18. Herpes zoster: A clinicocytopathological insight

    Directory of Open Access Journals (Sweden)

    Snehal Shah

    2016-01-01

    Full Text Available Herpes zoster or shingles is reactivation of the varicella zoster virus that had entered the cutaneous nerve endings during an earlier episode of chicken pox traveled to the dorsal root ganglia and remained in a latent form. This condition is characterized by occurrence of multiple, painful, unilateral vesicles and ulceration which shows a typical single dermatome involvement. In this case report, we present a patient with herpes zoster involving the mandibular division of the trigeminal nerve, with unilateral vesicles over the right side of lower third of face along the trigeminal nerve tract, with intraoral involvement of buccal mucosa, labial mucosa and the tongue of the same side. Cytopathology revealed classic features of herpes infection including inclusion bodies, perinuclear halo and multinucleated cells.

  19. Tumores perianais provocados pelo herpes simples Perianal tumors provoked by herpes simplex

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2007-03-01

    Full Text Available O Herpes simplex (HSV é um DNA vírus que provoca afecções perianais, sendo considerada a causa mais comum das úlceras na região. Apesar da forma ulcerativa ser a mais conhecida, a literatura relata o aparecimento de lesões tumorais, nodulares ou hipertróficas relacionadas ao vírus. O exame proctológico mostra tumores dolorosos, achatados, com superfície recoberta por ulceração rasa e com bordas bem delimitadas, elevadas e lobuladas, localizados na margem anal e/ou no sulco interglúteo, algumas vezes imitando condilomas virais ou carcinoma. A anamnese revela instalação insidiosa com crescimento lento e progressivo, além da história de tratamentos anteriores para úlceras herpéticas. O diagnóstico diferencial com carcinoma impõe a realização de biópsia para confirmação histológica. Esse exame revela hiperplasia epitelial moderada e denso processo inflamatório com linfócitos e plasmócitos. Células gigantes e multinucleadas são observadas na epiderme. Os testes imunohistoquímicos sugerem o HSV. A opção terapêutica inicial deve ser o tratamento medicamentoso. Importante definir o diagnóstico etiológico para aliviar o desconforto e evitar operação radical desnecessária, e introduzir medicação anti-retroviral nos portadores do HIV para melhora da imunidade.Herpes simplex is a DNA virus which provokes perianal lesions, and it is the most frequent etiology of anal ulcer. Despite the ulcerative herpes being known worldwide, literature relates a tumoral, or nodular, or hypertrophic form related to this virus. Proctological examination showed nodules with a verrucous appearance and an ulcerated surface at the anal margin, sometimes mimicking viral condylomas or carcinomas. Anamnesis reveals insidious installation, slow growth and prior treatments for herpetic ulcers. The differential diagnoses with cancer allow us to perform biopsies for histological confirmation. This exam reveals mild epithelial hyperplasia and

  20. Light chain editors of anti-DNA receptors in human B cells.

    Science.gov (United States)

    Kalinina, Olga; Wang, Yue; Sia, Kevin; Radic, Marko; Cazenave, Pierre-André; Weigert, Martin

    2014-02-10

    Receptor editing is a mechanism of self-tolerance used in newly generated B cells. The expressed heavy (H) or light (L) chain of an autoreactive receptor is replaced by upstream V genes which eliminate or modify autoreactivity. Editing of anti-DNA receptors has been characterized in anti-DNA transgenic mouse models including 3H9, 3H9/56R, and their revertant 3H9GL. Certain L chains, termed editors, rescue anti-DNA B cells by neutralizing or modifying DNA binding of the H chain. This editing mechanism acts on the natural H chain repertoire; endogenous H chains with anti-DNA features are expressed primarily in combination with editor L chains. We ask whether a similar set of L chains exists in the human repertoire, and if so, do they edit H chains with anti-DNA signatures? We compared the protein sequences of mouse editors to all human L chains and found several human L chains similar to mouse editors. These L chains diminish or veto anti-DNA binding when expressed with anti-DNA H chains. The human H chains expressed with these L chains also have relatively high arginine (Arg) content in the H chain complementarity determining region (H3), suggesting that receptor editing plays a role in establishing tolerance to DNA in humans.

  1. Expression of recombinant human anti-TNF-α scFv-Fc in Arabidopsis thaliana seeds.

    Science.gov (United States)

    Yao, N; Ai, L; Dong, Y Y; Liu, X M; Wang, D Z; Wang, N; Li, X W; Wang, F W; Li, Xk; Li, H Y; Jiang, C

    2016-01-01

    Recombinant human anti-tumor necrosis factor (TNF)-α scFv-Fc was expressed in TKO mutant Arabidopsis thaliana seeds using plant-specific codons. Immunoblotting using a human IgG1 antibody detected the expression of anti-TNF-α proteins in plants. Results from qRT-PCR analysis demonstrated that the time of harvest significantly affected the protein yield and quality. Our results indicate that the Phaseolus vulgaris β-phaseolin promoter directed anti-TNF-α scFv-Fc expression in A. thaliana seeds, with a maximum yield obtained at 20-days of development. Although the yield of anti-TNF-α scFv-Fc protein was not very high, accumulation of recombinant proteins in seeds is an attractive and simple method that can be used to purify biologically active anti-TNF-α scFv-Fc. PMID:27420937

  2. The seroprevalence of Kaposi′s sarcoma associated herpes virus and human herpes virus-6 in pediatric patients with cancer and healthy children in a Turkish pediatric oncology center

    Directory of Open Access Journals (Sweden)

    Nurdan Tacyildiz

    2014-01-01

    Full Text Available Background: Many studies have tried to be establish a pathogenic role for human herpesvirus-6 and -8 (HHV-6, HHV-8 in malignant diseases, but whether these viruses plays a role in these pathologies remains unclear. HHV-6 and HHV-8 seropositivity were shown in a healthy population. There is no published data in Turkey about seroprevalence of these viruses. We aimed to determine the seroprevalence of HHV-6 and HHV-8 in pediatric cancer patients and to compare with healthy Turkish children′s viral seroprevalence. Patients and Methods: Ninety-three pediatric cancer patients and 43 age-matched healthy children were included in the study. All sera were screened for antibodies to HHV-6 and HHV-8 by ELISA. Results: HHV-8 immunoglobulin G (IgG was positive in 3.3% of lymphoma patients, in 4.8% of acute lymphoblastic leukemia (ALL patients, in 4.8% of retinoblastoma patients and in 7% of healthy children. There was no significant difference in HHV-8 seroprevelance between these groups. HHV-6 seroprevalence was 81% in ALL patients, 70% in lymphoma group, 81% in retinoblastoma patients and 69.8% in healthy children. Although there was no significant difference in HHV-6 prevalence between healthy children and pediatric cancer patients, HHV-6 seropositivity tended to be higher in retinoblastoma patients under age of 4 years (odds ratio: 2.925. Conclusion: HHV-6 seroprevalence was higher than HHV-8 seropositivity in our study. Viral studies related HHV-6 seroprevelance in retinoblastoma patients would be useful to clarify if there is any etiological association between HHV-6 and retinoblastoma.

  3. Preparation of human cardiac anti-myosin: a review

    International Nuclear Information System (INIS)

    The present communication is a review of the physicochemical characterization and immunological properties of myosin isolated from the cardiac muscle, the production of monoclonal antibody anti-myosin, the radiolabeling of this antibody and its applications as radiopharmaceuticals to imaging myocardial infarcts. The classical example of radioimmunologic diagnosis of non malignant tissues is the detection of myocardial infarction by radiolabeled antibodies to myosin. (author)

  4. Atypical Herpes Zoster as a clinic begining of Acquired Immunodeficiency Syndrome. A case report

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Blanco Córdova

    2015-02-01

    Full Text Available The Herpes Zoster is produced by the reactivation of the Chicken Pox Zoster Virus. It has an incidence of three cases for each thousand inhabitants a year, and they increase the possibility to suffer it with the age. A 48 year old case of a patient with atypical Zoster with postherpetic neuralgia who came to the Dermatology consultation with cutaneous and mucous lesions is presented. This article has the objective to describe the evolution of the Herpes Zoster in the last patient diagnosed like seropositive to the virus of Human Immunodeficiency Virus It is considered of concern once both entities association was given, indicator that although Herpes Zoster incidence is low, considering the possible presence of diseases that involve the immune system. We conclude that in the presence of the clinical variety of Atypical Herpes Zoster, the coexistence of other diseases that compromise the immune system, as the Human Immunodeficiency Virus must be considered.

  5. Herpes: Removing Fact from Fiction.

    Science.gov (United States)

    Glover, Elbert D.

    1984-01-01

    Factual information dealing with the virus herpes is provided in hopes of allaying the public fears that have recently appeared because of misinformation presented by the media. Symptoms, types, and new developments in treatment are explored. Recommendations for obtaining additional information are offered. (DF)

  6. Acupuncture Treatment of Herpes Zoster

    Institute of Scientific and Technical Information of China (English)

    胡金生

    2001-01-01

    @@Case History Song××, a male middle school teacher aged 58 years, paid his first visit on August 7, 2000, with the chief complaint of pain in the left hypochondrium for 20 days. The patient stated that he suddenly got a sharp burning pain in the left hypochondrium in mid July. The pain gradually radiated to the upper abdominal area, meanwhile red herpes appeared in the hypochondriac region. He had been diagnosed as having herpes zoster, and treated in several nearby hospitals with fluid infusion and medication. As a result, the herpes partly disappeared. But the sharp burning pain still remained, which could not be relieved by administration of analgetics. The patient was then recommended by his friends for treatment here. The patient used to be in a anxious state of mind, and had a wiry pulse and disorder of the liver-qi. The patients had been disturbed by problems of his students and worried about his aged mother's illness, and had poor sleep. Physical examination showed that the patient had a slightly fat figure and sickly complexion, but was in a clear mind. His blood pressure was 140/90 mmHg, and heart rate 75 times/min. No abnormal signs were found in the heart and lungs. Prominent dark red herpes with obvious local tenderness was found on the skin surface of the left hypochondrium and upper abdome.

  7. Herpes simplex virus encephalitis in hamadan, iran.

    Directory of Open Access Journals (Sweden)

    Masoud Sabouri Ghannad

    2013-09-01

    Full Text Available Encephalitis can cause a severe public health problem. The main aim of this research was to evaluate the medical laboratory results of patients with Herpes Simplex Virus (HSV encephalitis.Diagnosis of encephalitis for these patients was firstly based on a clinical profile for Herpes Simplex Encephalitis (HSE, plus either a detected HSV1&2-DNA by PCR in CSF or brain neuro-imaging results.Molecular testing on CSF showed that 15 patients (15% had HSV infection, 5 patients (5% had Varicella Zoster Virus (VZV and one case was positive for Human Immunodeficiency Virus (HIV-RNA in CSF. The cause of encephalitis in 79 out of 100 patients (79% was unknown. The comparison of CSF analysis in HSV positives and negatives showed a significant increase of glucose and protein levels in HSV positives than negatives. The mortality rate was 46.6% (7/15 in patients with HSV encephalitis compared to 11.4% (10/85 in non-HSV encephalitis (P = 0.003.In the current study, 15% of cases were diagnosed as having HSV.

  8. Reactivation of herpes zoster along the trigeminal nerve with intractable pain after facial trauma: a case report and literature review

    OpenAIRE

    Lin, K-C; Wang, Che-Chuan; Wang, Kai-Yuan; Liao, Yi-Chen; Kuo, Jinn-Rung

    2009-01-01

    We report the rare occurrence of herpes zoster reactivation after facial trauma. Herpes zoster appeared in painful groups of distended vesicles containing clear fluid on an erythematous base within the secondary division of the trigeminal nerve. The patient was treated with acyclovir (intravenous, 250 mg, every 8 hours) combined with topical steroids and anti-neuropathic pain medication. The zoster-associated neuralgia subsided gradually 1.5 months after diagnosis. We illustrate this unique c...

  9. Urticaria from allergy to a purified human anti-Rh antibody preparation.

    Science.gov (United States)

    Sulakvelidze, I; Evans, S; Switzer, I; Underdown, B; Greenbaum, J; Dolovich, J

    1995-12-01

    This case presentation describes a young woman who developed generalized urticaria after receiving the human anti-RhD(D) preparation, WinRho, intravenously. Allergy skin tests and the radioallergosorbent test (RAST) for IgE antibodies to the human anti-D immunoglobulin preparation were positive. Further studies using high-pressure liquid chromatography and protein A column chromatography implicated a nonimmunoglobulin low-molecular-weight contaminant. This case report illustrates an allergic reaction to a highly purified human immunoglobulin preparation, and demonstrates approaches to assessment of such a reaction. PMID:8834828

  10. 76 FR 63317 - Prospective Grant of Exclusive License: The Development of Human Anti-Mesothelin Monoclonal...

    Science.gov (United States)

    2011-10-12

    ... monoclonal antibody m912 (SM-101) as an antibody therapy for the treatment of pancreatic cancer, ovarian... Human Anti-Mesothelin Monoclonal Antibodies for the Treatment of Human Cancers AGENCY: National... the antibody for the treatment of mesothelin-expressing cancers, including mesothelioma, lung...

  11. Radioimmunodetection of human leukemia with anti-interleukin-2 receptor antibody in severe combined immunodeficiency mice

    International Nuclear Information System (INIS)

    Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered 125I- and 111In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using 111In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL

  12. Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen Libo, E-mail: libochen888@hotmail.com [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Guo Guoying [Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018 (China); Liu Tianjing; Guo Lihe [Division of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Zhu Ruisen [Department of Nuclear Medicine, Shanghai Sixth People' s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2011-07-15

    Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene. Methods: HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay. Results: HepG2/NTG cells concentrated {sup 125}I{sup -} up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T{sub 1/2eff} of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or {sup 131}I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%{+-}2.5%, 43.4%{+-}2.8% and 8.6%{+-}1.2% after exposure to {sup 131}I, GCV and combined therapy, respectively. Conclusion: We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.

  13. Prospective Design of Anti-Transferrin Receptor Bispecific Antibodies for Optimal Delivery into the Human Brain.

    Science.gov (United States)

    Kanodia, J S; Gadkar, K; Bumbaca, D; Zhang, Y; Tong, R K; Luk, W; Hoyte, K; Lu, Y; Wildsmith, K R; Couch, J A; Watts, R J; Dennis, M S; Ernst, J A; Scearce-Levie, K; Atwal, J K; Ramanujan, S; Joseph, S

    2016-05-01

    Anti-transferrin receptor (TfR)-based bispecific antibodies have shown promise for boosting antibody uptake in the brain. Nevertheless, there are limited data on the molecular properties, including affinity required for successful development of TfR-based therapeutics. A complex nonmonotonic relationship exists between affinity of the anti-TfR arm and brain uptake at therapeutically relevant doses. However, the quantitative nature of this relationship and its translatability to humans is heretofore unexplored. Therefore, we developed a mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model for bispecific anti-TfR/BACE1 antibodies that accounts for antibody-TfR interactions at the blood-brain barrier (BBB) as well as the pharmacodynamic (PD) effect of anti-BACE1 arm. The calibrated model correctly predicted the optimal anti-TfR affinity required to maximize brain exposure of therapeutic antibodies in the cynomolgus monkey and was scaled to predict the optimal affinity of anti-TfR bispecifics in humans. Thus, this model provides a framework for testing critical translational predictions for anti-TfR bispecific antibodies, including choice of candidate molecule for clinical development. PMID:27299941

  14. Clinical Presentation of Atypical Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    李俊杰; 梁沛杨; 罗北京

    2002-01-01

    Objective: To make a clinical analysis on the basis of 36cases of atypical genital herpes (GH) patients. Methods: Thirty-six cases of atypical GH were diagnosedclinically, and their case histories, symptoms and signs wererecorded in detail and followed up. Polymerase chain reaction(PCR) was adopted for testing HSV2-DNA with cotton-tippedswabs. Enzyme-linked immuno sorbent assay (ELISA) forserum anti-HSV2-IgM was done to establish a definfiivediagnosis. Other diagnoses were excluded at the same time bytesting for related pathogens including fungi, Chlamydia,Mycoplasma, Treponema pallidum, gonococci, Trichomonas,etc. Results: The main clinical manifestations of atypical GHwere: (1) small genital ulcers; (2) inflammation of urethralmeatus; (3) nonspecific genital erythema; (4) papuloid noduleson the glands; (5) nonspecific vaginitis. Twenty-three cases(64%) tested by PCR were HSV2-DNA sera-positive, and 36cases (100 %) anti-HSV2-IgM sera-positive by ELISA. Conclusion: atypical HSV is difficult to be diagnosed. Butthe combination of PCR and ELIAS will be helpful to thediagnosis of atypical HSV.

  15. ANTI-HYPOXIA AND ANTI-OXIDATION EFFECTS OF AMINOPHYLLINE ON HUMAN WITH ACUTE HIGH-ALTITUDE EXPOSURE

    Institute of Scientific and Technical Information of China (English)

    Bo Yang; Guang-yi Wang; Bin Chen; Rong-bin Qin; Si Lang Zha Xi; Lian Chen

    2007-01-01

    Objective To investigate the anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure.Methods Totally 100 young male army members newly recruited from Sichuan province (400 meters above sea level) were enrolled. They were randomly divided into two groups; 50 in aminophylline group (A group) and 50 in control group (C group). A group and C group orally took aminophylline and placebo respectively for 10 days, 7 days before entering Lhasa (3 658 meters above sea level) by air and 3 days after it Several parameters were measured at three time points: before drug taken, 7 days after drug taken, and 3 days after ascending high altitude. These parameters included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen saturation (SO2) , arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare the difference between two groups with Stata 7.0 software system.Results There were no statistical differences between groups in hypoxia and oxidation indicators before and after drug taken in plain area. Three days after ascending high altitude, the serum levels of SOD, CAT, H2O2, LA, PaCO2 increased in both groups, yet to a much larger degree in C group than A group (P < 0.01); and NO, SO2, PaO2 decreased more markedly in C group (P < 0.05 for NO, P < 0.0001 for SO2 and PaO2).Conclusion Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.

  16. Herpes and papilloma viruses

    Energy Technology Data Exchange (ETDEWEB)

    De Palo, G.; Rilke, F.; Zur Hausen, H.

    1986-01-01

    This book contains over 25 selections. Some of the titles are: Seroepidemiologic Asociation of HSV-2 with Cervical Cancers: Transforming Viral Genes; Organization and Expression of Human Papillomavirus DNA in Cervical Cancer Cell Lines; An Investigation of Cervical Scrapes by DNA Hybridization: and Human Papillomaviruses in Genital Tissue: Examination by Immunohistochemistry and in situ DNA Hybridization.

  17. Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Edouard Matevossian

    2008-03-01

    Full Text Available Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative.

  18. Polyneuritis cranialis following herpes zoster

    Directory of Open Access Journals (Sweden)

    Radhakrishna H

    2000-01-01

    Full Text Available Herpes zoster is a common clinical condition involving cranial nerves. We encountered 3 cases in which multiple cranial nerves were involved besides the commoner ones. All the three cases were treated with acyclovir and oral steroids. Recovery of motor function was only partial in all three cases when reviewed 2 months after discharge. The clinical details and a brief review of literature are presented.

  19. Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex.

    Science.gov (United States)

    Moodley, Kogie; Botha, Julia; Raidoo, Deshandra Munsamy; Naidoo, Strinivasen

    2011-03-15

    Expression of thyroid-stimulating hormone receptor (TSH-R) has been demonstrated in adipocytes, lymphocytes, bone, kidney, heart, intestine and rat brain. Immuno-reactive TSH-R has been localised in rat brain and human embryonic cerebral cortex but not in adult human brain. We designed a pilot study to determine whether anti-thyroid auto-antibodies immuno-localise in normal adult human cerebral cortex. Forensic samples from the frontal, motor, sensory, occipital, cingulate and parieto-occipito-temporal association cortices were obtained from five individuals who had died of trauma. Although there were no head injuries, the prior psychiatric history of patients was unknown. The tissues were probed with commercial antibodies against both human TSH-R and human thyroglobulin (TG). Anti-TSH-R IgG immuno-localised to cell bodies and axons of large neurones in all 6 regions of all 5 brains. The intensity and percentage of neurones labelled were similar in all tissue sections. TSH-R immuno-label was also observed in vascular endothelial cells in the cingulate gyrus. Although also found in all 5 brains and all six cortical regions, TG localised exclusively in vascular smooth muscle cells and not on neurones. Although limited by the small sample size and number of brain areas examined, this is the first study describing the presence of antigenic targets for anti-TSH-R IgG on human cortical neurons, and anti-TG IgG in cerebral vasculature. PMID:21196016

  20. Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer.

    Science.gov (United States)

    Bhutia, Sujit K; Behera, Birendra; Nandini Das, Durgesh; Mukhopadhyay, Subhadip; Sinha, Niharika; Panda, Prashanta Kumar; Naik, Prajna Paramita; Patra, Samir K; Mandal, Mahitosh; Sarkar, Siddik; Menezes, Mitchell E; Talukdar, Sarmistha; Maiti, Tapas K; Das, Swadesh K; Sarkar, Devanand; Fisher, Paul B

    2016-07-15

    Abrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki-67 and CD-31, respectively. In addition, TUNEL positive cells increased in breast tumors treated with AGG suggesting that AGG mediates anti-tumorigenic activity through induction of apoptosis and inhibition of angiogenesis. On a molecular level, AGG caused extrinsic apoptosis through ROS generation that was AKT-dependent in breast cancer cells, without affecting primary mammary epithelial cells, suggesting potential cancer specificity of this natural compound. In addition, using HUVECs, AGG inhibited expression of the pro-angiogenic factor IGFBP-2 in an AKT-dependent manner, reducing angiogenic phenotypes both in vitro and in vivo. Overall, the present results establish that AGG promotes both apoptosis and anti-angiogenic activities in human breast tumor cells, which might be exploited for treatment of breast and other cancers. PMID:26914517

  1. Screening of Fungi from Chinese Medical Plants for Anti-Human Immunodeficiency Virus Type 1 Activity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to isolate anti-human immunodeficiency virus (HIV) agents from natural products, 97 ethanolic extracts of 90 fungi were tested for their inhibitory activity on HIV-1. Most of the extracts tested were relatively non-toxic to human lymphocytic MT-4 cells, but extracts of some fungi exhibited potent anti-HIV activity in an in vitro 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay with a selectivity index greater than 3. Most fungi were isolated from Dendrobium sp. and Taxus sp.

  2. Infection with an H2 recombinant herpes simplex virus vector results in expression of MHC class I antigens on the surfaces of human neuroblastoma cells in vitro and mouse sensory neurons in vivo.

    Science.gov (United States)

    Abendroth, A; Simmons, A; Efstathiou, S; Pereira, R A

    2000-10-01

    The majority of neurons in herpes simplex virus (HSV)-infected murine sensory ganglia are transiently induced to express MHC-I antigens at the cell surface, whereas only a minority are themselves productively infected. The aim of the current work was to determine whether MHC-I antigens can be expressed on the surfaces of infected neurons in addition to their uninfected neighbours. To address this aim a recombinant HSV type 1 strain, S-130, was used to deliver a mouse H2K(d) gene, under control of the HCMV IE-1 promoter/enhancer, into human neuroblastoma cells in vitro and mouse primary sensory neurons in vivo. S-130 expressed H2K(d) antigens on the surfaces of IMR-32 cells, a human neuroblastoma cell line that expresses very low levels of MHC-I constitutively. In K562 cells, which do not express MHC-I constitutively, H2K(d) and beta(2)-microglobulin (beta(2)m) were shown to be co-expressed at the cell surface following S-130 infection. This observation was taken as evidence that class I heavy chain (alphaC) molecules encoded by the expression cassette in the HSV genome were transported to the cell surface as stable complexes with beta(2)m. Significantly, after introduction of S-130 into flank skin, H2K(d) antigens were detected on the surfaces of primary sensory neurons in ganglia innervating the inoculation site. Our data show that HSV-infected murine primary sensory neurons and human neuroblastoma cells are capable of expressing cell-surface MHC-I molecules encoded by a transgene. From this, we infer that up-regulation of alphaC expression is, in principle, sufficient to overcome potential impediments to neuronal cell surface expression of MHC-I complexes.

  3. Susceptibility of herpes simplex virus isolated from genital herpes lesions to ASP2151, a novel helicase-primase inhibitor.

    Science.gov (United States)

    Katsumata, Kiyomitsu; Weinberg, Adriana; Chono, Koji; Takakura, Shoji; Kontani, Toru; Suzuki, Hiroshi

    2012-07-01

    ASP2151 (amenamevir) is a helicase-primase inhibitor against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. To evaluate the anti-HSV activity of ASP2151, susceptibility testing was performed on viruses isolated from patients participating in a placebo- and valacyclovir-controlled proof-of-concept phase II study for recurrent genital herpes. A total of 156 HSV strains were isolated prior to the dosing of patients, and no preexisting variants with less susceptibility to ASP2151 or acyclovir (ACV) were detected. ASP2151 inhibited HSV-1 and HSV-2 replication with mean 50% effective concentrations (EC(50)s) of 0.043 and 0.069 μM, whereas ACV exhibited mean EC(50)s of 2.1 and 3.2 μM, respectively. Notably, the susceptibilities of HSV isolates to ASP2151 and ACV were not altered after dosing with the antiviral agents. Taken together, these results demonstrate that ASP2151 inhibits the replication of HSV clinical isolates more potently than ACV, and HSV resistant to this novel helicase-primase inhibitor as well as ACV may not easily emerge in short-term treatment for recurrent genital herpes patients.

  4. Recurrent facial urticaria following herpes simplex labialis

    Directory of Open Access Journals (Sweden)

    Vijay Zawar

    2012-01-01

    Full Text Available We describe recurrent acute right-sided facial urticaria associated with herpes labialis infection in a middle-aged female patient. Antiviral medications and antihistamines not only successfully cleared the herpes infection and urticaria but also prevented further recurrences.

  5. Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in the pericardium: A case with latency type III Epstein-Barr virus infection showing good prognosis without chemotherapy.

    Science.gov (United States)

    Nakamura, Harumi; Tsuta, Koji; Nakagawa, Takashi; Hirai, Risen; Ota, Yasunori

    2015-12-01

    Primary effusion lymphoma (PEL) is a rare subtype of non-Hodgkin lymphoma that proliferates in body cavities without detectable masses. PEL is universally associated with human herpes virus-8 (HHV-8) infection and has an aggressive prognosis. Recently, an HHV-8-unrelated PEL-like lymphoma that usually occurs in elderly individuals and follows a more indolent prognosis has been reported, and it is treated as a disease distinct from PEL. However, its pathogenesis and prognostic factors have not been sufficiently clarified. In PEL-like lymphoma accompanied by Epstein-Barr virus (EBV) infection, latent infection types are not mentioned in the literature. Herein, we report the case of an 85-year-old Japanese man with pericardial PEL-like lymphoma who showed good improvement in condition for 24 months after pericardiocentesis without chemotherapy. Serological test results were positive for EBV capsid antigen and EBV nuclear antigen 2 (EBNA2), but negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. The disease phenotype and EBV infection mechanism were immunohistochemically investigated by the cellblock prepared from pericardial effusion. Atypical cells were positive for CD20, CD30, CD45, BCL2, MUM1, EBNA2, latent membrane protein 1, and EBV-encoded RNA (on in situ hybridization), but negative for CD3, CD5, CD10, CD138, cytokeratin AE1/AE3, and HHV-8. Accordingly, this case was considered to be a B-cell activated phenotype with a type III latent EBV infection. Type III latent EBV infection is unusual in PEL. PMID:26384578

  6. Hereditary orotic aciduria, Lesch-Nyhan syndrome, and xeroderma pigmentosum probed by herpes simplex virus: /sup 125/I-iododeoxycytidine incorporation as an assay for viral growth. [Human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Campisi, J.; Hafner, J.; Boorstein, R.; Pardee, A.B.

    1983-01-01

    /sup 125/I-Iododeoxycytidine (/sup 125/IdC) incorporation into acid-insoluble material was a sensitive, rapid, and quantitative assay for the growth of herpes simplex virus type 1 (HSV-1) in human fibroblasts. Cellular utilization of the isotope was 10 to 25% of the incorporation by infected cells and could be 80% inhibited by tetrahydrouridine (THU). Viral utilization was inhibited by acycloguanosine, thioguanine (TG), and cytosine arabinoside. Isotope was incorporated equally well by growing or quiescent infected cells. HSV-1 was used to probe the metabolic capabilities of three mutant human fibroblast strains. /sup 125/IdC incorporation quantitatively measured the ability of the virus to grow in these cells. Viral /sup 125/IdC incorporation was sensitive to TG in normal fibroblasts but showed a 8- to 10-fold greater resistance to TG in fibroblasts derived from patients with Lesch-Nyhan syndrome (LN). Similarly, the growth of ultraviolet irradiated HSV-1 in normal fibroblasts was 5-fold greater than in fibroblasts derived from patients with xeroderma pigmentosum. In fibroblasts derived from patients with hereditary orotic aciduria, viral /sup 125/IdC incorporation was sensitive to adenosine (AD) at concentrations which were slightly stimulatory in normal fibroblasts. This was a 2-fold difference in AD sensitivity, which the radioassay reliably and quantitatively documented. HSV-1 infected cells could be individually identified by their incorporated /sup 125/IdC; such cells had blackened nuclei in autoradiograms prepared 12 hr after infection. Normal cells infected in the presence of TG had many fewer labeled nuclei than LN cells similarly infected in the presence of the drug. (JMT)

  7. Identification of human herpes virus in blood donors by nested-polymerase chain reaction%巢式聚合酶链反应检测人疱疹病毒在人群中的感染情况∗

    Institute of Scientific and Technical Information of China (English)

    李明月; 李凌云; 沈曦月; 周帅; 罗笛; 巢嘉婧; 冯纯; 姚堃; 冯东举; 周锋

    2015-01-01

    目的:调查人群中人疱疹病毒(HHV),包括人巨细胞病毒(HCMV)、EB病毒(EBV)、HHV-6和 HHV-7的感染情况。方法收集55例南京市无偿献血者的外周血标本,提取全血DNA,巢氏PCR扩增 HCMV、EBV、HHV-6和 HHV-7特异性序列,1%琼脂糖凝胶电泳鉴定。结果55例献血者中 EBV、HCMV、HHV-6和 HHV-7的阳性感染率分别为50.9%、5.5%、49.1%和21.8%,并且存在多种病毒混合感染。结论 HHV筛查对临床相关疾病的诊治具有十分重要的意义,应引起医务工作者的重视。%Objective To investigate the prevalence of four kinds of human herpes viruses (HHV)in the blood of blood donors, including human cytomegalovirus (HCMV),epstein-barr virus (EBV),HHV-6,HHV-7.Methods DNA was prepared in whole blood samples collected from 55 blood donors.The presence of DNA of EBV,HCMV,HHV-6,HHV-7 were examined by specific nested-polymerase chain reaction.Results Prevalence of EBV,HCMV,HHV-6 and HHV-7 in whole blood were 50.9%,5.5%, 49.1% and 21.8% respectively.Multi-infections were observed in some objects.Conclusion The examination of HHV infection is useful in diagnosis and treatment of HHV related disease.

  8. Low Prevalence of Varicella Zoster Virus and Herpes Simplex Virus Type 2 in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

    Science.gov (United States)

    Wang, Chunmei C.; Yepes, Luis C.; Danaher, Robert J.; Berger, Joseph R.; Mootoor, Yunanan; Kryscio, Richard J.; Miller, Craig S.

    2009-01-01

    Objectives Human herpesviruses (HHVs), e.g. herpes simplex virus (HSV) type 1, Epstein-Barr virus and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva during this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence and amounts of VZV and HSV-2 in the saliva of HIV-infected, orally asymptomatic patients. Study Design Quantitative polymerase chain reaction was used to investigate the prevalence, quantity, risk, and correlates of salivary VZV and HSV-2 from 59 HIV-seropositive individuals and 53 healthy controls in a case-control, cross-sectional study. Seventy-eight percent of the HIV-seropositive patients (46/59) were taking HAART. Results VZV DNA was detected in the saliva of 5.1% (3/59) of the HIV-positive group and in only one healthy control 1.9% (1/53; P = 0.62). The amount of VZV DNA in the expressors was low, generally less than 1,100 copies/mL with no observed difference between the HIV-positive group and the controls (P= 1.0). HSV-2 DNA was not detected in either group. In the HIV-infected group, VZV shedding occurred in those on HAART, but was not associated with oral lesions, specific CD4+ or CD8+ T-cell levels, or demographic factors. Conclusions VZV was detected at low prevalence in the saliva of HIV-infected persons whereas HSV-2 was not detected in the saliva of this cohort. HAART does not appear to diminish the risk for asymptomatic VZV shedding. PMID:20123407

  9. Do there exist synergistic antitumor effects by coexpression of herpes simplex virus thymidine kinase with cytokine genes on human gastric cancer cell line SGC7901?

    Institute of Scientific and Technical Information of China (English)

    Jian-Hua Zhang; Ming-Xi Wan; Jia-Ying Yuan; Bo-Rong Pan

    2004-01-01

    AIM: To evaluate the synergistic antitumor effects of herpes simplex virus thymidine kinase (HSV-TK) together with tumor necrosis factor alpha (TNF-α) or interleukin-2 (IL-2) gene expression on gastric cancer cell line SGC7901.METHODS: Recombinant vectors pL(TT)SN and pL(TI)SN,which express TK-IRES-TNF-α and TK-IRES-IL-2 genes separately, as well as the control plasmids pL(TK)SN and pLXSN were employed to transfect PA317 cells respectively to generate the viruses that can stably express the objective genes through G418 selection. The gastric cancer cells were then transfected by the retroviral serum from the package cells and maintained in culture to determine the cell growth and apoptosis. The cytotoxic effects of HSV-TK together with TNF-α or IL-2 gene expression on the transfected cancer cells were evaluated by the cell viability and bystander effects in the presence of GCV supplemented in the cultural medium.RESULTS: Expression of recombinant proteins including TNF-α and IL-2 by stable transfectants was confirmed by Western blotting. The percentage of cell apoptosis in the SGC/0, SGC/TK-TNF-α, SGC/TK-IL-2 and SGC/TK clone was 2.3%, 12.3%, 11.1% and 10.9% respectively at 24 h posttransfection. Cell growth status among all the experimental groups as judged by cell absorbance (,4) at 570nm did not exhibit any significant difference (P>0.05); although it was noted to be slightly lower in the SGC/-TT group. Cell survival rate in SGC/TI, SGC/TT and SGC/TK group was significantly decreased in a dose-dependent manner of GCV compared with that of the SGC/0 group (P<0.05-0.01). Among all studied cells, the SGC/TTm was shown most sensitive to GCV rate of SGC/0 cells was not affected by the presence of GCV bystander effect induced by SGC/TI, SGC/TT- and SGC/TK cells was confirmed by the fact that 20% of these stable transfectants could kill 50% of the co-cultured cells, in which the most prominent bystander effect was found in the circumstance of SGC/TTF presence

  10. Functional in vitro studies of recombinant human immunoglobulin G and immunoglobulin A anti-D

    DEFF Research Database (Denmark)

    Nielsen, Leif Kofoed; Green, Trine Hefsgaard; Norderhaug, Lars;

    2007-01-01

    The use of anti-D purified from human serum to prevent hemolytic disease of the fetus and newborn due to D is well established. Owing to supply and safety reasons, however, an unlimited and non-plasma-derived source of antibodies for Rhesus prophylaxis is needed....

  11. Molecular mechanisms of anti-aging hormetic effects of mild heat stress on human cells

    DEFF Research Database (Denmark)

    Rattan, Suresh I S; Eskildsen-Helmond, Yvonne E G; Beedholm, Rasmus

    2004-01-01

    In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. We have reported the hormetic effects of repeated challenge...

  12. Normally Occurring Human Anti-GM1 Immunoglobulin M Antibodies and the Immune Response to Bacteria

    OpenAIRE

    Alaniz, María E.; Lardone, Ricardo D.; Yudowski, Silvia L.; Farace, María I.; Nores, Gustavo A.

    2004-01-01

    Anti-GM1 antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children

  13. Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector.

    Science.gov (United States)

    Taylor, Travis J; Diaz, Fernando; Colgrove, Robert C; Bernard, Kristen A; DeLuca, Neal A; Whelan, Sean P J; Knipe, David M

    2016-09-01

    West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus.

  14. Human posterior parietal cortex encodes the movement goal in a pro-/anti-reach task

    OpenAIRE

    Gertz, Hanna; Fiehler, Katja

    2015-01-01

    Previous research on reach planning in humans has implicated a frontoparietal network, including the precuneus (PCu), a putative human homolog of the monkey parietal reach region (PRR), and the dorsal premotor cortex (PMd). Using a pro-/anti-reach task, electrophysiological studies in monkeys have demonstrated that the movement goal rather than the location of the visual cue is encoded in PRR and PMd. However, if only the effector but not the movement goal is specified (underspecified conditi...

  15. Sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses.

    Science.gov (United States)

    Limsuwat, Nattavatchara; Suptawiwat, Ornpreya; Boonarkart, Chompunuch; Puthavathana, Pilaipan; Wiriyarat, Witthawat; Auewarakul, Prasert

    2016-03-01

    It was shown previously that human saliva has higher antiviral activity against human influenza viruses than against H5N1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic-acid-containing molecules. To further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza A and B virus, pandemic H1N1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and chicken saliva. Human saliva showed higher hemagglutination inhibition (HI) and neutralization (NT) titers against seasonal influenza A virus and the pandemic H1N1 viruses than against influenza B virus and most avian influenza viruses, except for H9N2 and H12N9 avian influenza viruses, which showed high HI and NT titers. To understand the nature of sialic-acid-containing anti-influenza factors in human saliva, α2,3- and α2,6-linked sialic acid was measured in human saliva samples using a lectin binding and dot blot assay. α2,6-linked sialic acid was found to be more abundant than α2,3-linked sialic acid, and a seasonal H1N1 influenza virus bound more efficiently to human saliva than an H5N1 virus in a dot blot analysis. These data indicated that human saliva contains the sialic acid type corresponding to the binding preference of seasonal influenza viruses.

  16. Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Vestergaard, B F

    1991-01-01

    infection in nanomolar-micromolar concentrations, but no anti-HIV effect was found with the lectin HPA, mainly reacting with O-linked oligosaccharides. HSV-1 infectivity was measured in a plaque reduction assay using Vero cells, and while both N- and O-linked oligosaccharide -specific lectins inhibited HSV......-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses....

  17. Human recombinant RNASET2: A potential anti-cancer drug

    Science.gov (United States)

    Roiz, Levava; Smirnoff, Patricia; Lewin, Iris; Shoseyov, Oded; Schwartz, Betty

    2016-01-01

    The roles of cell motility and angiogenetic processes in metastatic spread and tumor aggressiveness are well established and must be simultaneously targeted to maximize antitumor drug potency. This work evaluated the antitumorigenic capacities of human recombinant RNASET2 (hrRNASET2), a homologue of the Aspergillus niger T2RNase ACTIBIND, which has been shown to display both antitumorigenic and antiangiogenic activities. hrRNASET2 disrupted intracellular actin filament and actin-rich extracellular extrusion organization in both CT29 colon cancer and A375SM melanoma cells and induced a significant dose-dependent inhibition of A375SM cell migration. hrRNASET2 also induced full arrest of angiogenin-induced tube formation and brought to a three-fold lower relative HT29 colorectal and A375SM melanoma tumor volume, when compared to Avastin-treated animals. In parallel, mean blood vessel counts were 36.9% lower in hrRNASET2-vs. Avastin-treated mice and survival rates of hrRNASET2-treated mice were 50% at 73 days post-treatment, while the median survival time for untreated animals was 22 days. Moreover, a 60-day hrRNASET2 treatment period reduced mean A375SM lung metastasis foci counts by three-fold when compared to untreated animals. Taken together, the combined antiangiogenic and antitumorigenic capacities of hrRNASET2, seemingly arising from its direct interaction with intercellular and extracellular matrices, render it an attractive anticancer therapy candidate. PMID:27014725

  18. Anti-Infectious Human Vaccination in Historical Perspective.

    Science.gov (United States)

    D'Amelio, Enrico; Salemi, Simonetta; D'Amelio, Raffaele

    2016-05-01

    A brief history of vaccination is presented since the Jenner's observation, through the first golden age of vaccinology (from Pasteur's era to 1938), the second golden age (from 1940 to 1970), until the current period. In the first golden age, live, such as Bacille Calmette Guérin (BCG), and yellow fever, inactivated, such as typhoid, cholera, plague, and influenza, and subunit vaccines, such as tetanus and diphtheria toxoids, have been developed. In the second golden age, the cell culture technology enabled polio, measles, mumps, and rubella vaccines be developed. In the era of modern vaccines, in addition to the conjugate polysaccharide, hepatitis A, oral typhoid, and varicella vaccines, the advent of molecular biology enabled to develop hepatitis B, acellular pertussis, papillomavirus, and rotavirus recombinant vaccines. Great successes have been achieved in the fight against infectious diseases, including the smallpox global eradication, the nearly disappearance of polio, the control of tetanus, diphtheria, measles, rubella, yellow fever, and rabies. However, much work should still be done for improving old vaccines, such as BCG, anthrax, smallpox, plague, or for developing effective vaccines against old or emerging infectious threats, such as human-immunodeficiency-virus, malaria, hepatitis C, dengue, respiratory-syncytial-virus, cytomegalovirus, multiresistant bacteria, Clostridium difficile, Ebola virus. In addition to search for innovative and effective vaccines and global infant coverage, even risk categories should adequately be protected. Despite patients under immunosuppressive therapy are globally increasing, their vaccine coverage is lower than recommended, even in developed and affluent countries. PMID:26606466

  19. Linfomas asociados con la infección por el virus de la inmunodeficiencia humana: subtipos histológicos y asociación con los virus de Epstein Barr y Herpes-8 AIDS related lymphomas: Histopathological subtypes and association with Epstein Barr virus and Human Herpes virus type-8

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2010-04-01

    Full Text Available Los linfomas no Hodgkin (LNH constituyen la segunda neoplasia definitoria de Sida más frecuente. En el presente trabajo se evaluaron 48 casos de linfomas asociados con la enfermedad debida al virus de la inmunodeficiencia humana (HIV diagnosticados en la División Histopatología del Instituto de Investigaciones Hematológicas de la Academia Nacional de Medicina. Se incluyeron en la investigación 5 mujeres y 43 hombres con una mediana de edad al momento del diagnóstico de la neoplasia de 37 años. La evaluación morfológica se realizó en cortes coloreados con hematoxilina-eosina, estudio inmunohistoquímico para la detección del virus de Epstein Barr (VEB en 48/48 casos, y mediante sonda oligonucleotídica biotinilada para la detección del ADN del Herpes virus humano tipo-8 (HHV-8 en 14/14 linfomas plasmoblásticos (LP. Todos fueron linfomas de fenotipo B, con un curso clínico agresivo y enfermedad neoplásica avanzada al momento del diagnóstico. Se pudo demostrar la fuerte asociación del VEB con los linfomas asociados al sida, con frecuencias que variaron según el subtipo histológico: 16/21 (76% para los linfomas difusos de grandes células; 1/3 casos (33% de linfomas de Burkitt y 3/4 (75% en los linfomas primarios del sistema nervioso central. Globalmente, el genoma del VEB se detectó en 20/28 (71% de las muestras de biopsias de LNH de esta serie. La detección del HHV-8 resultó negativa en los 14 LP. Los linfomas de Hodgkin fueron más frecuentes en varones,18/20 (90%, con un curso clínico agresivo y franco predominio de los subtipos histológicos de peor pronóstico (90% de casos. En estas neoplasias también se comprobó una frecuente asociación patogénica con el VEB (90% de casos.Non-Hodgkin lymphomas (NHL of the B-cell type are the second most common neoplasm among patients with human immunodeficiency virus (HIV infection and AIDS. Here, we evaluated 48 cases of AIDS-related lymphomas (ARL diagnosed at the

  20. Clinical significance of "anti-HBc alone" in human immunodeficiency virus-positive patients

    Institute of Scientific and Technical Information of China (English)

    Ma Teresa Pérez-Rodríguez; Bernardo Sope(n)a; Manuel Crespo; Alberto Rivera; Teresa Gonzólez del Blanco; Antonio Ocampo; César Martínez-Vázquez

    2009-01-01

    AIM: To determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection ("anti-HBc alone") among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated.METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients.RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (CI) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups.Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA.CONCLUSION: "Anti-HBc alone" prevalence in HIVpositive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury.

  1. Inflammatory Kinetics and Efficacy of Anti-inflammatory Treatments on Human Nucleus Pulposus Cells

    Science.gov (United States)

    Walter, Benjamin A; Purmessur, Devina; Likhitpanichkul, Morakot; Weinberg, Alan; Cho, Samuel K.; Qureshi, Sheeraz A.; Hecht, Andrew C.; Iatridis, James C.

    2015-01-01

    Study Design Human nucleus pulposus (NP) cell culture study investigating response to tumor necrosis factor-α (TNFα), effectiveness of clinically available anti-inflammatory drugs, and interactions between pro-inflammatory cytokines. Objective To characterize the kinetic response of pro-inflammatory cytokines released by human NP cells to TNFα stimulation and the effectiveness of multiple anti-inflammatories with 3 sub-studies: Timecourse, Same-time blocking, Delayed blocking. Summary of Background Data Chronic inflammation is a key component of painful intervertebral disc (IVD) degeneration. Improved efficacy of anti-inflammatories requires better understanding of how quickly NP cells produce pro-inflammatory cytokines and which pro-inflammatory mediators are most therapeutically advantageous to target. Methods Degenerated human NP cells (n=10) were cultured in alginate with or without TNFα (10ng/mL). Cells were incubated with one of four anti-inflammatories (anti-IL-6 receptor/atlizumab, IL-1 receptor anatagonist, anti-TNFα/infliximab and sodium pentosan polysulfate/PPS) in two blocking-studies designed to determine how intervention timing influences drug efficacy. Cell viability, protein and gene expression for IL-1β, IL-6 & IL-8 were assessed. Results Timecourse: TNFα substantially increased the amount of IL-6, IL-8 & IL-1β, with IL-1β and IL-8 reaching equilibrium within ~72 hours (IL-1β: 111±40pg/mL, IL-8: 8478±957pg/mL), and IL-6 not reaching steady state after 144 hours (1570±435 pg/mL). Anti-TNFα treatment was most effective at reducing the expression of all cytokines measured when added at the same time as TNFα stimulation. Similar trends were observed when drugs were added 72 hours after TNFα stimulation, however, no anti-inflammatories significantly reduced cytokine levels compared to TNF control. Conclusion IL-1β, IL-6 and IL-8 were expressed at different rates and magnitudes suggesting different roles for these cytokines in disease

  2. Latent Herpes Viruses Reactivation in Astronauts

    Science.gov (United States)

    Mehta, Satish K.; Pierson, Duane L.

    2008-01-01

    Space flight has many adverse effects on human physiology. Changes in multiple systems, including the cardiovascular, musculoskeletal, neurovestibular, endocrine, and immune systems have occurred (12, 32, 38, 39). Alterations in drug pharmacokinetics and pharmacodynamics (12), nutritional needs (31), renal stone formation (40), and microbial flora (2) have also been reported. Evidence suggests that the magnitude of some changes may increase with time in space. A variety of changes in immunity have been reported during both short (.16 days) and long (>30 days) space missions. However, it is difficult to determine the medical significance of these immunological changes in astronauts. Astronauts are in excellent health and in superb physical condition. Illnesses in astronauts during space flight are not common, are generally mild, and rarely affect mission objectives. In an attempt to clarify this issue, we identified the latent herpes viruses as medically important indicators of the effects of space flight on immunity. This chapter demonstrates that space flight leads to asymptomatic reactivation of latent herpes viruses, and proposes that this results from marked changes in neuroendocrine function and immunity caused by the inherent stressfullness of human space flight. Astronauts experience uniquely stressful environments during space flight. Potential stressors include confinement in an unfamiliar, crowded environment, isolation, separation from family, anxiety, fear, sleep deprivation, psychosocial issues, physical exertion, noise, variable acceleration forces, increased radiation, and others. Many of these are intermittent and variable in duration and intensity, but variable gravity forces (including transitions from launch acceleration to microgravity and from microgravity to planetary gravity) and variable radiation levels are part of each mission and contribute to a stressful environment that cannot be duplicated on Earth. Radiation outside the Earth

  3. Relaxin has anti-apoptotic effects on human trophoblast-derived HTR-8/SV neo cells.

    Science.gov (United States)

    Lodhi, Romana S Z; Nakabayashi, Koji; Suzuki, Kaho; Yamada, Ai Y; Hazama, Rhoichi; Ebina, Yasuhiko; Yamada, Hideto

    2013-12-01

    The study was conducted to evaluate the effects of human relaxin on apoptosis in the human trophoblast derived HTR-8/SV neo cell line, which is a possible model of human extravillous trophoblasts (EVTs). HTR-8/SV neo cells, cultured in phenol red free RPMI1640 medium, were treated with different doses of human recombinant (rH2) relaxin in serum-deprived conditions. RT-PCR was used for evaluating relaxin receptor: RXFP1 and RXFP2 expression in HTR-8/SV neo cells. The cell death was examined by TUNEL assay. Furthermore, we investigated caspase-3, cleaved PARP and Bcl-2 expressions by Western blot analysis to recognize the translational effects of anti-apoptotic and pro-apoptotic proteins. RXFP1 and RXFP2 mRNA expression was observed in HTR-8/SV neo cells. Compared with untreated control cultures, treatment with rH2 relaxin, decreased TUNEL-positive rate in HTR-8/SV neo cells was observed. Western blot analysis revealed that treatment with rH2 relaxin decreased the expression of caspase-3 and cleaved PARP, but in contrast increased Bcl-2 expression in those cells. These results suggest that rH2 relaxin has anti-apoptotic effects on HTR8/SV neo cells by decreasing pro-apoptotic caspase-3 and cleaved PARP expression and up-regulating anti-apoptotic Bcl-2 expression. PMID:24070111

  4. Hypoxia attenuates anti-Aspergillus fumigatus immune responses initiated by human dendritic cells.

    Science.gov (United States)

    Fliesser, Mirjam; Wallstein, Marion; Kurzai, Oliver; Einsele, Hermann; Löffler, Jürgen

    2016-08-01

    Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that hypoxia at the site of A. fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients. PMID:27005862

  5. Targeted gene therapy of LS174 T human colon carcinoma by anti-TAG-72 immunoliposomes.

    Science.gov (United States)

    Kim, K S; Lee, Y K; Kim, J S; Koo, K H; Hong, H J; Park, Y S

    2008-05-01

    Anti-tumor-associated glycoprotein (TAG)-72 PEG-immunoliposomes (PILs) were prepared by conjugation of Fab' fragments of recombinant humanized monoclonal antibody, HuCC49, to sterically stabilize unilamellar liposomes (90-110 nm in diameter) to target TAG-72-overexpressing cancer cells. The liposomes consisted of 1-palmitonyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), 92 mol percent, O,O'-dymyrisyl-N-lysyl aspartate (DMKD cationic lipid), 4 mol percent, distearoyl-phosphatidyl-ethanolamine-polyethylene glycol 2000 (DSPE-PEG(2000)), 3 mol percent and DSPE-maleimide (DSPE-PEG(2000)-Mal), 1 mol percent. These anti-TAG-72 PILs were able to adhere to the surface of TAG-72-overexpressing LS174 T human colon cancer cells more effectively than conventional liposomes. Also, in vitro gene transfection of the LS174 T cells by the anti-TAG-72 PILs in the presence of a high concentration of fetal bovine serum (up to 60%) was greater than that by conventional cationic lipoplexes. Intravenously administered anti-TAG-72 PILs efficiently localized in the LS174 T tumor tissues, while the non-targeted conventional liposomes did not. Intravenous administration of the anti-TAG-72 PILs containing plasmids encoding antiangiogenic proteins, such as angiostatin K1/3, endostatin and saxatilin, significantly inhibited in vivo growth of LS174 T tumors and angiogenesis in the tumor tissues. These results demonstrated the potential of TAG-72-mediated targeting of immunoliposomes as a modality for systemic gene delivery to human colon cancer cells. PMID:18309354

  6. Cross-reactivity of anti-H pylori antibodies with membrane antigens of human erythrocytes

    Institute of Scientific and Technical Information of China (English)

    Feng-Hua Guo; Fan-Ling Meng; Jian-Zhong Zhang; Xiao-Mei Yan; Chun-Xiang Fan; Fei Zhao; Yuan Hu; Di Xiao; Xun Zeng; Mao-Jun Zhang; Li-Hua He

    2007-01-01

    AIM: To investigate whether anti-H pylori antibodies have cross-reaction with antigens of erythrocyte membrane.METHODS: Blood samples were collected from 14 volunteers (8 positive and 6 negative for H pylori detected by 13C-urea breath test) of the general population. Erythrocyte membrane proteins of the subjects were examined by Western blot using antiH pylori serum. The proteins related to the positive bands were identified by mass spectrum analysis.RESULTS: Anti-H pylori antibodies had cross-reaction with the proteins of about 50 kDa of erythrocyte membranes in all samples independent of H pylori infection. One protein in the positive band was identified as Chain S, the crystal structure of the cytoplasmic domain of human erythrocyte Band-3 protein.CONCLUSION: Anti-H pylori antibodies cross-react with some antigens of human erythrocyte membrane, which may provide a clue for the relationship between H pylori infection and vascular disorders.

  7. Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults

    NARCIS (Netherlands)

    Bodsworth, NJ; Boag, F; Burdge, D; Genereux, M; Borleffs, JCC; Evans, BA; Modai, J; Colebunders, R; Thomas, M; DeHertogh, D; Pacelli, L; Thomis, J; Knight, E.L.; McNulty, AM; Delaney, C; VanHove, D; Sacks, S; Gage, L; McLeod, A; DiazMitoma, F; Fong, J; MacFadden, D; Martel, A; Rachlis, A; Salit, [No Value; Shafran, S; Szabo, J; Toma, E; Deschenes, L; Gill, J; Lalonde, R; Kaufhold, R; Molina, JM; Dellamonica, P; Rozenbaum, W; Kolsters, FP; Meenhorst, PL; Danner, S; Sprenger, HG; EllisPegler, RB; Moragas, J; Moyle, G; Colman, J; Parnell, A; McLean, KA; Holmes, DA; Kitchen, C.M.R.; Linde, A; Dahl, H; Dwyer, D

    1997-01-01

    The clinical efficacy and safety of sorivudine as treatment for acute cutaneous tester in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study, A total of 125 patients with laboratory-confirmed tester rash present for less than or equa

  8. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    International Nuclear Information System (INIS)

    A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively

  9. Human anti-rhesus D IgG1 antibody produced in transgenic plants

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads; Nielsen, Leif Kofoed;

    2002-01-01

    antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent......Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... properties to CHO cell-produced anti-RhD antibody, indicating its potential usefulness in diagnostic and therapeutic programs....

  10. Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy

    OpenAIRE

    Cemazar, M; Parkins, C. S.; Holder, A L; Chaplin, D. J.; Tozer, G. M.; Sersa, G

    2001-01-01

    Recent studies have indicated that the antitumour effectiveness of electrochemotherapy, a combination of chemotherapeutic drugs with application of high voltage electric pulses applied to the tumour nodule (electroporation), result in a significant reduction in tumour blood flow and may therefore be mediated by an anti-vascular mechanism. The aim of this study was to evaluate the cytotoxicity of electroporation with bleomycin or cisplatin on cultured human microvascular endothelial cells (HME...

  11. Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities

    OpenAIRE

    Shah, Vishal; Doncel, Gustavo F.; Seyoum, Theodoros; Eaton, Kristin M.; Zalenskaya, Irina; Hagver, Rena; Azim, Abul; Gross, Richard

    2005-01-01

    The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by Candida bombicola and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal ...

  12. Human anti-plague monoclonal antibodies protect mice from Yersinia pestis in a bubonic plague model.

    Directory of Open Access Journals (Sweden)

    Xiaodong Xiao

    Full Text Available Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252 and two anti-V-specific human mAb (m253, m254 by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.

  13. Pretreatment of Human Cervicovaginal Mucus with Pluronic F127 Enhances Nanoparticle Penetration without Compromising Mucus Barrier Properties to Herpes Simplex Virus

    OpenAIRE

    Ensign, Laura M.; Lai, Samuel K.; Wang, Ying-Ying; Yang, Ming; Mert, Olcay; Hanes, Justin; Cone, Richard

    2014-01-01

    Mucosal drug delivery nanotechnologies are limited by the mucus barrier that protects nearly all epithelial surfaces not covered with skin. Most polymeric nanoparticles, including polystyrene nanoparticles (PS), strongly adhere to mucus, thereby limiting penetration and facilitating rapid clearance from the body. Here, we demonstrate that PS rapidly penetrate human cervicovaginal mucus (CVM), if the CVM has been pretreated with sufficient concentrations of Pluronic F127. Importantly, the diff...

  14. Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet.

    Science.gov (United States)

    You, Jeong Soon; Lee, Yun Ju; Kim, Kyoung Soo; Kim, Sung Hoon; Chang, Kyung Ja

    2014-03-01

    Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases.

  15. Herpes Simplex Virus-1 and Bell's Palsy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-05-01

    Full Text Available The association between herpes simplex virus-1 (HSV-1 infection and Bell palsy was determined in 47 children studied at Children's Hospital at Montefiore, Bronx, NY. Swabs of saliva and conjunctiva were taken for PCR testing.

  16. Neuropsychological Outcomes of Neonatal Herpes Encephalitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-10-01

    Full Text Available Neuropsychological outcome and the relation to neuroimaging findings are studied in a cohort of 9 children between 2.5 and 13 years of age with neonatal herpes encephalitis, examined at Karolinska University Hospital, Sweden.

  17. Nodular colloid degeneration over herpes zoster scars

    Directory of Open Access Journals (Sweden)

    Mittal R

    1996-01-01

    Full Text Available A rare case of nodular colloid degeneration is reported which presented clinically as plaques studded with soft yellow papules simulating adult colloid milia superimposed only on herpes zoster scars of right side of the face.

  18. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis.

    Science.gov (United States)

    Bermudez, Maria A; Sendon-Lago, Juan; Seoane, Samuel; Eiro, Noemi; Gonzalez, Francisco; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

    2016-08-01

    The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'ìn vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro-inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM-hUCESCs to determine mediating proteins. Results showed that administration of CM-hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. PMID:27381329

  19. Single cycle structure-based humanization of an anti-nerve growth factor therapeutic antibody.

    Directory of Open Access Journals (Sweden)

    Sonia Covaceuszach

    Full Text Available Most forms of chronic pain are inadequately treated by present therapeutic options. Compelling evidence has accumulated, demonstrating that Nerve Growth Factor (NGF is a key modulator of inflammatory and nociceptive responses, and is a promising target for the treatment of human pathologies linked to chronic and inflammatory pain. There is therefore a growing interest in the development of therapeutic molecules antagonising the NGF pathway and its nociceptor sensitization actions, among which function-blocking anti-NGF antibodies are particularly relevant candidates.In this respect, the rat anti-NGF αD11 monoclonal antibody (mAb is a potent antagonist, able to effectively antagonize rodent and human NGF in a variety of in vitro and in vivo systems. Here we show that mAb αD11 displays a significant analgesic effect in two different models of persistent pain in mice, with a remarkable long-lasting activity. In order to advance αD11 mAb towards its clinical application in man, anti-NGF αD11 mAb was humanized by applying a novel single cycle strategy based on the a priori experimental determination of the crystal and molecular structure of the parental Fragment antigen-binding (Fab. The humanized antibody (hum-αD11 was tested in vitro and in vivo, showing that the binding mode and the NGF neutralizing biological activities of the parental antibody are fully preserved, with even a significant affinity improvement. The results firmly establish hum-αD11 as a lead candidate for clinical applications in a therapeutic area with a severe unmet medical need. More generally, the single-cycle structure-based humanization method represents a considerable improvement over the standard humanization methods, which are intrinsically empirical and require several refinement cycles.

  20. Single Cycle Structure-Based Humanization of an Anti-Nerve Growth Factor Therapeutic Antibody

    Science.gov (United States)

    Covaceuszach, Sonia; Marinelli, Sara; Krastanova, Ivet; Ugolini, Gabriele; Pavone, Flaminia; Lamba, Doriano; Cattaneo, Antonino

    2012-01-01

    Most forms of chronic pain are inadequately treated by present therapeutic options. Compelling evidence has accumulated, demonstrating that Nerve Growth Factor (NGF) is a key modulator of inflammatory and nociceptive responses, and is a promising target for the treatment of human pathologies linked to chronic and inflammatory pain. There is therefore a growing interest in the development of therapeutic molecules antagonising the NGF pathway and its nociceptor sensitization actions, among which function-blocking anti-NGF antibodies are particularly relevant candidates. In this respect, the rat anti-NGF αD11 monoclonal antibody (mAb) is a potent antagonist, able to effectively antagonize rodent and human NGF in a variety of in vitro and in vivo systems. Here we show that mAb αD11 displays a significant analgesic effect in two different models of persistent pain in mice, with a remarkable long-lasting activity. In order to advance αD11 mAb towards its clinical application in man, anti-NGF αD11 mAb was humanized by applying a novel single cycle strategy based on the a priori experimental determination of the crystal and molecular structure of the parental Fragment antigen-binding (Fab). The humanized antibody (hum-αD11) was tested in vitro and in vivo, showing that the binding mode and the NGF neutralizing biological activities of the parental antibody are fully preserved, with even a significant affinity improvement. The results firmly establish hum-αD11 as a lead candidate for clinical applications in a therapeutic area with a severe unmet medical need. More generally, the single-cycle structure-based humanization method represents a considerable improvement over the standard humanization methods, which are intrinsically empirical and require several refinement cycles. PMID:22403636

  1. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells

    OpenAIRE

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by...

  2. Human anti-rhesus D IgG1 antibody produced in transgenic plants

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads Jonas Birkbak; Nielsen, Leif Kofoed;

    2002-01-01

    Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent...

  3. Normally Occurring Human Anti-GM1 Immunoglobulin M Antibodies and the Immune Response to Bacteria

    Science.gov (United States)

    Alaniz, María E.; Lardone, Ricardo D.; Yudowski, Silvia L.; Farace, María I.; Nores, Gustavo A.

    2004-01-01

    Anti-GM1 antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children <1 month of age but could be detected after 1 month of age. Although most of the children older than 6 months of age were positive, there were still a few negative children. The appearance of anti-GM1 IgM antibodies showed a perfect concordance with two well-characterized antibacterial antibodies, anti-Forssman and anti-blood group A, which indicates a similar origin. We also studied IgM reactivity with lipopolysaccharides (LPSs) from gram-negative bacteria isolated from stool samples from healthy babies and from Escherichia coli HB101 in serum from individuals of different ages. We found a positive reaction with both LPSs in all the children more than 1 month of age analyzed, even in those that were negative for anti-GM1 antibodies. Anti-GM1 IgM antibodies were purified from adult serum by affinity chromatography and tested for the ability to bind LPSs from different bacteria. This highly specific preparation showed reactivity only with LPS from a strain of Campylobacter jejuni isolated from a patient with diarrhea. We conclude that normally occurring IgM antibodies are generated after birth, probably during the immune defense against specific bacterial strains. PMID:15039337

  4. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    Directory of Open Access Journals (Sweden)

    Pauls Sandra

    2009-07-01

    Full Text Available Abstract Background Reactivation of human herpesvirus 6 (HHV-6 occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections.

  5. Primary effusion lymphoma associated with Human Herpes Virus-8 and Epstein Barr virus in an HIV-infected woman from Kampala, Uganda: a case report

    Directory of Open Access Journals (Sweden)

    Osuwat Lawrence O

    2011-02-01

    Full Text Available Abstract Introduction Primary effusion lymphoma is a recently recognized entity of AIDS related non-Hodgkin lymphomas. Despite Africa being greatly affected by the HIV/AIDS pandemic, an extensive MEDLINE/PubMed search failed to find any report of primary effusion lymphoma in sub-Saharan Africa. To our knowledge this is the first report of primary effusion lymphoma in sub-Saharan Africa. We report the clinical, cytomorphologic and immunohistochemical findings of a patient with primary effusion lymphoma. Case presentation A 70-year-old newly diagnosed HIV-positive Ugandan African woman presented with a three-month history of cough, fever, weight loss and drenching night sweats. Three weeks prior to admission she developed right sided chest pain and difficulty in breathing. On examination she had bilateral pleural effusions. Haematoxylin and eosin stained cytologic sections of the formalin-fixed paraffin-embedded cell block made from the pleural fluid were processed in the Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda. Immunohistochemistry was done at the Institute of Haematology and Oncology "L and A Seragnoli", Bologna University School of Medicine, Bologna, Italy, using alkaline phosphatase anti-alkaline phosphatase method. In situ hybridization was used for detection of Epstein-Barr virus. The tumor cells were CD45+, CD30+, CD38+, HHV-8 LANA-1+; but were negative for CD3-, CD20-, CD19-, and CD79a- and EBV RNA+ on in situ hybridization. CD138 and Ki-67 were not evaluable. Our patient tested HIV positive and her CD4 cell count was 127/μL. Conclusions A definitive diagnosis of primary effusion lymphoma rests on finding a proliferation of large immunoblastic, plasmacytoid and anaplastic cells; HHV-8 in the tumor cells, an immunophenotype that is CD45+, pan B-cell marker negative and lymphocyte activated marker positive. It is essential for clinicians and pathologists to have a high index of suspicion of

  6. Synthesis of heparan and chondroitin sulfate proteoglycans by human endothelial cells is differentially affected by herpes simplex virus type I (HSV-1)

    International Nuclear Information System (INIS)

    Effects of HSV-1 infection on proteoglycan (PG) synthesis by human EC were studied as a model of EC injury. Confluent cultures of early passage umbilical vein EC were infected with HSV-1 at multiplicities of infection (MOI) from 0.001 to 1.0. In uninfected cultures, over 90% of the total [35S]sulfate-labeled macromolecules were divided into two major peaks on ion-exchange chromatography. One contained heparan sulfate (HSPG) and the other chondroitin/dermatan sulfate (CS/DSPG) proteoglycan. HSV-1 infection produced a dose-dependent inhibition of total PG synthesis of up to 75%. There were widely divergent effects on individual PG species. Inhibition of CS/DSPG synthesis was much more marked than that of the HSPG. At a MOI of 1.0, CS/DSPG was present at 13% of control values, compared to 30% for HSPG. There was about one log difference in the dose of virus required to produce 50% inhibition of cell/matrix HSPG relative to CS/DSPG. HSV-1 did not inhibit the generation of an undersulfated HSPG, which contained shorter glycosaminoglycan chains than the predominant species. The authors conclude that HSV-1 infection of human EC produces complex differential effects on proteoglycan synthesis

  7. Induction of Murine Mucosal CCR5-Reactive Antibodies as an Anti-Human Immunodeficiency Virus Strategy

    Science.gov (United States)

    Barassi, C.; Soprana, E.; Pastori, C.; Longhi, R.; Buratti, E.; Lillo, F.; Marenzi, C.; Lazzarin, A.; Siccardi, A. G.; Lopalco, L.

    2005-01-01

    The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1β chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity. PMID:15890924

  8. Antioxidant and anti-lipid peroxidation activities of Tamarindus indica seed coat in human fibroblast cells.

    Science.gov (United States)

    Nakchat, Oranuch; Meksuriyen, Duangdeun; Pongsamart, Sunanta

    2014-02-01

    Antioxidant activity and total phenolic content of tamarind seed coat extracts (TSCEs) were compared between the two extracts using boiling-water (TSCE-W) and 70% ethanol (TSCE-E) for extraction. TSCE-W, consisting of the highest phenolic content, possessed 2,2-diphenyl-1 -picrylhydrazyl (DPPH) radical scavenging and anti-lipid peroxidation activities much higher than TSCE-E and Trolox. Additionally, both TSCEs also exhibited superoxide anion and hydrogen peroxide scavenging activities higher than Trolox and BHA. Anti-lipid peroxidation and cytotoxicity of TSCE-W were also studied in human foreskin fibroblast CCD-1064Sk cells. Cytotoxic effect was not observed when exposed to TSCE-W up to 1 mg/mL for 12-48 h. However, TSCE-W significantly attenuated lipid peroxidation in H202-damaged cells. HPLC analysis showed the presence of (+)-catechin, (-)-epicatechin, and procyanidin B2 in TSCE-W, which could be responsible for antioxidant and anti-lipid peroxidation activities. The results suggest that an inexpensive and simple boiling-water extraction of TSCE-W may provide a valuable natural antioxidant source having anti-lipid peroxidation for health food additives, nutraceuticals as well as cosmeceuticals.

  9. Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

    International Nuclear Information System (INIS)

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CIIL- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CIIL-12) to liver cancer cell HepG2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-ClIL-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

  10. 人单纯疱疹病毒BDNF转基因重组体的构建表达及活性检测%Constrution of Human Single Herpes Virus Carried BDNF Gene Vector and Its Bioactivity Evaluation

    Institute of Scientific and Technical Information of China (English)

    王盛兰; 但齐琴; 荣荣; 王廷华; 张云辉

    2012-01-01

    目的 构建人单纯疱疹病毒(HSV)脑源性神经营养因子(BDNF)转基因重组体(HSV-BDNF),转染大鼠皮质神经元后并检测其表达及生物活性.方法 用RT-PCR方法扩增人BDNF基因,克隆并构建HSV-BDNF转基因重组体.构建成功后将其转染培养大鼠皮质神经元,观察其对皮质神经元存活的影响;用ELISA、免疫组化检测皮质神经元中BDNF的表达水平.结果 成功构建了HSV-BDNF转基因重组体,皮质神经元转染HSV-BDNF后BDNF表达水平明显上调(P<0.05),且明显促进皮质神经元生长(P<0.05).结论 成功构建了HSV-BDNF,能有效转染大鼠皮质神经元并促进BDNF高表达,且具有生物活性.%Objective To construct the recombinant vector of human single herpes virus (HSV) carried brain derived neurotrophic factor (BDNF) gene. Methods BDNF gene was acquired from rat brain tissue by RT-PCR, then was cloned into plasmid, and enveloped by HSV. The recombinant was used to transfer cultured cortical neurons. The number and neurite length of neurons were quantified. The BDNF level and subcellular localization were detected by ELISA and immunohistochemistry. Results HSV carried BDNF gene recombinant has been successfully constructed. The recombinant showed the bioactivity on the growth of cortical neurons. BDNF level was increased significantly in BDNF transferred group. Conclusion HSV carried BDNF gene recombinant. With the bioactivity, has been successfully constructed. This could provide the vector for the treatment of BDNF under disease condition base on transferring gene technique.

  11. Anti-angiogenic action of plasma hyaluronan binding protein in human umbilical vein endothelial cells.

    Science.gov (United States)

    Jeon, Ji Won; Song, Hyun Seok; Moon, Eun-Joung; Park, Shi-Young; Son, Myung Jin; Jung, Seung Youn; Kim, Ji Tae; Nam, Do-Hyun; Choi-Miura, Nam-Ho; Kim, Kyu-Won; Kim, Yung-Jin

    2006-07-01

    The kringle domain is a triple loop structure present in angiostatin and endostatin. The disulfide bond-linked kringle architectures have been known to be essential for anti-angiogenic activity. Plasma hyaluronan binding protein (PHBP) is a novel serine protease which consists of three epidermal growth factor (EGF) domains, a kringle domain, and a serine protease domain. PHBP can be cleaved autocatalytically to generate activity and is highly expressed in the human blood and liver. To determine the anti-angiogenic activities of PHBP, we purified recombinant mouse PHBP from stable cell line overexpressing PHBP and used protein in vivo and in vitro angiogenesis assays. We found that recombinant PHBP inhibits not only angiogenesis in vivo in chorioallantoic membrane (CAM) assay but also the basic fibroblast growth factor (bFGF)-induced proliferation, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependant manner. Moreover, we found that the kringle domain of PHBP was essential for the anti-angiogenic action of PHBP by the deletion mutants. These findings unravel a new function of PHBP as an inhibitor of the proangiogenic phenotype of vascular endothelial cells and demonstrate that the kringle domain of PHBP might be a potent novel inhibitor of activated endothelial cells in vitro and in vivo. PMID:16773202

  12. Human synthetic lethal inference as potential anti-cancer target gene detection

    Directory of Open Access Journals (Sweden)

    Solé Ricard V

    2009-12-01

    Full Text Available Abstract Background Two genes are called synthetic lethal (SL if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since existent SL data is mainly restricted to yeast screenings, the road towards human SL candidates is limited to inference methods. Results In the present work, we use phylogenetic analysis and database manipulation (BioGRID for interactions, Ensembl and NCBI for homology, Gene Ontology for GO attributes in order to reconstruct the phylogenetically-inferred SL gene network for human. In addition, available data on cancer mutated genes (COSMIC and Cancer Gene Census databases as well as on existent approved drugs (DrugBank database supports our selection of cancer-therapy candidates. Conclusions Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology.

  13. 77 FR 9678 - Prospective Grant of Exclusive License: The Development of Human Anti-CD22 Monoclonal Antibodies...

    Science.gov (United States)

    2012-02-17

    ... disease such as lupus and Sjogren's syndrome. The specific antibodies covered by this technology are... Human Anti-CD22 Monoclonal Antibodies for the Treatment of Human Cancers and Autoimmune Disease AGENCY... Antibodies Specific for CD22'' , PCT Application PCT/US2009/124109 entitled ``Human and Improved...

  14. 77 FR 41792 - Prospective Grant of Co-Exclusive License: The Development of Human Anti-CD22 Monoclonal...

    Science.gov (United States)

    2012-07-16

    ... lymphoblastic leukemia, and autoimmune disease such as lupus and Sjogren's syndrome. The specific antibodies... of Human Anti-CD22 Monoclonal Antibodies for the Treatment of Human Cancers and Autoimmune Disease... Monoclonal Antibodies Specific for CD22'' , PCT Application PCT/ US2009/124109 entitled ``Human and...

  15. Effects of herpes simplex virus thymidine kinase/acyclovir system on growth of human pulmonary adenocarcinoma A549 cell line in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    HE Xiang-liang; HE Dong-hua; GUO Xian-jian; QIAN Gui-sheng; HUANG Gui-jun; CHEN Wei-zhong; LI Shu-ping

    2002-01-01

    Objective: To observe the effect of anciclovir (ACV) treatment on tumors induced by inoculation of TK gene-transfected human pulmonary adenocarcinoma A549 cells in nude mice. Methods: A recombinant plasmid containing TK gene was constructed and transfected into A549 cells by electroporation. The sensitivity of the transgenic cells (A549-TK) to ACV was examined by MTT assay in vitro and for in vivo observation, inoculation of A549-TK and A-549 cells into nude mice was separately performed to induce tumor growth, the response of which to ACV treatment was observed, and the tumor tissues were pathologically examined. Results: A recombinant plasmid containing TK gene was successfully constructed and transfected into A549 cells. The sensitivity of A549-TK cells to ACV was 43 times higher than that of A549 cells. The tumors induced by A549-TK cells showed no significant increase in size after ACV treatment (P>0. 05), and light microscopy revealed local tissue necrosis, karyoklasis, and nuclei disappearance. Conclusion: A549-TK cells acquires sensitivity to ACV both in vitro and in vivo, and ACV can inhibit the growth of tumors induced by A549-TK cell inoculation in nude mice.

  16. Myricetin is a novel inhibitor of human inosine 5'-monophosphate dehydrogenase with anti-leukemia activity.

    Science.gov (United States)

    Pan, Huiling; Hu, Qian; Wang, Jingyuan; Liu, Zehui; Wu, Dang; Lu, Weiqiang; Huang, Jin

    2016-09-01

    Human inosine 5'-monophosphate dehydrogenase (hIMPDH) is a rate-limiting enzyme in the de novo biosynthetic pathway of purine nucleotides, playing crucial roles in cellular proliferation, differentiation, and transformation. Dysregulation of hIMPDH expression and activity have been found in a variety of human cancers including leukemia. In this study, we found that myricetin, a naturally occurring phytochemical existed in berries, wine and tea, was a novel inhibitor of human type 1 and type 2 IMPDH (hIMPDH1/2) with IC50 values of 6.98 ± 0.22 μM and 4.10 ± 0.14 μM, respectively. Enzyme kinetic analysis using Lineweaver-Burk plot revealed that myricetin is a mix-type inhibitor for hIMPDH1/2. Differential scanning fluorimetry and molecular docking simulation data demonstrate that myricetin is capable of binding with hIMPDH1/2. Myricetin treatment exerts potent anti-proliferative and pro-apoptotic effects on K562 human leukemia cells in a dose-dependent manner. Importantly, cytotoxicity of myricetin on K562 cells were markedly attenuated by exogenous addition of guanosine, a salvage pathway of maintaining intracellular pool of guanine nucleotides. Taking together, these results indicate that natural product myricetin exhibits potent anti-leukemia activity by interfering with purine nucleotides biosynthetic pathway through the suppression of hIMPDH1/2 catalytic activity. PMID:27378425

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Anti-HBs antibody of normal human subjects predominantly binds 54 K and 60 K dalton HBs polypeptides.

    OpenAIRE

    Ono,Ryosaku; Koide, Norio; Nagashima,Hideo

    1986-01-01

    The structure of hepatitis B virus surface antigen (HBs) recognized by anti-HBs antibody was analyzed by western blotting using anti-HBs sera obtained from normal subjects, from rabbits immunized with purified HBs and commercially available goat serum. The HBs used had 7 components of 24 K, 27 K, 33 K, 36 K, 39 K, 43 K and 67-72 K daltons. Goat anti-HBs serum bound all of these components, while human and rabbit anti-HBs sera bound only two components (60 K and 54 K daltons), which were hardl...

  19. Unusual initial presentation of herpes simplex virus as inguinal lymphadenopathy.

    Science.gov (United States)

    Fleming, Sarah A; Strickler, John G

    2015-01-01

    Genital herpes simplex virus (HSV) infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  20. Unusual Initial Presentation of Herpes Simplex Virus as Inguinal Lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Sarah A. Fleming

    2015-01-01

    Full Text Available Genital herpes simplex virus (HSV infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

  1. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Yiju Hou

    2015-02-01

    Full Text Available Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells, we investigated the possible synergistic anti-cancer effects between ginseng extract Rg3 and cytarabine on acute myeloid leukemia cells. Results of this study demonstrate that Rg3 can enhance the anti-proliferation effect of cytarabine on hl60 cells and may decrease the dosage of cytarabine needed for acute myeloid leukemia treatment.

  2. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  3. The effect of polyamines on the binding of anti-DNA antibodies from patients with SLE and normal human subjects.

    Science.gov (United States)

    Wang, Xiao; Stearns, Nancy A; Li, Xingfu; Pisetsky, David S

    2014-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE). To elucidate specificity further, the effect of polyamines on the binding of anti-DNA antibodies from patients with lupus was tested by ELISA to calf thymus (CT) DNA; we also assessed the binding of plasmas of patients and normal human subjects (NHS) to Micrococcus luteus (MC) DNA. As these studies showed, spermine can dose-dependently inhibit SLE anti-DNA binding to CT DNA and can promote dissociation of preformed immune complexes. With MC DNA as antigen, spermine failed to inhibit the NHS anti-DNA binding. Studies using plasmas adsorbed to a CT DNA cellulose affinity indicated that SLE plasmas are mixtures of anti-DNA that differ in inhibition by spermine and binding to conserved and non-conserved determinants. Together, these studies demonstrate that spermine can influence the binding of anti-DNA autoantibodies and may contribute to the antigenicity of DNA.

  4. Interaction studies reveal specific recognition of an anti-inflammatory polyphosphorhydrazone dendrimer by human monocytes

    Science.gov (United States)

    Ledall, Jérémy; Fruchon, Séverine; Garzoni, Matteo; Pavan, Giovanni M.; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Blanzat, Muriel; Poupot, Rémy

    2015-10-01

    Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti-inflammatory properties leading to efficient therapeutic control of inflammatory diseases in animal models. These properties are mainly prompted through activation of monocytes. Here, we disclose new insights into the molecular mechanisms underlying the anti-inflammatory activation of human monocytes by ABP-capped PPH dendrimers. Following an interdisciplinary approach, we have characterized the physicochemical and biological behavior of the lead ABP dendrimer with model and cell membranes, and compared this experimental set of data to predictive computational modelling studies. The behavior of the ABP dendrimer was compared to the one of an isosteric analog dendrimer capped with twelve azabiscarboxylate (ABC) end groups instead of twelve ABP end groups. The ABC dendrimer displayed no biological activity on human monocytes, therefore it was considered as a negative control. In detail, we show that the ABP dendrimer can bind both non-specifically and specifically to the membrane of human monocytes. The specific binding leads to the internalization of the ABP dendrimer by human monocytes. On the contrary, the ABC dendrimer only interacts non-specifically with human monocytes and is not internalized. These data indicate that the bioactive ABP dendrimer is recognized by specific receptor(s) at the surface of human monocytes.Dendrimers are nano-materials with perfectly defined structure and size, and multivalency properties that confer substantial advantages for biomedical applications. Previous work has shown that phosphorus-based polyphosphorhydrazone (PPH) dendrimers capped with azabisphosphonate (ABP) end groups have immuno-modulatory and anti

  5. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    International Nuclear Information System (INIS)

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals

  6. POTENT INVITRO ANTI-HUMAN IMMUNODEFICIENCY VIRUS-1 ACTIVITY OF MODIFIED HUMAN SERUM ALBUMINS

    NARCIS (Netherlands)

    JANSEN, RW; MOLEMA, G; PAUWELS, R; SCHOLS, D; DECLERCQ, E; MEIJER, DKF

    1991-01-01

    A series of neoglycoproteins was synthesized by coupling of thiophosgene-activated p-aminophenyl derivatives [Biol. Cell. 47:95-110 (1983); J. Histochem. Cytochem. 32:1091-1094 (1984)] of various sugars to human serum albumin. The compounds were evaluated for their in vitro activity against human im

  7. Temporal Lobe Encephalitis Need not Always be Herpes Simplex Encephalitis: Think of Tuberculosis.

    Science.gov (United States)

    Madireddi, Jagadesh; Reddy, Gowtham; Stanley, Weena; Prabu, Mukhyaprana

    2016-05-01

    Historically, temporal lobe encephalitis is considered as a pathognomonic feature of Herpes simplex encephalitis. This rule may not always be true and we believe that clinicians should keep their differential open. We here report once such. Case of a 36-year-old Indian male who developed altered sensorium following a prodrome of headache and fever. Examination and imaging suggested Temporal Lobe Encephalitis (TLE). Herpes encephalitis was considered and he was started on anti-virals awaiting lumbar puncture reports. Cerebrospinal fluid (CSF) analysis for Herpes Polymerase Chain Reaction (PCR) turned out to be negative. Later, to our surprise PCR for tuberculosis (TB) was positive. CSF was 100% lymphocytic and Adenosine deaminase was 12. He was started on 5 drug anti-tuberculosis regimen following which he showed a significant clinical improvement. Given the prevalence of tuberculosis in the sub-continent, clinicians must be aware of this diagnostic possibility when a patient with TLE does not respond to anti-virals. Apart from disease specific therapy, multi-disciplinary approach involving speech therapy is warranted. An early aetiological characterization of TLE has both diagnostic and prognostic implications, failing which patient may succumb. PMID:27437274

  8. Herpes simples no serviço de estomatologia do Hospital São Lucas da PUCRS: estudo epidemiológico =Herpes simplex at stomatology division of Hospital São Lucas, PUCRS: epidemiological study

    Directory of Open Access Journals (Sweden)

    Stemmer, Ana Carolina et al.

    2005-01-01

    Full Text Available O presente estudo teve por objetivo investigar o perfil epidemiológico do herpes simples entre os pacientes do Serviço de Estomatologia do Hospital São Lucas da PUCRS. Foram analisados 167 prontuários dos quais 98 (58,68% tiveram diagnóstico de gengivoestomatite herpética primária e 69 (41,32% de herpes recorrente. As variáveis idade e sexo dos pacientes, sintomas da manifestação herpética, sítios anatômicos afetados, linfadenopatia e complicações, bem como tratamento empregado foram analisadas. Na gengivoestomatite herpética, 69,38% tinham entre 21 e 40 anos. O sexo feminino foi o mais acometido tanto pela doença primária quanto pela recorrente. Entre os sítios da cavidade bucal destacaram-se língua e gengiva para a doença primária, e o vermelhão dos lábios para a secundária. Os sintomas mais freqüentes da primoinfecção foram febre e dor, já nas lesões recorrentes, destacaram-se dor e ardência. Todos os pacientes exibiram linfadenopatia. Analgésicos e antitérmicos foram as principais drogas no tratamento da gengiovoestomatite herpética primária, enquanto, para o herpes recorrente, foram os anti-sépticos e antivirais.

  9. Antiviral activity of trappin-2 and elafin in vitro and in vivo against genital herpes.

    Science.gov (United States)

    Drannik, Anna G; Nag, Kakon; Sallenave, Jean-Michel; Rosenthal, Kenneth L

    2013-07-01

    Serine protease inhibitor elafin (E) and its precursor, trappin-2 (Tr), have been associated with mucosal resistance to HIV-1 infection. We recently showed that Tr/E are among principal anti-HIV-1 molecules in cervicovaginal lavage (CVL) fluid, that E is ∼130 times more potent than Tr against HIV-1, and that Tr/E inhibited HIV-1 attachment and transcytosis across human genital epithelial cells (ECs). Since herpes simplex virus 2 (HSV-2) is a major sexually transmitted infection and risk factor for HIV-1 infection and transmission, we assessed Tr/E contribution to defense against HSV-2. Our in vitro studies demonstrated that pretreatment of endometrial (HEC-1A) and endocervical (End1/E6E7) ECs with human Tr-expressing adenovirus (Ad/Tr) or recombinant Tr/E proteins before or after HSV-2 infection resulted in significantly reduced virus titers compared to those of controls. Interestingly, E was ∼7 times more potent against HSV-2 infection than Tr. Conversely, knockdown of endogenous Tr/E by small interfering RNA (siRNA) significantly increased HSV-2 replication in genital ECs. Recombinant Tr and E reduced viral attachment to genital ECs by acting indirectly on cells. Further, lower viral replication was associated with reduced secretion of proinflammatory interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) and decreased NF-κB nuclear translocation. Additionally, protected Ad/Tr-treated ECs demonstrated enhanced interferon regulatory factor 3 (IRF3) nuclear translocation and increased antiviral IFN-β in response to HSV-2. Lastly, in vivo studies of intravaginal HSV-2 infection in Tr-transgenic mice (Etg) showed that despite similar virus replication in the genital tract, Etg mice had reduced viral load and TNF-α in the central nervous system compared to controls. Collectively, this is the first experimental evidence highlighting anti-HSV-2 activity of Tr/E in female genital mucosa. PMID:23637403

  10. Biocompatibility of Solid-Dosage Forms of Anti-Human Immunodeficiency Virus Type 1 Microbicides with the Human Cervicovaginal Mucosa Modeled Ex Vivo▿

    OpenAIRE

    Trifonova, Radiana T.; Pasicznyk, Jenna-Malia; Fichorova, Raina N.

    2006-01-01

    Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal...

  11. Houttuynia cordata targets the beginning stage of herpes simplex virus infection.

    Directory of Open Access Journals (Sweden)

    Pei-Yun Hung

    Full Text Available Herpes simplex virus (HSV, a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata, a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.

  12. Anti-proliferative activity of hop-derived prenylflavonoids against human cancer cell lines.

    Science.gov (United States)

    Busch, Christian; Noor, Seema; Leischner, Christian; Burkard, Markus; Lauer, Ulrich M; Venturelli, Sascha

    2015-06-01

    Flavonoids form a substantial group of secondary plant metabolites that display several health-promoting effects. Therefore, prenylflavonoids, a subclass of flavonoids, have attracted increasing attention. Here, we investigated the possible anti-cancer potential of 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), two prenylflavonoids present in hops and beer and demonstrate an unexpectedly pronounced, dose-dependent reduction of cellular proliferation of human PC-3 prostate cancer and UO.31 renal carcinoma cells upon treatment. Based on these findings 6-PN and 8-PN are currently further clinically evaluated in detail. PMID:25925225

  13. Herpes simplex ulcerative esophagitis in healthy children

    Directory of Open Access Journals (Sweden)

    Abdulrahman A Al-Hussaini

    2011-01-01

    Full Text Available Herpes simplex virus is a common cause of ulcerative esophagitis in the immunocompromised or debilitated host. Despite a high prevalence of primary and recurrent Herpes simplex virus infection in the general population, Herpes simplex virus esophagitis (HSVE appears to be rare in the immunocompetent host. We report three cases of endoscopically-diagnosed HSVE in apparently immunocompetent children; the presentation was characterized by acute onset of fever, odynophagia, and dysphagia. In two cases, the diagnosis was confirmed histologically by identification of herpes viral inclusions and culture of the virus in the presence of inflammation. The third case was considered to have probable HSVE based on the presence of typical cold sore on his lip, typical endoscopic finding, histopathological evidence of inflammation in esophageal biopsies and positive serologic evidence of acute Herpes simplex virus infection. Two cases received an intravenous course of acyclovir and one had self-limited recovery. All three cases had normal immunological workup and excellent health on long-term follow-up.

  14. Zebrafish: modeling for herpes simplex virus infections.

    Science.gov (United States)

    Antoine, Thessicar Evadney; Jones, Kevin S; Dale, Rodney M; Shukla, Deepak; Tiwari, Vaibhav

    2014-02-01

    For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.

  15. Anti-rods/rings: a human model of drug-induced autoantibody generation

    Directory of Open Access Journals (Sweden)

    S. John eCalise

    2015-02-01

    Full Text Available In recent years, autoantibodies targeting subcellular structures described as the rods and rings pattern in HEp-2 ANA have been presented as a unique case of autoantibody generation. These rod and ring structures (RR are at least partially composed of inosine monophosphate dehydrogenase type 2 (IMPDH2, and their formation can be induced in vitro by several small-molecule inhibitors, including some IMPDH2 inhibitors. Autoantibodies targeting these relatively unknown structures have been almost exclusively observed in hepatitis C (HCV patients who have undergone treatment with pegylated interferon-α/ribavirin (IFN/RBV combination therapy. To date, anti-RR antibodies have not been found in treatment-naïve HCV patients or in patients from any other disease groups, with few reported exceptions. Here, we describe recent advances in characterizing the RR structure and the strong association between anti-RR antibody response and HCV patients treated with IFN/RBV, detailing why anti-RR can be considered a human model of drug-induced autoantibody generation.

  16. THE EUKARYOTIC EXPRESSION OF HUMAN PERFORIN PROTEIN AND THE ESTABLISHMENT OF HYBRIDOMAS PRODUCING ANTI-HUMAN PERFORIN PROTEIN

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To prepare the monoclonal antibody against human perforin(HP). Methods Recombinant eukaryotic expression plasmid pCDM8-HP was extracted and purified, and the BALB/C mice were immunized with the plasmid. The hybridomas producing anti-HP McAbs were established by using hybridoma technique, then the specificity of the McAbs was identified by using immunocytochemical technique and Western blot. Results Three hybridoma cell lines secreting McAbs against human perforin were established, and the three McAbs showed positive only with LAK cells containing human perforin protein, and showed negative with inactive human peripheral blood lymphocytes (PBLs). The subclasses of the three McAbs were determined as lgG2bK. Western blot results showed that the three McAbs recognized a specific band of LAK cell lysateds with molecular weight of 70.0Kd. Conclusion The three hybridoma cell lines secreting McAbs against human perforin were established and the secreted McAbs were specific.

  17. A preliminary study on the relationship of human herpes virus 6 infection and glioma%人疱疹病毒6型感染与神经胶质瘤关系的初步研究

    Institute of Scientific and Technical Information of China (English)

    隋锐; 张烨; 陈一; 朴浩哲

    2014-01-01

    目的 探讨人疱疹病毒6型(human herpesvirus-6,HHV-6)感染与神经胶质瘤的关系.方法 将辽宁省肿瘤医院神经外科2011年6月-2013年5月收治的神经胶质瘤患者45例纳入病例组,将同期该医院收治且已排除神经胶质瘤的脑外伤患者45例作为对照组.分别采用巢式聚合酶链式反应(nested polymerase chain reaction,Nested-PCR)法检测两组研究对象人病变脑组织样本中HHV-6序列;采用免疫组化染色法检测两组研究对象人病变脑组织样本中HHV-6抗原的表达.结果 病例组HHV-6 DNA阳性率为31.11%,对照组HHV-6 DNA阳性率为6.67% (x2=8.755,P=0.003).病例组HHV-6早期抗原p41表达阳性率为22.22%,对照组HHV-6早期抗原p41表达阳性率为0.00%(x2=11.250,P=0.001).病例组HHV-6 DNA阳性率、HHV-6抗原阳性率均高于对照组,组间差异有统计学意义(P<0.05).结论 神经胶质瘤患者和非神经胶质瘤脑外伤患者病变脑组织中HHV-6感染率有差异,据此推断HHV-6感染在神经胶质瘤的发生和发展过程中起到一定的作用.%Objective To study the relationship of human herpes virus-6 (HHV-6) infection and glioma.Methods A total of 45 neurosurgery glioma patients who admitted to Shenyang tumour hospital from June 2011 to May 2013 were included in the case group,while another 45 cases with traumatic brain injury glioma were enrolled in the control group.Nested-PCR was used to detect HHV-6 DNA,immunohistochemistry method was used to detect the expression of HHV-6 in two groups.Results The HHV-6 DNA positive rate was 31.11% (14/45) and 6.67% (3/45) in case group and control group,respectively.There was statistical difference between them(x2 =8.755,P =0.003).The positive rate of p41 was 22.22% (10/45)in case group,while no p41 antigen was checkout from control group,there was statistical difference between them (x2 =11.250,P =0.001).Conclusions HHV-6 infection play a part in the occurrence and development of glioma.

  18. [How I treat...recurrent labial herpes].

    Science.gov (United States)

    Nikkels, A F; Piérard, G E

    2008-11-01

    Recurrent oro-labial herpes is predominantly caused by the herpes simplex virus type 1. Following the primary infection, the virus remains in a latent stage in the trigeminal ganglion. After episodic reactivations, it is transported via the V1 or V2 axons to the lower or upper lip. Although no causal treatment exists, a series of therapeutic options are currently available. It now appears that recurrent oro-labial herpes can be treated with shorter treatment schedules with the currently available antiviral drugs. In these instances, similar clinical efficacy was obtained with increased compliance of the patient, and reduction in both the economical impact and the amount of drug intake. Newer treatment strategies are emerging including non medicated hydrocolloid dressings and combinations of a systemic antiviral drug with a topical corticosteroid. PMID:19112988

  19. Anti-cancer effects of Kochia scoparia fruit in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Hye-Yeon Han

    2014-01-01

    Full Text Available Background: The fruit of Kochia scoparia Scharder is widely used as a medicinal ingredient for the treatment of dysuria and skin diseases in China, Japan and Korea. Especially, K. scoparia had been used for breast masses and chest and flank pain. Objective: To investigate the anti-cancer effect of K. scoparia on breast cancer. Materials and Methods: We investigated the anti-cancer effects of K. scoparia, methanol extract (MEKS in vitro. We examined the effects of MEKS on the proliferation rate, cell cycle arrest, reactive oxygen species (ROS generation and activation of apoptosis-associated proteins in MDA-MB-231, human breast cancer cells. Results: MTT assay results demonstrated that MEKS decreased the proliferation rates of MDA-MB-231 cells in a dose-dependent manner with an IC 50 value of 36.2 μg/ml. MEKS at 25 μg/ml significantly increased the sub-G1 DNA contents of MDA-MB-231 cells to 44.7%, versus untreated cells. In addition, MEKS induced apoptosis by increasing the levels of apoptosis-associated proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose polymerase (PARP. Conclusion: These results suggest that MEKS inhibits cell proliferation and induces apoptosis in breast cancer cells and that MEKS may have potential chemotherapeutic value for the treatment of human breast cancer.

  20. Anti-metastatic mechanism of mountain cultivated wild ginseng in human cancer cell line

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    Jang SB

    2010-03-01

    Full Text Available Objective : Ginseng is one of most widely used herbal medicine. Ginseng showed anti-metastasis activities. However, its molecular mechanisms of action are unknown. So we want to report the wild ginseng repress which plays key roles in neoplastic epithelial-mesenchymal transition process. Methods : Treatment of the human colorectal carcinoma LOVO cells and human gastric carcinoma SNU601 cells with the increased concentrations of cultivated wild ginseng extracts resulted in a gradual decrease in the AXIN2 gene expression. Results : Metastasis-suppressor genes, maspin and nm23 was not affected by the treatment of ginseng extracts in LOVO cells. Moreover, the mountain cultivated wild ginseng or mountain wild ginseng are similar in their inhibitory effects on the expression of AXIN2 gene, but are substantially stronger than cultivated ginseng. Conclusion : We described the novel mechanism of wild ginseng-induced anti-metastasis activity by repressing the expression of AXIN2 gene that plays key roles in epithelial-mesenchymal transition process.

  1. Activation of Human Neutrophils by the Anti-Inflammatory Mediator Esenbeckia leiocarpa Leads to Atypical Apoptosis

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    Rafael de Liz

    2012-01-01

    Full Text Available Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses potential anti-inflammatory properties, its effect in neutrophils, key players in inflammation, has never been investigated. In this study, a crude hydroalcoholic extract (CHE was used to evaluate the potential toxic or agonistic effect of E. leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 μg/mL, CHE increased actin polymerization and cell signaling events, especially p38 MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by cytology and by flow cytometry and, although CHE increased the apoptotic rate (by cytology and increased annexin-V binding, it did not, unexpectedly, increase CD16 shedding. CHE increased the degradation of the cytoskeletal proteins gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic activity of CHE was reversed by a pan-caspase inhibitor but not by a p38 inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces apoptosis by a caspase-dependent and p38-independent mechanism in an atypical fashion based on its lack of effect on CD16 shedding and vimentin degradation. Since the resolution of inflammation occurs by elimination of apoptotic neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well with its anti-inflammatory properties, as previously reported.

  2. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

    International Nuclear Information System (INIS)

    Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

  3. Biocatalytically Oligomerized Epicatechin with Potent and Specific Anti-proliferative Activity for Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ramaswamy Nagarajan

    2008-11-01

    Full Text Available Catechins, naturally occurring flavonoids derived from wine and green tea, are known to exhibit multiple health benefits. Epigallocatechin gallate (EGCG is one of the most widely investigated catechins, but its efficacy in cancer therapy is still inconsistent and limited. The poor stability of EGCG has contributed to the disparity in the reported anti-cancer activity and other beneficial properties. Here we report an innovative enzymatic strategy for the oligomerization of catechins (specifically epicatechin that yields stable, water-soluble oligomerized epicatechins with enhanced and highly specific anti-proliferative activity for human breast cancer cells. This one-pot oxidative oligomerization is carried out in ambient conditions using Horseradish Peroxidase (HRP as a catalyst yielding water-soluble oligo(epicatechins. The oligomerized epicatechins obtained exhibit excellent growth inhibitory effects against human breast cancer cells with greater specificity towards growth-inhibiting cancer cells as opposed to normal cells, achieving a high therapeutic differential. Our studies indicate that water-soluble oligomeric epicatechins surpass EGCG in stability, selectivity and efficacy at lower doses.

  4. The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans

    DEFF Research Database (Denmark)

    Mackey, A L; Kjær, Michael; Dandanell, Sune;

    2007-01-01

    The consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) is widespread among athletes when faced with muscle soreness or injury, but the effects of NSAIDs on satellite cell activity in humans are unknown. To investigate this, 14 healthy male endurance athletes (mean peak oxygen consumption...... of anti-inflammatory drugs attenuates the exercise-induced increase in satellite cell number, supporting the role of the cyclooxygenase pathway in satellite cell activity....

  5. Anti-wrinkle effects of a tuna heart H2O fraction on Hs27 human fibroblasts

    OpenAIRE

    Kim, Young-Min; JUNG, HEE-JIN; CHOI, JAE-SUE; NAM, TAEK-JEONG

    2015-01-01

    With the increase in life expectancy, there is also growing interest in anti-aging treatments and technologies. The development of anti-aging functional drugs for the skin, and foods from natural sources, may offer solutions to this global matter. Aging involves structural, functional and biochemical changes that occur throughout cells and bodily tissues; the amount of hormones secreted from of all human organs, including the skin, decreases over time. Matrix metalloproteinase (MMP) genes (MM...

  6. Discovery of a novel dual fungal CYP51/human 5-lipoxygenase inhibitor: implications for anti-fungal therapy.

    Directory of Open Access Journals (Sweden)

    Eric K Hoobler

    Full Text Available We report the discovery of a novel dual inhibitor targeting fungal sterol 14α-demethylase (CYP51 or Erg11 and human 5-lipoxygenase (5-LOX with improved potency against 5-LOX due to its reduction of the iron center by its phenylenediamine core. A series of potent 5-LOX inhibitors containing a phenylenediamine core, were synthesized that exhibit nanomolar potency and >30-fold selectivity against the LOX paralogs, platelet-type 12-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity against ovine cyclooxygenase-1 and human cyclooxygnease-2. The phenylenediamine core was then translated into the structure of ketoconazole, a highly effective anti-fungal medication for seborrheic dermatitis, to generate a novel compound, ketaminazole. Ketaminazole was found to be a potent dual inhibitor against human 5-LOX (IC50 = 700 nM and CYP51 (IC50 = 43 nM in vitro. It was tested in whole blood and found to down-regulate LTB4 synthesis, displaying 45% inhibition at 10 µM. In addition, ketaminazole selectively inhibited yeast CYP51 relative to human CYP51 by 17-fold, which is greater selectivity than that of ketoconazole and could confer a therapeutic advantage. This novel dual anti-fungal/anti-inflammatory inhibitor could potentially have therapeutic uses against fungal infections that have an anti-inflammatory component.

  7. Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells

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    Ruilin Li

    2016-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is one of the most studied tumor-associated antigens for cancer immunotherapy. An engineered anti-HER-2 chimeric A21 antibody (chA21 is a chimeric antibody targeted to subdomain I of the HER2 extracellular domain. Here, we report the anti-tumor activity of the novel engineered monoclonal antibody humanized chA21 (HuA21 that targets HER2 on the basis of chA21, and we describe the underlying mechanisms. Our results reveal that HuA21 markedly inhibits the proliferation and migration of HER2-overexpressing breast cancer cells and causes enhanced antibody-dependent cell-mediated cytotoxicity potency against HER2-overexpressing tumor cells. In particular, HuA21, but not trastuzumab (Tra, markedly suppresses growth and enhances the internalization of the antibody in Tra-resistant BT-474 breast cancer cells. These characteristics are highly associated with the intrinsic ability of HuA21 to down-regulate HER2 activation and inhibit the extracellular signal-regulated kinase 1/2 (ERK1/2 and protein kinase B (Akt signaling pathways. Furthermore, the combination of HuA21 with Tra synergistically enhances the anti-tumor effects in vitro and in vivo and inhibits HER2 activation and the ERK1/2 and Akt signaling pathways. Altogether, our results suggest that HuA21 may represent a unique anti-HER2 antibody with potential as a therapeutic candidate alone or in combination with other anti-HER2 reagents in cancer therapy.

  8. Anti-Inflammatory Effects of Lactobacillus Rahmnosus and Bifidobacterium Breve on Cigarette Smoke Activated Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Esmaeil Mortaz

    Full Text Available Chronic obstructive pulmonary disease (COPD is a major global health problem with cigarette smoke (CS as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus and Befidobacterium breve (B. breve attenuate the development of 'allergic asthma' in animals but their effects in COPD are unknown.To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR activation.We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation.Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05 in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05. The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05.This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD.

  9. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse.

    Science.gov (United States)

    Vincent, Marie; Teppaz, Géraldine; Lajoie, Laurie; Solé, Véronique; Bessard, Anne; Maillasson, Mike; Loisel, Séverine; Béchard, David; Clémenceau, Béatrice; Thibault, Gilles; Garrigue-Antar, Laure; Jacques, Yannick; Quéméner, Agnès

    2014-01-01

    Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. PMID:25072059

  10. Biodistribution and human dosimetry of enantiomer-1 of the synthetic leucine analog anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid

    Energy Technology Data Exchange (ETDEWEB)

    Nye, Jonathon A., E-mail: jnye@emory.edu; Jarkas, Nashwa; Schuster, David M.; Savir-Baruch, Bital; Voll, Ronald J.; Camp, Vernon M.; Goodman, Mark M.

    2011-10-15

    Introduction: The enantiomerically enriched (ee=90%, enantiomer 1) synthetic amino acid (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (anti-2-[{sup 18}F]FACPC-1) accumulates in malignant cells by elevated transport through the sodium-independent system-L (leucine preferring) amino acid transporter. The purpose of this study was to evaluate in vivo uptake and single-dose toxicity of anti-2-[{sup 18}F]FACPC-1 in animals as well as the individual organ and whole-body dose in humans. Methods: A DU145 xenograft rodent model was used to measure anti-2-[{sup 18}F]FACPC-1 uptake at 15, 30 and 60 min post-injection. Animals were sacrificed and organs harvested to measure the percent injected activity per organ and to calculate residence time. Anti-2-[{sup 18}F]FACPC-1 toxicity was assessed using a single microdose (37-74 MBq/kg) in nonhuman primates. Their vital signs were monitored for 2 h post-injection for drug-related effects. Human biodistribution studies were collected by sequential whole-body PET/CT scans on six healthy volunteers (three male and three female) for 120 min following a single 247{+-}61 MBq bolus injection of anti-2-[{sup 18}F]FACPC-1. Estimates of radiation dose from anti-2-[{sup 18}F]FACPC-1 to the human body were calculated using recommendations of the MIRD committee and MIRDOSE 3.0 software. Results: High anti-2-[{sup 18}F]FACPC-1 residence time was observed in the pancreas of the rodent model compared to the human data. No abnormal treatment-related observations were made in the nonhuman primate toxicity studies. Human venous blood showed no metabolites of anti-2-[{sup 18}F]FACPC-1 in the first 60 min post-injection. All volunteers showed initially high uptake in the kidneys followed by a rapid washout phase. The estimated effective dose equivalent was 0.0196 mSv/MBq. Conclusion: Anti-2-[{sup 18}F]FACPC-1 showed low background uptake in the brain, thoracic and abdominal cavities of humans, suggesting a possible use for detecting

  11. Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed

    OpenAIRE

    Sawada-Hirai, Ritsuko; Jiang, Ivy; Wang, Fei; Sun, Shu Man; Nedellec, Rebecca; Ruther, Paul; Alvarez, Alejandro; Millis, Diane; Morrow, Phillip R.; Kang, Angray S

    2004-01-01

    Background Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model. Methods Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination w...

  12. Early Diagnosis of Herpes Simplex Encephalitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-06-01

    Full Text Available Records of 38 patients, 23 boys and 15 girls (ages 3 months to 16 years [42% ages 3-12 months], seen between 1990 and 1997 with proven herpes simplex encephalitis (HSE, were reviewed retrospectively to determine the diagnostic reliability of polymerase chain reaction (PCR results, in a study at the Neuropediatric Service, Hopital Saint Vincent de Paul, Paris, France.

  13. Risk Factors for Herpes Zoster Among Adults.

    Science.gov (United States)

    Marin, Mona; Harpaz, Rafael; Zhang, John; Wollan, Peter C; Bialek, Stephanie R; Yawn, Barbara P

    2016-09-01

    Background.  The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector. Methods.  We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age ≥50 years during 2010-2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview. Results.  We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose-response relationship was not noted. All associations indicated were statistically significant (P .1). Conclusions.  We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown. PMID:27382600

  14. Herpes Zoster and Post-Herpetic Neuralgia

    NARCIS (Netherlands)

    van Wijck, Albert J. M.; Wallace, Mark; Mekhail, Nagy; van Kleef, Maarten

    2011-01-01

    Herpes zoster infection is caused by a reactivation of the latent varicella zoster virus that causes chicken pox. It appears predominantly in older adults whose immunity for the virus has waned. The natural course of the disease is usually favorable, and the symptoms disappear spontaneously within a

  15. Antiviral drug resistance of herpes simplex virus

    NARCIS (Netherlands)

    Stranska, Ruzena

    2004-01-01

    Infections with herpes simplex virus (HSV) usually have an asymptomatic or benign course. However, severe infections do occur, particularly in HIV/AIDS patients or transplant recipients, and may be life-threatening unless adequate antiviral therapy is given. Since its introduction in the early 1980

  16. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Directory of Open Access Journals (Sweden)

    Lucia Cattaneo

    Full Text Available Rosemary (Rosmarinus officinalis L. has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed.

  17. Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Andreas F.R. Sommer

    2011-07-01

    Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

  18. Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity.

    Science.gov (United States)

    Jadoon, Saima; Karim, Sabiha; Bin Asad, Muhammad Hassham Hassan; Akram, Muhammad Rouf; Khan, Abida Kalsoom; Malik, Arif; Chen, Chunye; Murtaza, Ghulam

    2015-01-01

    The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed. PMID:26448818

  19. Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity

    Directory of Open Access Journals (Sweden)

    Saima Jadoon

    2015-01-01

    Full Text Available The exposure to ultraviolet radiations (UVR is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS, leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed.

  20. Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity.

    Science.gov (United States)

    Jadoon, Saima; Karim, Sabiha; Bin Asad, Muhammad Hassham Hassan; Akram, Muhammad Rouf; Khan, Abida Kalsoom; Malik, Arif; Chen, Chunye; Murtaza, Ghulam

    2015-01-01

    The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review article summarizes various in vivo antioxidant studies on herbal creams loaded with phyto-extracts. These formulations may serve as cosmeceuticals to protect skin against injurious effects of UVR. The botanicals studied for dermatologic use in cream form include Acacia nilotica, Benincasa hispida, Calendula officinalis, Camellia sinensis, Camellia sinensis, Nelumbo nucifera, Capparis decidua, Castanea sativa, Coffea arabica, Crocus sativus, Emblica officinalis Gaertn, Foeniculum vulgare, Hippophae rhamnoides, Lithospermum erythrorhizon, Malus domestica, Matricaria chamomilla L., Moringa oleifera, Morus alba, Ocimum basilicum, Oryza sativa, Polygonum minus, Punica granatum, Silybum marianum, Tagetes erecta Linn., Terminalia chebula, Trigonella foenum-graecum, and Vitis vinifera. The observed anti-aging effects of cream formulations could be an outcome of a coordinating action of multiple constituents. Of numerous botanicals, the phenolic acids and flavonoids appear effective against UVR-induced damage; however the evidence-based studies for their anti-aging effects are still needed.

  1. Anti-Proliferative Effect of Rosmarinus officinalis L. Extract on Human Melanoma A375 Cells.

    Science.gov (United States)

    Cattaneo, Lucia; Cicconi, Rosella; Mignogna, Giuseppina; Giorgi, Alessandra; Mattei, Maurizio; Graziani, Giulia; Ferracane, Rosalia; Grosso, Alessandro; Aducci, Patrizia; Schininà, M Eugenia; Marra, Mauro

    2015-01-01

    Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed. PMID:26176704

  2. Anti-cancer effect of rubropunctatin against human gastric carcinoma cells BGC-823.

    Science.gov (United States)

    Zheng, Yunquan; Xin, Yanwen; Shi, Xianai; Guo, Yanghao

    2010-11-01

    The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR) and its cytotoxic activities against human gastric adenocarcinoma BGC-823 cells were studied both in vitro and in vivo. Rubropunctatin inhibited the proliferation of BGC-823 cells with an inhibitory concentration (IC₅₀) of 12.57 μM, while it exhibited no significant toxicity to normal gastric epithelial cell GES-1 at the same concentration. Treatment of BGC-823 cells with rubropunctatin resulted in a dose- and time-dependent apoptosis, as validated by the increase in the percentage of cells in sub-G1 phase and phosphotidylserine externalization. The in vivo experimental data demonstrated that rubropunctatin could offer similar therapeutic benefits in comparison with the same dose of taxol. After five times of intravenous injection, tumor weight in BGC-823-bearing nude mice reduced 23.5% at the dose of 8 mg/kg and 37.7% at the dose of 32 mg/kg, respectively. The expressions of 30 genes related to induction of apoptosis were found up-regulated significantly. The two most expressed genes were tumor necrosis factor (TNF) and DNA-damage inducible transcript 3. TNF was considered as a major mediator of apoptosis induced by rubropunctatin. This is the first report describing the anti-proliferative effect of rubropunctatin and its apoptosis mechanism on BGC-823 cells. Rubropunctatin has potential to be developed as a new natural anti-cancer agent. PMID:20730532

  3. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H;

    2004-01-01

    were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging of the...... human anti-mouse IgG antibodies (HAMA), described to create false positive results, may be due to a crossreacting fraction of the polyclonal circulating antibodies against bovine IgG....

  4. Biodistribution and radioimmunoimage of iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts

    International Nuclear Information System (INIS)

    Objective: To investigate the biodistribution of Iodine-125 labeled anti-human ADAM15 polyclonal antibody in nude mice bearing human gastric carcinoma xenografts. Methods: The anti-human ADAM15 polyclonal antibody was labeled with I-125 using Chloramine-T method. The labeling efficiency and radiochemical purity of 125I-anti-ADAM15 antibody were measured. The SPECT planar imaging of nude mice bearing gastric carcinoma xenografts were performed at 1, 4, 8, 24, and 48 h post-injection and the biodistribution of 125I-anti-ADAM15 antibody was measured at 48 h after injection. Results: The labeling efficiency of 125I-anti-ADAM15 antibody was (75.16±9.43)% and its radiochemical purity was (99.44±0.21)% . Tumors could be cleanly visualized in SPECT planar images, and the radioactivity ratio of tumor to non-tumor tissue was 3.84±0.43 at 48 h post-injection. Conclusion: 125I-anti-ADAM15 antibody can target the gastric carcinoma in vivo, and provide good radioimmunoimages. (authors)

  5. Discourses of Roma Anti-Discrimination in Reports on Human Rights Violations

    Directory of Open Access Journals (Sweden)

    Chloë Delcour

    2015-09-01

    Full Text Available In an effort to understand the paradox between the expansion of inclusion projects for the Roma and their persisting exclusion, this article explores human rights practice in order to grasp the complexity of meanings of inclusion negotiated in this practice. In this way, we scrutinize whether there are limiting factors within the inclusionary discourse itself. Specifically, we analyze the discourse in transnational judicial, political and civil society actors’ reports on violations of human rights against Roma. A strong shared tendency to frame the violations in terms of discrimination can be discerned in the reports, demonstrating a dominant concept in the human rights discourse for Roma. However, a framing analysis of the underlying assumptions of this concept shows that not all three actors offer the same solutions for obtaining non-discrimination, which can partly explain the limited impact of the ostensibly strong and inclusive anti-discrimination discourse. In contrast, the actors do share a negative attribution of responsibility to the nation states, but the effectiveness of this shared discursive claim can be questioned. This article illustrates how inclusion discourses are actually quite complex to grasp and so it substantiates the need for greater critical understanding of such discourses in further research.

  6. Anti-Human Tissue Factor Antibody Ameliorated Intestinal Ischemia Reperfusion-Induced Acute Lung Injury in Human Tissue Factor Knock-In Mice

    Science.gov (United States)

    Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-01

    Background Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Methodology/Principal Findings Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. Conclusions This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies. PMID:18231608

  7. Anti-tumor efficacy of paclitaxel against human lung cancer xenografts.

    Science.gov (United States)

    Yamori, T; Sato, S; Chikazawa, H; Kadota, T

    1997-12-01

    We examined paclitaxel for anti-tumor activity against human lung cancer xenografts in nude mice and compared its efficacy with that of cisplatin, currently a key drug for lung cancer chemotherapy. Five non-small cell lung cancers (A549, NCI-H23, NCI-H226, NCI-H460 and NCI-H522) and 2 small cell lung cancers (DMS114 and DMS273) were chosen for this study, since these cell lines have been well characterized as regards in vitro and in vivo drug sensitivity. These cells were exposed to graded concentrations of paclitaxel (0.1 to 1000 nM) for 48 h. The 50% growth-inhibitory concentrations (GI50) for the cell lines ranged from 4 to 24 nM, which are much lower than the achievable peak plasma concentration of paclitaxel. In the in vivo study, 4 cell lines (A549, NCI-H23, NCI-H460, DMS-273) were grown as subcutaneous tumors xenografts in nude mice. Paclitaxel was given intravenously as consecutive daily injections for 5 days at the doses of 24 and 12 mg/kg/day. Against every xenograft, paclitaxel produced a statistically significant tumor growth inhibition compared to the saline control. Paclitaxel at 24 mg/kg/day was more effective than cisplatin at 3 mg/kg/day with the same dosing schedule as above, although the toxicity of paclitaxel was similar to or rather lower than that of cisplatin, in terms of body weight loss. In addition, paclitaxel showed potent activity against 2 other lung cancer xenografts (NCI-H226 and DMS114). Therefore, paclitaxel showed more effective, wider-spectrum anti-tumor activity than cisplatin in this panel of 6 lung cancer xenografts. These findings support the potential utility of paclitaxel in the treatment of human lung cancer. PMID:9473739

  8. Trimeresurus venom inhibition of anti-HPA-1a and anti-HPA-1b antibody binding to human platelets.

    Science.gov (United States)

    Wlodar, S J; Stone, D L; Sinor, L T

    1995-01-01

    A solid-phase red cell adherence assay was used to demonstrate the specific inhibitory effect of seven species of Trimeresurus snake venom on the binding of HPA-1a- and HPA-1b-specific platelet antibodies. Trimeresurus venom did not inhibit the binding of HLA-, HPA-3a-, HPA-3b-, HPA-4a-, HPA-5a-, and HPA-5b-specific platelet antibodies. Venom from other genera of snakes, including representatives from Agkistrodon, Ancistrodon, Bitis, Bothrops, Bungarus, Causus, Crotalus, Dendroaspis, Ecis, Micrurus, Naja, Notechis, Ophiophagus, Pseudechis, Sepedon (Hemachatus), and Vipera, all failed to specifically inhibit anti-HPA-1a and HPA-1b binding. These results may indicate that the component in Trimeresurus snake venom previously reported to bind to the platelet GPIIb-IIIa complex, inhibiting fibrinogen binding, binds close to the HPA-1a and HPA-1b epitopes.

  9. Fruit Polyphenols: A Review of Anti-inflammatory Effects in Humans.

    Science.gov (United States)

    Joseph, Shama V; Edirisinghe, Indika; Burton-Freeman, Britt M

    2016-01-01

    Underlying etiological factors in the development of obesity-related chronic diseases are long-term imbalances of oxidative and inflammatory stress leading to tissue dysfunction, damage, and ultimately failure. Poor dietary quality contributes significantly to the oxidative and inflammatory status of an individual. Conversely, various dietary approaches, including specific dietary factors can mitigate or prevent the occurrence of these risk-conferring imbalances brought about by modern lifestyle. Plant-derived polyphenolic compounds are well known for their antioxidant properties. Recent evidence indicates these compounds may confer anti-inflammatory and/or inflammatory response stabilizing activities, which would have important implications in health maintenance and disease risk reduction. Commonly consumed fruits, such as grapes, berries, and oranges/orange juice, contain polyphenolic compounds that have been studied for their effects on inflammation, but the nature and extent of their effects in humans remain unclear. Therefore, this article aims to provide a comprehensive overview of human clinical trials investigating the acute and chronic (feeding) effect of polyphenols from commonly consumed fruits or their derived products on inflammation. PMID:25616409

  10. ANTI-TUMOR ACTIVITY AND IMMUNE RESPONSES INDUCED BY HUMAN CANCER-ASSOCIATED MUCIN CORE PEPTIDE

    Institute of Scientific and Technical Information of China (English)

    Ma Yunguo; Yuan Mei; Fei Lihua; Li Li

    1998-01-01

    Objective: To investigate the immune responses induced by apomucin which is a mixture of mucin core peptide, in mice for elucidating the role of mucin core peptide in the modulation of cancers. Methods:Apomucin was isolated from human pancreatic cancer cell line SW1990. The mice were immunized with this apomucin (10μg/time×6) plus DETOX. Results: When immunized, all mice developed delayed-type hypersensitivity (DTH) after challenged with apomucin or synthetic peptide MUC-2 or MUC-3, while the mice immunized with apomucin alone did not develop DTH.No antibodies were detected by ELISA after immunization. When the spleen cells of vaccinated mice were cocultured with this apomucin (10-50μg/ml) and rhIL-2(50U/ml) in vitro, the proliferated lymphocytes showed cytotoxicity against human cancer cells, including colon cancer, gastric cancer, pancreatic cancer and leukemia as measured by Cr-51 release assay. Antibodies against MUC-2 and MUC-3 could block the cytotoxicity. Conclusion: It was identified that a vaccine combined of apomucin and immune adjuvant DETOX can induce cellular immune response and anti-tumor cytotoxicity in mice.

  11. Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

    LENUS (Irish Health Repository)

    Greene, C M

    2010-05-01

    alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

  12. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Science.gov (United States)

    Abdelmagid, Nada; Bereczky-Veress, Biborka; Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  13. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  14. Isolation of a nucleocapsid polypeptide of herpes simplex virus types 1 and 2 possessing immunologically type-specific and cross-reactive determinants.

    Science.gov (United States)

    Heilman, C J; Zweig, M; Stephenson, J R; Hampar, B

    1979-01-01

    A polypeptide (p40) of approximately 40,000 molecular weight was isolated from herpes simplex virus type 1 and 2 nucleocapsids by gel filtration and ion exchange chromatography. This protein appears to be the same as protein 22a described previously (Gibson and Roizman, J. Virol. 10:1044--1052, 1972). Competition immunoassays were developed by using purified p40 and antisera prepared in guinea pigs. The assays indicated that the p40's from herpes simplex virus types 1 and 2 possess both type-specific and cross-reactive antigenic determinants. Antibodies to the p40 cross-reactive determinant reacted with antigens in simian herpes virus SA8-infected cells, but not with antigens induced by pseudorabies virus. Preliminary results indicated that a radioimmunoprecipitation test can be used to detect type-specific herpes simplex virus p40 antibodies in human sera. PMID:85720

  15. Sensitive and simultaneous quantification of zinc pyrithione and climbazole deposition from anti-dandruff shampoos onto human scalp

    NARCIS (Netherlands)

    G. Chen; M. Miao; M. Hoptroff; X. Fei; L.Z. Collins; A. Jones; H.G. Janssen

    2015-01-01

    A sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and validated for simultaneous quantification of zinc pyrithione (ZPT) and climbazole (CBZ) deposited onto human scalp from anti-dandruff (AD) shampoos. Scrubbing with a buffer so

  16. Herpes zoster duplex bilateralis in an immunocompetent host

    Directory of Open Access Journals (Sweden)

    Pratik Gahalaut

    2012-01-01

    Full Text Available Varicella zoster virus causes both chicken pox and herpes zoster. The phenomenon of herpes zoster occurring concurrently in two non-contiguous dermatomes involving different halves of the body is termed herpes zoster duplex bilateralis (HZDB. Few cases, reported in the literature, were seen in either an immunosuppressed host or in the older age group. Here we present a case of HZDB in an immunocompetent host, probably the first in India.

  17. Herpes zoster duplex bilateralis in an immunocompetent host

    OpenAIRE

    Pratik Gahalaut; Sandhya Chauhan

    2012-01-01

    Varicella zoster virus causes both chicken pox and herpes zoster. The phenomenon of herpes zoster occurring concurrently in two non-contiguous dermatomes involving different halves of the body is termed herpes zoster duplex bilateralis (HZDB). Few cases, reported in the literature, were seen in either an immunosuppressed host or in the older age group. Here we present a case of HZDB in an immunocompetent host, probably the first in India.

  18. Herpes zoster duplex bilateralis in an immunocompetent host.

    Science.gov (United States)

    Gahalaut, Pratik; Chauhan, Sandhya

    2012-01-01

    Varicella zoster virus causes both chicken pox and herpes zoster. The phenomenon of herpes zoster occurring concurrently in two non-contiguous dermatomes involving different halves of the body is termed herpes zoster duplex bilateralis (HZDB). Few cases, reported in the literature, were seen in either an immunosuppressed host or in the older age group. Here we present a case of HZDB in an immunocompetent host, probably the first in India. PMID:23130258

  19. The role of NMDA receptors in human eating behavior: evidence from a case of anti-NMDA receptor encephalitis

    OpenAIRE

    Perogamvros, Lampros; Schnider, Armin; Leemann, Béatrice Anne Valérie

    2012-01-01

    Research in animal models has implicated N-methyl-D-aspartate (NMDA) receptors (NMDARs) in the control of food intake. Until now, these findings have been not replicated in humans. Here we describe a 22-year-old woman with anti-NMDAR encephalitis and no prior neurological or psychiatric history. Her clinical course was marked by successive eating disorders: anorexia followed by hyperphagia. We propose that, much as they do in other animals, NMDARs in humans interact with the neuroendocrine, h...

  20. Electrochemical biosensor for quantitation of anti-DNA autoantibodies in human serum.

    Science.gov (United States)

    Rubin, Robert L; Wall, David; Konstantinov, Konstantin N

    2014-01-15

    Measurement of serum autoantibody is a critical tool in the diagnosis and management of autoimmune diseases. However, rapid and convenient methods at the point-of care have not been achieved in large part because any one antibody species is a heterogeneous and miniscule fraction of the total serum immunoglobulin displaying identical properties other than its antigen-binding specificity. The present system addresses these challenges by vacuum-mediated transport of diluted serum through an antigen-coated porous membrane. To measure anti-DNA autoantibodies, native DNA was immobilized into a poly(vinylidene fluoride) membrane pre-coated with a synthetic phenylalanine/lysine co-polymer. Flow-through of primary and peroxidase-conjugated secondary antibodies over the course of 3 min enhanced productive antibody-antigen interactions by bringing the reactants into close mutual proximity. Signal was quantified electrochemically during the enzymatic conversion of the tetramethylbenzidine substrate to a charge-transfer complex. The electrochemical signals generated by sera from patients with systemic lupus erythematosus using this device showed good quantitative correlation with a standard enzyme-linked immunosorbent assay and displayed similar detection limits. Inter- and intra-assay variability and electrode uniformity were favorable as was a two-month test of the stability of the DNA-coated membrane. While refining the fluidics requirements of this biosensor will be needed, its capacity to quantify over the course of 30 min anti-DNA antibodies in fresh human serum without background reactivity of normal serum makes this a promising technology as a point-of care device of clinical utility.

  1. Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells

    Science.gov (United States)

    Muniyan, Sakthivel; D’Cunha, Napoleon; Robinson, Tashika; Hoelting, Kyle; Dwyer, Jennifer G.; Bu, Xiu R.; Batra, Surinder K.; Lin, Ming-Fong

    2015-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents. PMID:26121643

  2. Anti-tumor activity of CrTX in human lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    Bin YE; Yan XIE; Zheng-hong QIN; Jun-chao WU; Rong HAN; Jing-kang HE

    2011-01-01

    Aim:To assess the cytotoxic effect of crotoxin (CrTX),a potent neurotoxin extracted from the venom of the pit viper Crotalus durissus terrificus,in human lung adenocarcinoma A549 cells and investigated the underlying mechanisms.Methods:A549 cells were treated with gradient concentrations of CrTX,and the cell cycle and apoptosis were analyzed using a flow cytometric assay.The changes of cellular effectors p53,caspase-3 and cleaved caspase-3,total P38MAPK and pP38MAPK were investigated using Western blot assays.A549 xenograft model was used to examine the inhibition of CrTX on tumor growth in vivo.Results:Treatment of A549 cells with CrTX (25-200 μg/mL) for 48 h significantly inhibited the cell growth in a dose-dependent manner (IC50=78 μg/mL).Treatment with CrTX (25 iJg/mL) for 24 h caused G1 arrest and induced cell apoptosis.CrTX (25 μg/mL) significantly increased the expression of wt p53,cleaved caspase-3 and phospho-P38MAPK.Pretreatment with the specific P38MAPK inhibitor SB203580 (5 μmol/L) significantly reduced CrTX-induced apoptosis and cleaved caspase-3 level,but G1 arrest remained unchanged and highly expressed p53 sustained.Intraperitoneal injection of CrTX (10 μg/kg,twice a week for 4 weeks) significantly inhibited A549 tumor xenograft growth,and decreased MVD and VEGF levels.Conclusion:CrTX produced significant anti-tumor effects by inducing cell apoptosis probably due to activation of P38MAPK and caspase-3,and by cell cycle arrest mediated by increased wt p53 expression.In addition,CrTX displayed anti-angiogenic effects in vivo.

  3. Human teratomas express differentiated neural antigens. An immunohistochemical study with anti-neurofilament, anti-glial filament, and anti-myelin basic protein monoclonal antibodies.

    OpenAIRE

    Trojanowski, J Q.; Hickey, W. F.

    1984-01-01

    Monoclonal antibodies specific for neurofilament proteins, glial filament protein, or myelin basic protein were used with immunohistochemistry for evaluation of a series of 14 human benign and malignant teratomas for the presence of these neural specific antigens. The results indicate that human teratomas can express all of these neural antigens, reflecting the presence of differentiated neurons, astrocytes, and oligodendroglia, respectively. Although the tumors were selected because neural t...

  4. Paradigmenwechsel in der Anti-Aging-Medizin: Hormesis, Target-of-Rapamycin-Komplex und erste Anti-Aging-Pillen // Paradigm Shift in Anti-Aging Medicine: Hormesis, Target of Rapamycin Complex and First Human Anti-Aging-Pills

    Directory of Open Access Journals (Sweden)

    Römmler A

    2016-01-01

    Full Text Available Studies in model organisms have shown that some drugs and lifestyle practices (calorie-restricted diets, regular exercise, e.g. can extend life and health span and protect against the onset of age-related chronic diseases by targeting physiological pathways.brA common mode of action was found via mTOR (mechanistic Target Of Rapamycin pathway signalling. This intracellular protein kinase complex plays a key role in stimulating anabolic and cell growth promoting processes, while inhibiting autophagy. On the other hand, downregulation results in antiproliferative, anticancer and intensive cell-repairing effects leading to life and health span extension and stress resistance. The mTOR complex regulates such basic cell activities and integrates signals from nutrition sensing, energy metabolism, insulin and growth factors, stress and hypoxia.brImportantly, mTOR can be inhibited by some molecules and their analogs (rapamycin, resveratrol, metformin, e.g., which are released naturally from plants, yeast or bacteria to protect against natural enemies. Its dosage resembles an adaptive hormetic response relationship, as high concentrations are toxic and mild doses are associated with anticancer and antiaging effects. This opens up new avenues for their use as „anti-aging pills“ in humans.brRecent human data suggest that metformin, rapamycin and other mTOR-inhibitors could delay heart disease, cancer, cognitive decline and improve survival time in people with diabetes mellitus. In addition, response to influenca vaccine was enhanced by rapamycin in adults with immunosenescence, indicating beneficial anti-aging effects in the elderly.br“Treat aging” is an actual call to recognize aging as an indication appropriate for clinical trials and treatments, as it was recently approved by the Federal Drug Administration (FDA USA. p bKurzfassung/b: Die ansteigende Morbidität und Invalidität in alternden Industrienationen stößt an die Grenzen der Ressourcen

  5. Herpes zoster laryngitis accompanied by Ramsay Hunt syndrome.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Joo, Young Eun; Lim, Sang Chul

    2013-01-01

    The most common presentation of herpes zoster in the head and neck region is called Ramsay Hunt syndrome (RHS), which rarely accompanies multiple cranial neuropathy. Herpes zoster also involves the mucous membrane of the tongue, palate, pharynx, and larynx. Herpes zoster infection of the larynx accompanied by Ramsay Hunt syndrome with cranial polyneuropathy is extremely rare, with only few reported cases in the literature. At the time of this report, a review of the medical literature disclosed 4 reported cases of herpes zoster laryngitis accompanied by Ramsay Hunt syndrome. Herein, we present 2 additional cases and report the clinical outcome of cranial polyneuropathy with a review of the literature.

  6. Multiple antibody targets on herpes B glycoproteins B and D identified by screening sera of infected rhesus macaques with peptide microarrays.

    Directory of Open Access Journals (Sweden)

    Sven-Kevin Hotop

    Full Text Available Herpes B virus (or Herpesvirus simiae or Macacine herpesvirus 1 is endemic in many populations of macaques, both in the wild and in captivity. The virus elicits only mild clinical symptoms (if any in monkeys, but can be transmitted by various routes, most commonly via bites, to humans where it causes viral encephalitis with a high mortality rate. Hence, herpes B constitutes a considerable occupational hazard for animal caretakers, veterinarians and laboratory personnel. Efforts are therefore being made to reduce the risk of zoonotic infection and to improve prognosis after accidental exposure. Among the measures envisaged are serological surveillance of monkey colonies and specific diagnosis of herpes B zoonosis against a background of antibodies recognizing the closely related human herpes simplex virus (HSV. 422 pentadecapeptides covering, in an overlapping fashion, the entire amino acid sequences of herpes B proteins gB and gD were synthesized and immobilized on glass slides. Antibodies present in monkey sera that bind to subsets of the peptide collection were detected by microserological techniques. With 42 different rhesus macaque sera, 114 individual responses to 18 different antibody target regions (ATRs were recorded, 17 of which had not been described earlier. This finding may pave the way for a peptide-based, herpes B specific serological diagnostic test.

  7. Herpes zoster in the ulnar nerve distribution.

    Science.gov (United States)

    Athwal, G S; Bartsich, S A; Weiland, A J

    2005-08-01

    Varicella zoster is a ubiquitous virus which usually affects school-aged children as Chicken Pox. While the initial disease is self-limiting and seldom severe, the virus remains in the body. It lies dormant in the dorsal root ganglia and reactivation may occur years later with variable presentations as Herpes Zoster, or Shingles. While Shingles is common, it rarely presents exclusively in the upper extremity. It is important that hand surgeons recognize the possibility of zoster infection, with or without a rash, when evaluating the onset of neuralgia in a dermatomal distribution in the upper limb. Early diagnosis allows rapid and appropriate treatment, with a lower risk of complications. We report on a case of Herpes Zoster isolated to the ulnar nerve distribution in a young woman. PMID:15950335

  8. Decompressive craniectomy in herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Muhammed Jasim Abdul Jalal

    2015-01-01

    Full Text Available Intracranial hypertension is a common cause of morbidity in herpes simplex encephalitis (HSE. HSE is the most common form of acute viral encephalitis. Hereby we report a case of HSE in which decompressive craniectomy was performed to treat refractory intracranial hypertension. A 32-year-old male presented with headache, vomiting, fever, and focal seizures involving the right upper limb. Cerebrospinal fluid-meningoencephalitic profile was positive for herpes simplex. Magnetic resonance image of the brain showed swollen and edematous right temporal lobe with increased signal in gray matter and subcortical white matter with loss of gray, white differentiation in T2-weighted sequences. Decompressive craniectomy was performed in view of refractory intracranial hypertension. Decompressive surgery for HSE with refractory hypertension can positively affect patient survival, with good outcomes in terms of cognitive functions.

  9. Herpes zoster post-herpetic neuralgia.

    Science.gov (United States)

    Feller, L; Jadwat, Y; Bouckaert, M

    2005-11-01

    Post-herpetic neuralgia (PHN) is the most frequent complication of herpes zoster and often results in significant morbidity and a reduction in the patient's quality of life. The peripheral nerve injury that occurs during the acute phase of herpes zoster (HZ) leads to an abnormal tonic impulse discharge from primary nociceptive afferent neurons which induce slow temporal summation. This "wind-up" phenomenon is responsible for continuous partial depolarisation of second-order neurons with increased spontaneous impulse discharge and expanded receptive fields within the dorsal horn nociceptive neurons. The abnormal central processing involves the activation of N-methyl-D-aspartate (NMDA) receptors resulting in neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia which is typical of PHN. In addition, tonic input from non-nociceptive AB afferent neurons, maintained by sympathetic efferent activity, contribute to the development and maintenance of neuropathic pain in general, and a burning sensation in particular.

  10. HERPES ZOSTER KRURIS DEXTRA: LAPORAN KASUS

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    I Gede Agus Bhakti Suputra

    2014-09-01

    Full Text Available Herpes zoster adalah manifestasi klinis karena reaktivasi virus varisela zoster (VZV. Karakteristik penyakit ini ditandai dengan adanya ruam vesikular unilateral yang berkelompok dengan nyeri yang radikular sekitar dermatom. Dilaporkan kasus seorang laki-laki 45 tahun, diagnosis herpes zoster kruris dextra, gambaran klinis berupa vesikel bergerombol multipel, berbentuk bulat, dengan ukuran 0,3-0,5 cm diatas kulit eritematosus, unilateral, tidak menyilang garis tengah, umur vesikel dalam satu gerombolan sama, tetapi dengan gerombolan yang lain tidak sama, kulit diantara gerombolan normal. Pemeriksaan penunjang tes Tzank, hasilnya negatif dengan tidak ditemukannya sel giant multinukleat. Pengobatan diberikan asiklovir 5x800 mg per hari diminum secara oral selama 7 hari, bedak salisil 1% dan mentol 0,5 % dioleskan dua kali sehari pada lesi kering. Prognosis pasien baik.  

  11. Development history of herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Jia-wei WANG

    2014-08-01

    Full Text Available Herpes simplex encephalitis (HSE is an acute central nervous system infection caused by herpes simplex virus (HSV. Early clinical manifestations mainly include fever, headache and unconsciousness; when progressing, psychiatric symptoms can occur. Death or serious neurological sequelae will happen if not treated. With the development of laboratory tests and imaging techniques, the early diagnosis of HSE is possible. Even though imaging with temporal lobe abnormal signal has the implication to HSE, the application of polymerase chain reaction (PCR in detecting HSV DNA in cerebrospinal fluid is currently the "gold standard" to diagnose HSE. Once diagnosed, acyclovir must be given as soon as possible, as delayed treatment will result in a poor outcome. doi: 10.3969/j.issn.1672-6731.2014.08.003

  12. A tail-like assembly at the portal vertex in intact herpes simplex type-1 virions.

    Directory of Open Access Journals (Sweden)

    Michael F Schmid

    Full Text Available Herpes viruses are prevalent and well characterized human pathogens. Despite extensive study, much remains to be learned about the structure of the genome packaging and release machinery in the capsids of these large and complex double-stranded DNA viruses. However, such machinery is well characterized in tailed bacteriophage, which share a common evolutionary origin with herpesvirus. In tailed bacteriophage, the genome exits from the virus particle through a portal and is transferred into the host cell by a complex apparatus (i.e. the tail located at the portal vertex. Here we use electron cryo-tomography of human herpes simplex type-1 (HSV-1 virions to reveal a previously unsuspected feature at the portal vertex, which extends across the HSV-1 tegument layer to form a connection between the capsid and the viral membrane. The location of this assembly suggests that it plays a role in genome release into the nucleus and is also important for virion architecture.

  13. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  14. Human anti-rhinosporidial antibody does not cause metabolic inactivation or morphological damage in endospores of Rhinosporidium seeberi, in vitro

    Directory of Open Access Journals (Sweden)

    Arseculeratne S

    2005-01-01

    Full Text Available This report describes the use of the MTT-reduction and Evan′s blue-staining tests for the assessment of the viability and morphological integrity, respectively, of rhinosporidial endospores after exposure to sera from rhinosporidial patients with high titres of anti-rhinosporidial antibody. Sera from three patients, with nasal, ocular and disseminated rhinosporidiosis respectively were used, with human serum without anti-rhinosporidial antibody for comparison, with or without added fresh guinea pig serum as a source of complement. All four sera tested, with or without guinea-pig serum, had no effect on the morphological integrity or the viability of the endospores and it is suggested that anti-rhinosporidial antibody has no direct protective role against the endospores, the infective stage, in rhinosporidiosis. This finding is compatible with the occurrence of chronicity, recurrence and dissemination that are characteristic of rhinosporidiosis despite the presence of high titres of anti-rhinosporidial antibody in patients with these clinical characteristics. The possible occurrence of humoral mechanisms of immunity that involve anti-rhinosporidial antibody with cells such as leucocytes and NK cells, in vivo, cannot yet be discounted, although the presence of high titres of anti-rhinosporidial antibody in patients with chronic, recurrent and disseminated lesions might indicate that such antibody is non-protective in vivo.

  15. Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway.

    Science.gov (United States)

    Li, Qunyi; Wang, Yi; Zhang, Liudi; Chen, Lu; Du, Yongli; Ye, Ting; Shi, Xiaojin

    2016-06-01

    Naringenin (Nar), most abundant in oranges and tomatoes, are known for the hypocholesterolemic, anti-estrogenic, hypolipidemic, anti-hypertensive, and anti-inflammatory activities. Here, the present study was designed to investigate the in vitro and in vivo anti-angiogenesis of Nar. Inhibition of angiogenesis was determined in vitro by using proliferation, apoptosis, migration, and tube-formation assays in Nar-treated human endothelial cell. Finally, CAM assays were used to assess inhibitory effect of Nar on physiological angiogenesis in vivo. The data suggest that Nar should be a direct ERRα inhibitor capable of inhibiting angiogenesis in vitro and in vivo, including endothelial cell proliferation, survival, migration and capillary-like structures formation of HUVECs, as well as reduced neovascularization of the CAM. Furthermore, the effects exerted by Nar are cell cycle related and mediated by VEGF/KDR signaling pathway along with downregulation of certain proangiogenic inflammatory cytokines. Our data thus provide potential molecular mechanisms through which Nar manifests it as a promising anti-angiogenic and anti-cancer agent. PMID:27105956

  16. Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype

    Energy Technology Data Exchange (ETDEWEB)

    Mendlovic, S.; Brocke, S.; Meshorer, A.; Mozes, E. (Weizmann Institute of Science, Rehovot (Israel)); Shoenfeld, Y.; Bakimer, R. (Ben-Gurion Univ., Beer-Sheva (Israel)); Ben-Bassat, M. (Beilinson Medical Center, Petah-Tiqva (Israel))

    1988-04-01

    Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. The authors report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens (Sm, SS-A (Ro), and SS-B (La)), and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.

  17. Anti-HBs antibody of normal human subjects predominantly binds 54 K and 60 K dalton HBs polypeptides.

    Directory of Open Access Journals (Sweden)

    Ono,Ryosaku

    1986-06-01

    Full Text Available The structure of hepatitis B virus surface antigen (HBs recognized by anti-HBs antibody was analyzed by western blotting using anti-HBs sera obtained from normal subjects, from rabbits immunized with purified HBs and commercially available goat serum. The HBs used had 7 components of 24 K, 27 K, 33 K, 36 K, 39 K, 43 K and 67-72 K daltons. Goat anti-HBs serum bound all of these components, while human and rabbit anti-HBs sera bound only two components (60 K and 54 K daltons, which were hardly visible in the gel even by silver staining. Mixing the 24 K and 27 K components, and the 24 K and 43 K components without reducing reagent produced several polymerized forms of HBs components including 60 K and 54 K polypeptides, which were recognized by anti-HBs rabbit serum. Other combinations of HBs components did not yield any new polymeric forms. Thus, it was concluded that the formation of anti-HBs antibody in normal subjects might predominantly require an antigenic structure of polymeric forms of specific combinations of HBs polypeptides, other than previously known antigenic determinants.

  18. Measuring health-related quality of life in persons with genital herpes.

    Science.gov (United States)

    Wild, D; Patrick, D; Johnson, E; Berzon, R; Wald, A

    1995-12-01

    A disease-specific measure was needed for use in an international clinical trial to evaluate an investigational drug for genital herpes. A new measure was developed initially in the UK and translated and adapted for use in France, Italy, Germany, Denmark, Spain and the USA. This paper describes the translation and adaptation of the USA measure. It also describes the assessment of internal consistency, reproducibility, content validity, and construct validity (convergent and discriminant) of the measure. Two outcome measures of the final genital herpes-specific measure were developed: (1) a 21-item symptoms subscale; and (2) a 20-item HRQOL subscale. Each measure was scored and analyzed separately; the psychometric testing discussed in this paper refers to the HRQOL subscale only. The internal consistency of the HRQOL subscale is high (r = 0.93), as is the reproducibility measured with a two week interval (r = 0.85). Convergent validity is moderate to high. (Fleming Self-Regard subscale, r = 0.48; SF-36 Social Functioning dimension r = 0.59; SF-36 Mental Health dimension r = 0.50). The number of herpes outbreaks in the past year was a significant predictor of scores on the HRQOL subscale (0-1 outbreaks, mean = 82.1; 2+ outbreaks, mean = 72.1, p = 0.058) suggesting discriminant validity. The measure is currently in a phase III clinical trial including anti-viral therapy where the question of responsiveness can be addressed. PMID:8556013

  19. Herpes Simplex Viruses and Induction of Interferon Responses

    Institute of Scientific and Technical Information of China (English)

    Yijie Ma; Dustin Vepooten; Bin He

    2008-01-01

    Herpes simplex viruses (HSV) are human pathogens responsible for a variety of diseases,including localized mucocutaneous lesions,encephalitis,and disseminated diseases.HSV infection leads to rapid induction of innate immune responses.A critical part of this host response is the type I IFN system including the induction of type I IFNs,IFN-mediated signaling and amplification of IFN response.This provides the host with immediate countermeasure during acute infection to limit initial viral replication and to facilitate an appropriate adaptive immune response.However,HSV has devised multiple strategies to evade and interfere with innate immunity.This review will focus on the induction of type I IFN response by HSV during acute infection and current knowledge of mechanisms by which HSV interferes with this induction process.

  20. New strategies against drug resistance to herpes simplex virus

    Institute of Scientific and Technical Information of China (English)

    Yu-Chen Jiang; Hui Feng; Yu-Chun Lin; Xiu-Rong Guo

    2016-01-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV.

  1. New strategies against drug resistance to herpes simplex virus

    Science.gov (United States)

    Jiang, Yu-Chen; Feng, Hui; Lin, Yu-Chun; Guo, Xiu-Rong

    2016-01-01

    Herpes simplex virus (HSV), a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir (ACV) and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets (the DNA helicase/primase (H/P) complex), new types of molecules (nature products) and new antiviral mechanisms (lethal mutagenesis of Janus-type nucleosides) to fight the drug resistance of HSV. PMID:27025259

  2. The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections

    Directory of Open Access Journals (Sweden)

    Philipp Schuster

    2011-01-01

    Full Text Available In 1999, two independent groups identified plasmacytoid dendritic cells (PDC as major type I interferon- (IFN- producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a “spider web”, in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought.

  3. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    Science.gov (United States)

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  4. Herpes Zoster in a Healthy Child

    Directory of Open Access Journals (Sweden)

    Ahu Çiler Çıkım

    2009-12-01

    Full Text Available Varicella zoster virus (VZV is the causing agent of chickenpox which is common in children. Herpes zoster (HZ is a latent infection that is caused by VZV, which is localized in the cells of dorsal root ganglions. HZ is rare in childhood and is especially encountered in immunosuppressed children. Here, an immunocompetent child with HZ is presented and the clinical symptoms, treatment and complications of the infection are reviewed.

  5. Cytomegalovirus seropositivity is associated with herpes zoster

    OpenAIRE

    Ogunjimi, Benson; Hens, N; Pebody, R; H Jansens; H. Seale; Quinlivan, M.; Theeten, H.; Goossens, Herman; Breuer, Judy; Beutels, Philippe

    2015-01-01

    Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively r...

  6. Studying the Anti-aging Effect of Human Growth Hormone on Human Fibroblast Cells via Telomerase Activity

    Directory of Open Access Journals (Sweden)

    Nader Chaparzadeh

    2010-01-01

    Full Text Available Objective: In recent years, studies have focused on the telomerase for cancer treatmentby repressing telomerase in cancerous cells or prevent cell aging by activating it in theaged cells. Thus, in these studies natural and synthetic agents have been used to repressor activate telomerase. In this research, we investigated the effects of human growth hormone(hGH on aging via evaluation of telomerase activity.Materials and Methods: Primary human foreskin fibroblast cells were isolated, culturedand treated with different concentrations of hGH. BrdU and MTT cell proliferation assaysand cells number counting. Cell aging was assayed by the senescence sensitivegalactosidase staining method. Telomerase activity was measured with a telomerasePCR ELISA kit.Data were analyzed with SPSS software (one-way ANOVA and univariateANOVA.Results: Our results indicated that cells treated with a lower concentration (0.1, 1 ng/mlof hGH had more green color cells (aged cells. Furthermore, cell proliferation increasedwith increasing hGH concentrations (10 to 100 ng/ml which was significant in comparisonwith untreated control cells. TRAP assay results indicated that telomerase activityincreased with increasing hGH concentration, but there was no significant difference. Additionally,more rapid cell growth and telomerase activity was noted in the absence of H2O2when compared with the presence of H2O2, which was significantly different.Conclusion: Although increasing cell proliferation along with increasing hGH concentrationwas confirmed by all cell proliferation assays, only the cell counting test was statisticallysignificant. Thus, it is inconclusive that hGH (up to 100 ng/ml has an anti-agingeffect. Also, because there was no significant difference in the telomerase activity results(in spite of increasing progress along with increasing hGH concentration we can not certainlyconclude that hGH (up to 100 ng/ml impacts telomerase activity.

  7. Evaluation antiviral effect of leaf extract of Rosmarinus officinalis against Herpes simplex virus type 1 in cell cultur

    OpenAIRE

    G Yousefi Kordestani; M Parsania

    2015-01-01

    Introduction Herpes simplex virus type I belongs to herpesviridae. Several studies are ongoing for achieve a drug with good effectiveness and lower side effects, because the incidence of infections caused by this virus is increasing and there is some HSV resistance in the world. In this study, anti-viral effects of rosemary extract against of HSV was evaluated in cell culture. Material and methods: At first the rosemary extract toxicity on Hela cells with trypan blue and MTT methods has been ...

  8. Herpes zoster oticus: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Shailesh Gondivkar

    2010-01-01

    Full Text Available Herpes zoster oticus also known as Ramsay Hunt syndrome is a rare complication of herpes zoster in which reactivation of latent varicella zoster virus infection in the geniculate ganglion causes otalgia, auricular vesicles, and peripheral facial paralysis. Ramsay Hunt syndrome is rare in children and affects both sexes equally. Incidence and clinical severity increases when host immunity is compromised. Because these symptoms do not always present at the onset, this syndrome can be misdiagnosed. Although secondary to Bell′s palsy in terms of the cause of acute atraumatic peripheral facial paralysis, Ramsay Hunt syndrome, with incidence ranged from 0.3 to 18%, has a worse prognosis. Herpes zoster oticus accounts for about 12% cases of facial palsy, which is usually unilateral and complete and full recovery occurs in only about 20% of untreated patients. The most advisable method to treat Ramsay Hunt syndrome is the combination therapy with acyclovir and prednisone but still not promising, and several prerequisites are required for better results. We present a case of 32-year-old man suffering from Ramsay Hunt syndrome with grade V facial palsy treated effectively with rehabilitation program, after the termination of the combination therapy of acyclovir and prednisone.

  9. A REVIEW ARTICLE ON HERPES SIMPLEX ENCEPHALITIS

    Directory of Open Access Journals (Sweden)

    A. Karimi MD

    2009-01-01

    Full Text Available Abstract:Herpes Simplex encephalitis (HSE is a life threatening outcome of Herpes simplex virus (HSV infection of the central nervous system (CNS. HSVaccounts for 2-5 percent of all cases of encephalitis. One third of cases occur in those younger than 20 years old and one half in those older than 50 years old.Clinical diagnosis is recommended in the encephalopathic, febrile patients with focal neurological signs. However, the clinical findings are not pathogonomic because numerous other diseases of CNS can mimic HSE. Diagnosis should be confirmed based on medical history, analysis of cerebrospinal fluid (CSF for protein and glucose contents, the cellular analysis and identifying the pathogens by serology and Polymerase Chain Reaction (PCR amplification .The diagnostic gold standard is the detection of HSV DNA in the cerebrospinal fluid by PCR. But negative results need to be interpreted regarding thepatients clinical signs and symptoms and the time of CSF sampling. Spike and slow wave patterns is observed in Electroencephalogram (EEG.Neuroimaging, especially Magnetic Resonance Imaging (MRI is essential for evaluating the patients, which shows temporal lobe edema or hemorrhage.All patients with HSE should be treated by intravenous Acyclovir (10mg/kg q8hr for 14-21 days. After completing therapy, PCR of the CSF can confirmthe elimination of replicating virus, assisting further management of the patient.Keywords:Herpes Simplex Virus (HSV, Encephalitis, Children

  10. Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer

    International Nuclear Information System (INIS)

    Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC

  11. Herpes simplex virus interferes with amyloid precursor protein processing

    Directory of Open Access Journals (Sweden)

    Itzhaki Ruth F

    2005-08-01

    Full Text Available Abstract Background The early events underlying Alzheimer's disease (AD remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1 in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39–43 amino acid protein – β amyloid (Aβ – within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP. Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695 infected with the virus, using Western blotting. Results We have found that acute HSV1 (and also HSV2 infection rapidly reduces full length APP levels – as might be expected – yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide Conclusion Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD.

  12. Epidermodysplasia verruciformis with Hansen′s disease, herpes simplex labialis and multiple eccrine hidradenoma

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2009-01-01

    Full Text Available Epidermodysplasia verruciformis (EV - a rare, lifelong heritable disease due to a unique susceptibility to human papilloma virus. The disseminated verrucous lesions or pityriasis versicolor like lesions persist from early childhood and can transform into a cutaneous malignancy in a fourth of patients. The association of EV with multiple eccrine hidradenoma, herpes simplex labialis and Hansen′s disease is a very rare occurrence and is reported in a 25-year-old woman.

  13. Comparison of Cultureset and Bartels Immunodiagnostics with conventional tissue culture for isolation and identification of herpes simplex virus.

    OpenAIRE

    Sewell, D L; Horn, S A; Dilbeck, P W

    1984-01-01

    Two 48-h Vero cell systems were compared with viral culture in human fibroblastic cells for isolation and identification of herpes simplex virus from clinical specimens. Both 48-h systems had 79% sensitivity and greater than 99% specificity as compared with the conventional tissue culture method.

  14. Detection of varicella-zoster virus and herpes simplex virus by the polymerase chain reaction with degenerate primers

    NARCIS (Netherlands)

    Jacobs, J.J.L.; Folkers, E.; Vreeswijk, J.

    1999-01-01

    Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human pathogens of significance involved in multiple diseases with either typical or atypical clinical features. In neonates and immunocompromised patients these alphaherpesviruses may cause life-threatening diseases such as encephaliti

  15. Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

    Directory of Open Access Journals (Sweden)

    Yihan Hu

    2015-11-01

    Full Text Available A series of butylphthalide derivatives (BPDs 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae. The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5.

  16. "Anti-HBc alone" in human immunodeficiency virus-positive and immuno-suppressed lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    Yu Xuan Koo; Daniel SW Tan; Iain BH Tan; Richard Quek; Miriam Tao; Soon Thye Lim

    2009-01-01

    Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or "anti-HBc alone". In the context of immunodeficient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in "anti-HBc alone" patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.

  17. Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

    Science.gov (United States)

    Nash, A A; Gell, P G; Wildy, P

    1981-01-01

    Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed. PMID:7251047

  18. Coherent anti-Stokes Raman scattering microscopy of human smooth muscle cells in bioengineered tissue scaffolds

    Science.gov (United States)

    Brackmann, Christian; Esguerra, Maricris; Olausson, Daniel; Delbro, Dick; Krettek, Alexandra; Gatenholm, Paul; Enejder, Annika

    2011-02-01

    The integration of living, human smooth muscle cells in biosynthesized cellulose scaffolds was monitored by nonlinear microscopy toward contractile artificial blood vessels. Combined coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy was applied for studies of the cell interaction with the biopolymer network. CARS microscopy probing CH2-groups at 2845 cm-1 permitted three-dimensional imaging of the cells with high contrast for lipid-rich intracellular structures. SHG microscopy visualized the fibers of the cellulose scaffold, together with a small signal obtained from the cytoplasmic myosin of the muscle cells. From the overlay images we conclude a close interaction between cells and cellulose fibers. We followed the cell migration into the three-dimensional structure, illustrating that while the cells submerge into the scaffold they extrude filopodia on top of the surface. A comparison between compact and porous scaffolds reveals a migration depth of <10 μm for the former, whereas the porous type shows cells further submerged into the cellulose. Thus, the scaffold architecture determines the degree of cell integration. We conclude that the unique ability of nonlinear microscopy to visualize the three-dimensional composition of living, soft matter makes it an ideal instrument within tissue engineering.

  19. Anti-Proliferative Effect of Copper Oxide Nanorods Against Human Cervical Carcinoma Cells.

    Science.gov (United States)

    Pandurangan, Muthuraman; Nagajyothi, P C; Shim, Jaesool; Kim, Doo Hwan

    2016-09-01

    Metal oxide nanoparticles have been widely investigated for its use in the pharmacological field. The present study was aimed to investigate the cytotoxicity of copper oxide nanorods in human cervical carcinoma cells. The effect of copper oxide nanorods on cell viability was determined by sulforhodamine-B (SRB) assay. The fluorescence and confocal microscopy analyzes showed the cell rounding and nuclear fragmentation following exposure of copper oxide nanorods. Reactive oxygen species (ROS) was increased and could initiate membrane lipid peroxidation, which in turn regulate cytokinetic movements of cells. The messenger RNA (mRNA) expression of p53 and caspase 3 was increased, which further confirms the occurrence of apoptosis at the transcriptional level. Furthermore, caspase-3 enzyme activity was increased, which also confirms the occurrence of apoptosis in tumor cells at the translational level. Taking all our experimental results together, it may suggest that the copper oxide nanorods could be a potential anti-tumor agent to inhibit cancer cell proliferation. PMID:26811107

  20. Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization

    Science.gov (United States)

    Nesiel-Nuttman, Liron; Doron, Shani; Schwartz, Betty; Shoseyov, Oded

    2015-01-01

    Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin. Two selected peptides-A103-Q159 consisting of 57 amino acids and peptide K108-K133 consisting of 26 amino acids were demonstrated to have the highest actin binding ability and concomitantly the most potent anti-angiogenic activity. Further analyses on the putative mechanisms associated with angiogenesis inhibition exerted by peptide K108-K133 involved its location during treatment within the HUVE cells. Peptide K108-K133 readily penetrates the cell membrane within 10 min of incubation. In addition, supplementation with angiogenin delays the entrance of peptide K108-K133 to the cell suggesting competition on the same cell internalization route. The peptide was demonstrated to co-localize with angiogenin, suggesting that both molecules bind analogous cellular epitopes, similar to our previously reported data for ACTIBIND and trT2-50. PMID:25815360

  1. Effects of anti-human T lymphocyte immune globulins in patients: new or old.

    Science.gov (United States)

    Wang, Diane C; Wang, Xiangdong; Chen, Chengshui

    2016-09-01

    Multiple studies demonstrated that anti-human T lymphocyte immune globulins (ATG) can decrease the incidence of acute and chronic graft rejection in cell or organ transplants. However, further in-depth study indicates that different subgroups may benefit from either different regimes or alteration of them. Studies among renal transplant patients indicate that low immunological risk patients may not gain the same amount of benefit and thus tilt the risk versus benefit consideration. This may hold true for low immunological risk patients receiving other organ transplants and would be worth further investigation. The recovery time of T cells and natural killer (NK) cells also bears consideration and the impact that it has on the severity and incidence of opportunistic infections closely correlated with the dosage of ATG. The use of lower doses of ATG in combination with other induction medications may offer a solution. The finding that ATG may lose efficacy in cases of multiple transplants or re-transplants in the case of heart transplants may hold true for other transplantations. This may lead to reconsideration of which induction therapies would be most beneficial in the clinical setting. These studies on ATG done on different patient groups will naturally not be applicable to all, but the evidence accrued from them as a whole may offer us new and different perspectives on how to approach and potentially solve the clinical question of how to best reduce the mortality associated with chronic host-versus-graft disease. PMID:27084794

  2. Modulation of human malaria transmission by anti-gamete transmission blocking immunity.

    Science.gov (United States)

    de Zoysa, A P; Herath, P R; Abhayawardana, T A; Padmalal, U K; Mendis, K N

    1988-01-01

    Natural Plasmodium vivax malaria infections in man evoke anti-gamete transmission blocking antibodies which influence the infectivity of malaria patients to the vector mosquito. In this study, entomological, immunological and parasitological data obtained through the monitoring of an epidemic of human vivax malaria in Sri Lanka were used in a mathematical simulation to assess the effect of naturally induced transmission blocking immunity on malaria transmission. A mathematical model to describe malaria transmission accounting for transmission blocking immunity was developed from the basic differential equations originally stated by R. Ross and the epidemic was simulated using the available data. An attempt was made to predict the monthly malaria incidence by means of the mathematical simulation, with and without accounting for transmission blocking immunity. A plausible mathematical solution of the epidemic could be obtained when transmission blocking immunity was accounted for, and it was not possible to obtain such a plausible solution in the absence of immunity. Thus, the postulated occurrence of transmission blocking immunity was essential to describe adequately this malaria epidemic, indicating that, at least in epidemic situations, naturally occurring transmission blocking immunity has a controlling influence on malaria incidence. PMID:3076711

  3. Evaluation of anti-resistant activity of Auklandia(Saussurea lappa) root against some human pathogens

    Institute of Scientific and Technical Information of China (English)

    Sidgi Syed Anwer Hasson; Ali Abdullah Aljabri; Mohamed AhmedIdris; Mohammed Saeed Al-Balushi; KhazinaAlharthy; JumaZaidAl-Busaidi; MunaSulimanAldaihani; Mohammed Shafeeq Othman; Elias Antony Said; Omar Habal; Talal Abdullah Sallam

    2013-01-01

    Objective:The antimicrobial activity of the ethanol extract of the Auklandia (Saussurea lappa) root plant was investigated to verify its medicinal use in the treatment of microbial infections. Methods:The antimicrobial activity of the ethanol extract was tested against clinical isolates of some multidrug-resistant bacteria using the agar well diffusion method. Commercial antibiotics were used as positive reference standards to determine the sensitivity of the clinical isolates. Results:The extracts showed significant inhibitory activity against clinical isolates of methicillin resistant Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Extended Spectrum Beta-Lactemase, Acinetobacter baumannii. The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0 μg/μL-12.0 μg/μL. In the contrary the water extract showed no activity at all against the tested isolates. Furthermore, the results obtained by examining anti-resistant activity of the plant ethanolic extract showed that at higher concentration of the plant extract (12 μg) all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentration using the well diffusion assay. Conclusion:The results demonstrated that the crude ethanolic extract of the Auklandia (Saussurea lappa) root plant has a wide spectrum of activity suggesting that it may be useful in the treatment of infections caused by the above clinical isolates (human pathogens).

  4. Anti-inflammatory effects of antibacterials on human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Hatz Rudolf

    2009-09-01

    Full Text Available Abstract Background Human Bronchial epithelial cells (hu-BEC have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC. Methods Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l, azithromycin (AZM, 0.1-1.5 mg/l, levofloxacin (LVX, 1-8 mg/l and moxifloxacin (MXF, 1-16 mg/l. The spontaneous and TNF-α (10 ng/ml induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics. Results The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l by 37 ± 20% and 45 ± 31%, respectively (both p Conclusion Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-α induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.

  5. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1 that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication.

  6. Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma.

    Science.gov (United States)

    Kannan, Nagarajan; Kang, Jian; Kong, Xiangjun; Tang, Jianzhong; Perry, Jo K; Mohankumar, Kumarasamypet M; Miller, Lance D; Liu, Edison T; Mertani, Hichem C; Zhu, Tao; Grandison, Prudence M; Liu, Dong-Xu; Lobie, Peter E

    2010-12-01

    We report herein that trefoil factor 3 (TFF3) is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. Moreover, forced expression of TFF3 increased tumor size in xenograft models. Conversely, depletion of endogenous TFF3 with small interfering RNA (siRNA) decreased the oncogenicity and invasiveness of mammary carcinoma cells. Neutralization of secreted TFF3 by antibody promoted apoptosis, decreased cell growth in vitro, and arrested mammary carcinoma xenograft growth. TFF3 expression was significantly correlated to decreased survival of estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen. Forced expression of TFF3 in mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth, and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. siRNA-mediated depletion or antibody inhibition of TFF3 significantly enhanced the efficacy of antiestrogens. Increased TFF3 expression was observed in tamoxifen-resistant (TAMR) cells and antibody inhibition of TFF3 in TAMR cells improved tamoxifen sensitivity. Functional antagonism of TFF3 therefore warrants consideration as a novel therapeutic strategy for mammary carcinoma.

  7. Detection of anti-liver cell membrane antibody using a human hepatocellular carcinoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Lobo-Yeo, A.; McSorley, C.; McFarlane, B.M.; Mieli-Vergani, G.; Mowat, A.P.; Vergani, D.

    1989-02-01

    A radioimmunometric technique for the detection of autoantibodies to liver membrane antigens has been developed using Alexander cells, a human hepatocellular carcinoma cell line. After incubation of Alexander cells with serum, antimembrane antibodies were detected by addition of /sup 125/I-labeled Protein A. Binding ratios in 15 children with uncontrolled autoimmune chronic active hepatitis and in seven children with primary sclerosing cholangitis were significantly higher than in 18 age-matched normal controls. Nine patients with inactive autoimmune chronic active hepatitis, 13 with alpha 1-antitrypsin deficiency and five with fulminant hepatic failure had ratios similar to controls. In nine patients with Wilson's disease, there was a modest but significant increase in binding ratio. In four children with autoimmune chronic active hepatitis, binding ratios fell during effective immunosuppressive therapy. Sera from patients with systemic lupus erythematosus or rheumatoid arthritis gave normal results, excluding that binding derives from Fc-mediated immune complex capture. A positive correlation was found between Alexander cell binding values and anti-liver-specific protein antibody titers, suggesting that the two assays detect antibodies against shared antigenic determinants. The Alexander cell assay is a simple, rapid and sensitive technique to detect antibody to liver cell membrane antigens.

  8. Anti-proliferative effect of Ficus pumila Linn. on human leukemic cell lines

    Directory of Open Access Journals (Sweden)

    Christopher Larbie

    2015-04-01

    Conclusion: These findings suggest that crude extracts of FPS and FPL have anti-proliferative effect on the leukemia cells. The antioxidant properties of the plant including phenolics may be partly responsible for the anti-proliferative activity. Further studies are required to isolate chemical components of the plant and establish their anti-proliferative activities and mechanism of action. [Int J Basic Clin Pharmacol 2015; 4(2.000: 330-336

  9. Immunosuppressive Compounds Exhibit Particular Effects on Functional Properties of Human Anti-Aspergillus TH1 Cells

    OpenAIRE

    Tramsen, Lars; Schmidt, Stanislaw; Roeger, Frauke; Schubert, Ralf; Salzmann-Manrique, Emilia; Latgé, Jean-Paul; Klingebiel, Thomas; Lehrnbecher, Thomas

    2014-01-01

    Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk for invasive aspergillosis. Whereas adoptive immunotherapy transferring donor-derived anti-Aspergillus TH1 cells has been shown to be beneficial for HSCT recipients suffering from invasive aspergillosis, little is known about the impact of commonly used immunosuppressants on the functional properties of anti-Aspergillus TH1 cells. Anti-Aspergillus TH1 cells were coincubated with different concentrations of methyl...

  10. Cervical Antibodies to Herpes Simplex Virus Proteins in Pregnancy and Puerperium: A Pilot Study

    OpenAIRE

    D. Heather Watts; Jeanne-Marie Guise; Zane Brown; Lawrence Corey; Ashley, Rhoda L.

    1996-01-01

    Objective: This study was undertaken to evaluate the changes in total and anti-herpes simplex virus (HSV)-specific cervical IgA and IgG antibody profiles during and after pregnancy. Methods: Serum and cervical secretions were obtained from pregnant patients before 20 weeks gestation, at 34–36 weeks gestation, and at 6 weeks postpartum and tested for total IgA and IgG antibody and for IgA and IgG to HSV proteins by Western blot. Results: Seven women were HSV seronegative, 14 HSV-1 seropositive...

  11. Oriented immobilized anti-LDL antibody carrying poly(hydroxyethyl methacrylate) cryogel for cholesterol removal from human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Bereli, Nilay [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey); Sener, Guelsu [Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara (Turkey); Yavuz, Handan, E-mail: handany@hacettepe.edu.tr [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey); Denizli, Adil [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey)

    2011-07-20

    Low density lipoprotein (LDL) cholesterol is a major ingredient of the plaque that collects in the coronary arteries and causes coronary heart diseases. Among the methods used for the extracorporeal elimination of LDL from intravasal volume, immunoaffinity technique using anti-LDL antibody as a ligand offers superior selectivity and specificity. Proper orientation of the immobilized antibody is the main issue in immunoaffinity techniques. In this study, anti-human {beta}-lipoprotein antibody (anti-LDL antibody) molecules were immobilized and oriented through protein A onto poly(2-hydroxyethyl methacrylate) (PHEMA) cryogel in order to remove LDL from hypercholesterolemic human plasma. PHEMA cryogel was prepared by free radical polymerization initiated with N,N,N',N'-tetramethylene diamine (TEMED). PHEMA cryogel with a swelling degree of 8.89 g H{sub 2}O/g and 67% macro-porosity was characterized by swelling studies, scanning electron microscope (SEM) and blood compatibility tests. All the clotting times were increased when compared with control plasma. The maximum immobilized anti-LDL antibody amount was 63.2 mg/g in the case of random antibody immobilization and 19.6 mg/g in the case of oriented antibody immobilization (protein A loading was 57.0 mg/g). Random and oriented anti-LDL antibody immobilized PHEMA cryogels adsorbed 111 and 129 mg LDL/g cryogel from hypercholesterolemic human plasma, respectively. Up to 80% of the adsorbed LDL was desorbed. The adsorption-desorption cycle was repeated 6 times using the same cryogel. There was no significant loss of LDL adsorption capacity. - Research highlights: {yields} LDL cholesterol is a risk factor in the development of coronary heart diseases. {yields} Antibodies against LDL are used for the selective extracorporeal removal of LDL. {yields} Protein A is used for the oriented immobilization of anti LDL onto PHEMA cryogel. {yields} PHEMA cryogels are biocompatible, exhibit a low pressure drop, lack diffusion

  12. Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector.

    Science.gov (United States)

    Taylor, Travis J; Diaz, Fernando; Colgrove, Robert C; Bernard, Kristen A; DeLuca, Neal A; Whelan, Sean P J; Knipe, David M

    2016-09-01

    West Nile virus (WNV) is a flavivirus that swept rapidly across North America in 1999, declined in prevalence, and then resurged in 2012. To date, no vaccine is available to prevent infection in the human population. Herpes simplex virus (HSV) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and CD8(+) T cell responses even in HSV-immune animals. In this study, a WNV protein expression cassette was optimized for virus-like particle (VLP) production in transfection studies, and the cassette was recombined into an HSV-1 d106-WNV virus vector, which produced extracellular VLPs, as confirmed by immunoelectron microscopy. Immunization of mice with the d106-WNV recombinant vector elicited a specific anti-WNV IgG response. This study highlights the flavivirus coding sequences needed for efficient assembly of virus-like particles. This information will facilitate generation of additional vaccine vectors against other flaviviruses including the recently emerged Zika virus. PMID:27336950

  13. Monitoring of bystander effect of herpes simplex virus thymidine kinase/acyclovir system using fluorescence resonance energy transfer technique.

    Science.gov (United States)

    Xiong, Tao; Li, Yongjun; Ni, Fenge; Zhang, Feng

    2012-02-01

    Cytotoxic gene therapy mediated by gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by acyclovir (ACV) treatment has been reported to inhibit malignant tumor growth in a variety of studies. The magnitude of "bystander effect" is an essential factor for this anti-tumor approach in vivo. However, the mechanism by which HSV-tk/ACV brings "bystander effect" is poorly understood. In this report, the plasmid CD3 (ECFP-CRS-DsRed) and TK-GFP were transferred to the human adenoid cystic carcinoma line ACC-M cell line. The CD3-expressing cells apoptosis was monitored using fluorescence resonance energy transfer (FRET) technique. First, CD3 and TK-GFP co-expressing ACC-M cells apoptosis was monitored using FRET technique. The apoptosis was induced by ACV and initiated by caspase3. The FRET efficient was remarkably decreased and then disappeared during cellular apoptosis, which indicated that the TK-GFP expressing ACC-M cells apoptosis, induced by ACV, was via a caspase3-dependent pathway. Secondly, CD3 and TK-GFP mixed expressing ACC-M cells apoptosis, induced by ACV, were monitored using FRET technique. The apoptotic phenomena appeared in the CD3-expressing ACC-M cells. The results show that HSV-tk/ACV system killed ACC-M cells using its bystander effect. These results confirm that HSV-tk/ACV system is potential for cancer gene therapy.

  14. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan); Kameshima, Satoshi; Usui, Tatsuya; Okada, Muneyoshi; Hara, Yukio [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular

  15. Cross-reactivity of anti-human cytokine monoclonal antibodies used as a tool to identify novel immunological biomarkers in domestic ruminants.

    Science.gov (United States)

    Dorneles, E M S; Araújo, M S S; Teixeira-Carvalho, A; Martins-Filho, O A; Lage, A P

    2015-01-01

    Eleven commercially available PE-labeled anti-human (IL-1-α, IL-6, IL-8, TNF-α, IL-17A, IL-5, IL-10, IL-12 and IL-13) and anti-mouse (IL-10, TNF-α) cytokine monoclonal antibodies (mAbs) were tested for cross-reactivity with cattle, goat, and sheep cytokines. Cross-reactivity was assessed by comparative analysis with the standard reactivity of the target species. Our data demonstrated that anti-human IL-1-α, IL-6, IL-8, IL-17A and IL-10 mAbs cross-react with all ruminant species tested. Anti-human IL-5 mAb showed a strong cross-reactivity with cattle and goat IL-5, while anti-human TNF-α mAb showed a selective cross-reactivity with goat TNF-α. No cross-reactivity with the ruminant cytokines was observed for anti-human IL-12 and IL-13 mAbs or for the two anti-mouse cytokine mAbs tested. The present study demonstrated the cross-reactivity of various anti-human cytokine mAbs with cattle, sheep, and goat cytokines, increasing the range of immunological biomarkers for studies in veterinary medicine. PMID:25730032

  16. A simple method for assessment of human anti-Neu5Gc antibodies applied to Kawasaki disease.

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    Vered Padler-Karavani

    Full Text Available N-glycolylneuraminic acid (Neu5Gc is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. Anti-Neu5Gc antibodies are detected in all human sera, though with variable levels and epitope-recognition profiles. These antibodies likely play a role in several inflammation-mediated pathologies including cardiovascular diseases and cancer. In cancer, they have dualistic and opposing roles, either stimulating or repressing disease, as a function of their dose, and some of these antibodies serve as carcinoma biomarkers. Thus, anti-Neu5Gc antibodies may signify risk of inflammation-mediated diseases, and changes in their levels could potentially be used to monitor disease progression and/or response to therapy. Currently, it is difficult to determine levels of anti-Neu5Gc antibodies in individual human samples because these antibodies recognize multiple Neu5Gc-epitopes. Here we describe a simple and specific method for detection and overall estimation of human anti-Neu5Gc antibodies. We exploit the difference between two mouse models that differ only by Neu5Gc-presence (wild-type or Neu5Gc-absence (Cmah(-/- knockout. We characterize mouse serum from both strains by HPLC, lectin and mass-spectrometry analysis and show the target Neu5Gc-epitopes. We then use Cmah(-/- knockout sera to inhibit all non-Neu5Gc-reactivity followed by binding to wild-type sera to detect overall anti-Neu5Gc response in a single assay. We applied this methodology to characterize and quantify anti-Neu5Gc IgG and IgA in sera of patients with Kawasaki disease (KD at various stages compared to controls. KD is an acute childhood febrile disease characterized by inflammation of coronary arteries that untreated may lead to coronary artery aneurysms with risk of thrombosis and myocardial infarction. This estimated response is comparable to the average of detailed anti-Neu5Gc IgG profile analyzed by a sialoglycan microarray

  17. Clinical and morphological characteristics of herpes zoster in south India

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    Dubey Anand

    2005-01-01

    Full Text Available One hundred and seven cases (6 children and 101 adults of herpes zoster were recruited over a period of two years. The frequency of herpes zoster amongst skin OPD cases was found to be 0.34 per cent. The male to female ratio was 1.74:1. The most common prodromal symptom seen was paresthesia in 25 (23.36% cases followed by itching in 21 (19.62% cases.Most common presenting complaint was pain in 97 (90.65% cases. Ninety nine cases had classical herpes zoster followed by necrotic / ulcerated herpes zoster in 5 cases and hemorrhagic herpes zoster in 3 cases. Thoracic dermatome was the most common dermatome involved in 64 (59.8% cases followed by cervical in 17 (15.8% cases. Unidermatomal involvement was seen in 81 (75.7% cases, followed by multidermatomal in 18 (16.8% cases and disseminated in 8 (7.4% cases. Forty six cases were screened for HIV, out of them; six cases (4 males, 2 females were seropositive for HIV. Classical herpes zoster was a feature in four cases; however, one case each also had necrotic and hemorrhagic form of herpes zoster. To conclude, herpes zoster commonly occurs in young adults in India with presenting symptoms such as pain, itching and fever.

  18. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  19. Long-term observation of herpes simplex virus type 1 (HSV-1) infection in a child with Wiskott-Aldrich syndrome and a possible reactivation mechanism for thymidine kinase-negative HSV-1 in humans.

    Science.gov (United States)

    Shiota, Tomoyuki; Kurane, Ichiro; Morikawa, Shigeru; Saijo, Masayuki

    2011-01-01

    Herpes simplex virus type 1 (HSV-1) infections in a child with congenital immunodeficiency syndrome were observed over a 10-year period. The child suffered from recurrent and severe HSV-1 mucocutaneous infections. He frequently suffered from acyclovir (ACV)-resistant (ACV(r)) HSV-1 infection in the later phase of his life, especially after the episode of ACV(r) HSV-1 infection. Virological analyses on the HSV-1 isolates recovered from this patient revealed that all the ACV(r) HSV-1 isolates were thymidine kinase (TK)-negative (TK(-)) due to a single cytosine (C) deletion within the 4-C residues (positions 1061 to 1064) in the TK gene, indicating that the recurrent TK(-)/ACV(r) HSV-1 infections throughout the patient's life were due to the identical ACV(r) HSV-1 strain. Furthermore, it was found that the ACV-sensitive (ACV(s)) isolate recovered from the skin lesions that appeared between the episodes of ACV(r) infection at the ages of 8 and 9 contained ACV(r) HSV-1 with the same mutation in the TK gene. These results indicate that, although TK activity is required for reactivation of TK(+)/ACV(s) HSV-1 from latency and TK(-)/ACV(r) HSV-1 is unable to reactivate from latency, the TK(-)/ACV(r) HSV-1 strain isolated herein reactivated in this patient, possibly by using the TK activity induced by the latently co-infected TK(+)/ACV(s) HSV-1.

  20. Herpes simplex virus type 2: Seroprevalence in antenatal women

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    Rathore Shagufta

    2010-01-01

    Full Text Available Aims: To determine the seroprevalence of herpes simplex type 2 (HSV-2 infection in pregnant females, assess the frequency of unrecognized infection and identify the demographic profile and risk factors associated with the seroprevalence. Materials and Methods: Two hundred randomly selected, asymptomatic pregnant females attending the Obstetrics and Gynecology Outpatient Department for a routine antenatal check-up constituted the study group. Serum specimens were screened for HSV-2 infection by detecting IgG class antibodies against HSV-2-specific glycoprotein G-2 using an enzyme-linked immunosorbent assay kit. Results: A seroprevalence of 7.5% was found in our study. Seropositivity was maximum in the age group ≥30 years (22.20%, followed by 26-30 years (9.7%, 21-25 years (2.20% and ≤20 years (0%. HSV-2 seropositivity was found to be significantly associated with increasing age, parity, number of sexual partners, duration of sexual activity and history of abortions (P < 0.05. No statistically significant correlation was observed between seropositivity and other demographic variables such as place of residence, education, annual family income and occupation (P > 0.05. No statistically significant association of seropositivity with present or past history suggestive of other sexually transmitted infections was found. None of our cases tested positive for human immunodeficiency syndrome (HIV. Conclusion: A relatively low prevalence of HSV-2 seropositivity was found in our study, with a high frequency of unrecognized and asymptomatic infections. Our findings suggest that type-specific serotesting could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections and, therefore, to reduce the risk of HSV-2 and HIV sexual transmission by prophylactic counseling against unprotected intercourse. It may also be a useful adjunct in detecting cases who present with symptoms not directly suggestive of genital herpes.

  1. Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus

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    Koji Toriyama

    2014-10-01

    Full Text Available Background: We report a case of necrotizing keratitis caused by acyclovir (ACV-resistant herpes simplex virus (HSV with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances.

  2. Intravenous Foscarnet With Topical Cidofovir for Chronic Refractory Genital Herpes in a Patient With AIDS

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    Agnes Usoro BSN

    2015-12-01

    Full Text Available Few case reports have documented the use of topical cidofovir for refractory genital herpes simplex virus (HSV ulcers in human immunodeficiency virus (HIV infected patients. This drug formulation lacks a standardized concentration or even a procedural outline as to how it should be compounded. We aim to discuss the utilization of topical cidofovir in addition to presenting a procedural means of compounding it for treatment of refractory genital HSV ulcers. Our patient completed 21 days of intravenous foscarnet and 13 days of topical cidofovir with clinical improvement in the penile and scrotal ulcers. Genital herpes is a concern in patients with HIV because it generally manifests as a persistent infection. Physicians should be aware that when patients fail to respond to the conventional treatment regimens for genital HSV in a timely manner, other options are available, such as topical cidofovir as an adjuvant to systemic antivirals.

  3. Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions

    Energy Technology Data Exchange (ETDEWEB)

    DeLuca, N.; Bzik, D.; Person, S.; Snipes, W.

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyanate (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 ..mu..g/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 ..mu..g/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell.

  4. Early events in herpes simplex virus type 1 infection: photosensitivity of fluorescein isothiocyanate-treated virions.

    Science.gov (United States)

    DeLuca, N; Bzik, D; Person, S; Snipes, W

    1981-02-01

    Herpes simplex virus type 1 is photosensitized by treatment with fluorescein isothiocyante (FITC). The inactivation of FITC-treated virions upon subsequent exposure to light is inhibited by the presence of sodium azide, suggesting the involvement of singlet oxygen in the process. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that treatment with FITC plus light induces crosslinks in viral envelope glycoproteins. Treatment of virions with high concentrations of FITC (50 micrograms/ml) plus light causes a reduction in the adsorption of the virus to monolayers of human embryonic lung cells. For lower concentrations of FITC (10 micrograms/ml) plus light, treated virions adsorb to the host cells, but remain sensitive to light until entry occurs. The loss of light sensitivity coincides with the development of resistance to antibodies. These results are most consistent with a mechanism of entry for herpes simplex virus involving fusion of the viral membrane with the plasma membrane of the host cell. PMID:6262783

  5. Anti-Human Endoglin (hCD105 Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

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    Begoña Barriuso

    2016-06-01

    Full Text Available Endoglin (CD105 is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio propionate (SPDP. The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

  6. A Study of Monocyte Excretion of TNF-a and IL-6 and Monocyte Expression of HLA Class Ⅱ Antigen in Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    敖俊红; 周礼义; 陈兴平; 杨蓉娅; 宋克敏

    2004-01-01

    Objective: To study the role of monocytes in the pathogenesis of genital herpes. Methods: TNF-a and IL-6 levels in 27 cases of genital herpes were detected by enzyme linked immunosorbant assay (ELISA). HLA class Ⅱ antigen expression on monocytes were detected by an alkaline phosphatase anti-alkaline phosphatase method. Results: Compared with normal controls, levels of TNF-a and IL-6 secreted by monocytes responding to LPS mitogen in vitro were significantly decreased [(3.13±0.44ng/ml) vs (4.68±0.54ng/ml),P<0.05 and (3.32±1.06ng/ml) vs (6.46±1.94ng/ml), P<0.05, respectively]. HLA class Ⅱ antigen expression on monocytes in the genital herpes groupwas also significantly decreased [HLA-DR (67.48%± 1.51%) vs (81.03%±1.32%), P<0.01 and HLA-DQ (29.54%±1.15%) vs (37.63%±1.79%), P<0.01 respectively]. Conclusion: These findings suggest that the decreased monocyte function may contribute to the pathogenesis of genital herpes. Augmenting or inducing monocyte function may be important in the prevention, treatment, and reduction of genital herpes cases.

  7. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

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    Masahiko Mihara

    2011-02-01

    Full Text Available Masahiko Mihara1, Yoshiyuki Ohsugi2, Tadamitsu Kishimoto31Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan; 2Chugai Pharmaceutical Co Ltd, Tokyo, Japan; 3Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, JapanAbstract: Interleukin (IL-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-κB ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on naïve T helper cells to promote Th17 cell differentiation. Thus, an imbalance between T cell subsets possibly contributes to development of rheumatoid arthritis. Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis. Tocilizumab prevented radiographic progression of joint destruction by inhibiting cartilage/bone resorption. Tocilizumab also improved hematological abnormalities, including hypergammaglobulinemia, high levels of autoantibodies, and elevation of erythrocyte sedimentation rate and acute-phase proteins. Importantly, tocilizumab improved quality of life by reducing systemic symptoms, including fatigue, anemia, anorexia, and fever. These findings have confirmed that hyperproduction of IL-6 is responsible for the above clinical symptoms, including joint destruction. Many patients treated with tocilizumab achieved clinical remission associated with decreased serum IL-6, suggesting that IL-6 enhances autoimmunity. Tocilizumab is a new therapeutic option for rheumatoid arthritis

  8. Characterization of a recombinant humanized anti-cocaine monoclonal antibody and its Fab fragment.

    Science.gov (United States)

    Kirley, Terence L; Norman, Andrew B

    2015-01-01

    Variations of post-translational modifications are important for stability and in vivo behavior of therapeutic antibodies. A recombinant humanized anti-cocaine monoclonal antibody (h2E2) was characterized for heterogeneity of N-linked glycosylation and disulfide bonds. In addition, charge heterogeneity, which is partially due to the presence or absence of C-terminal lysine on the heavy chains, was examined. For cocaine overdose therapy, Fab fragments may be therapeutic, and thus, a simplified method of generation, purification, and characterization of the Fab fragment generated by Endoproteinase Lys-C digestion was devised. Both the intact h2E2 antibody and purified Fab fragments were analyzed for their affinities for cocaine and 2 of its metabolites, benzoylecgonine and cocaethylene, by fluorescence quenching of intrinsic antibody tyrosine and tryptophan fluorescence resulting from binding of these drugs. Binding constants obtained from fluorescence quenching measurements are in agreement with recently published radioligand and ELISA binding assays. The dissociation constants determined for the h2E2 monoclonal and its Fab fragment are approximately 1, 5, and 20 nM for cocaethylene, cocaine, and benzoylecgonine, respectively. Tryptophan fluorescence quenching (emission at 330 nm) was measured after either excitation of tyrosine and tryptophan (280 nm) or selective excitation of tryptophan alone (295 nm). More accurate binding constants are obtained using tryptophan selective excitation at 295 nm, likely due to interfering absorption of cocaine and metabolites at 280 nm. These quenching results are consistent with multiple tryptophan and tyrosine residues in or near the predicted binding location of cocaine in a previously published 3-D model of this antibody's variable region.

  9. Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes

    OpenAIRE

    Ito, Minoru; Nagasawa, Michiaki; Hara, Tomoko; Ide, Tomohiro; Murakami, Koji

    2010-01-01

    Both insulin and the cell death-inducing DNA fragmentation factor-α-like effector (CIDE) family play important roles in apoptosis and lipid droplet formation. However, regulation of the CIDE family by insulin and the contribution of the CIDE family to insulin actions remain unclear. Here, we investigated whether insulin regulates expression of the CIDE family and which subtypes contribute to insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes. Insulin decreased CIDE...

  10. Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

    OpenAIRE

    Elena Sandalova; Diletta Laccabue; Carolina Boni; Tan, Anthony T.; Katja Fink; Eng Eong Ooi; Robert Chua; Bahar Shafaeddin Schreve; Carlo Ferrari; Antonio Bertoletti

    2010-01-01

    Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 1...

  11. Cytotoxicity of an ebulin l-anti-human CD105 immunotoxin on mouse fibroblasts (L929) and rat myoblasts (L6E9) cells expressing human CD105.

    Science.gov (United States)

    Benítez, Jorge; Ferreras, J Miguel; Muñoz, Raquel; Arias, Yolanda; Iglesias, Rosario; Córdoba-Díaz, Manuel; del Villar, Rosario; Girbés, Tomás

    2005-01-01

    Tumour growth is characterised by the formation of a fine vessel network or neovasculature which nourishes tumour cells. Two kinds of novel anti-angiogenic therapies are based on the prevention of vessels growth and on the destruction of those vessels already formed. We report here on the design and construction of a novel immunotoxin formed with the non-toxic type II ribosome-inactivating protein ebulin l and the mouse anti-human CD105 monoclonal antibody 44G4. The 44G4-ebulin immunotoxin was formed by covalent linking of both proteins with N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) and was purified by chromatography on Superdex 200 HiLoad. The analysis of the anti-ribosomal effects in a cell-free translation system indicated that conjugation does not affect the activity of ebulin l. The immunotoxin displays cytotoxicity with nanomolar IC50 values on human CD105+ cells like the mouse fibroblasts L929 cells transfected with the short form of human CD105 and the rat myoblasts L6E9 transfected with the long form of human CD105. In contrast, cells lacking human CD105 were 2-2.5 logs less sensitive to the immunotoxin. Free ebulin displays IC50 values in the range 10(-6) M. Since CD105 is being considered as a potential target for the anti-vascular therapy of tumours, the present immunotoxin could be a promising tool for the anticancer therapy, especially due to the very low in vivo toxicity of ebulin l as compared ricin and other toxins used for immunotoxins.

  12. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Yanxi [Department of Biology, Lakehead University, Thunder Bay (Canada); College of Life Science, Shanxi University, Taiyuan (China); Wu, Bo [Department of Biology, Lakehead University, Thunder Bay (Canada); Department of Pathophysiology, Harbin Medical University, Harbin (China); Cao, Qiuhui [Department of Biology, Lakehead University, Thunder Bay (Canada); Wu, Lingyun [Department of Pathophysiology, Harbin Medical University, Harbin (China); Department of Pharmacology, University of Saskatchewan, Saskatoon (Canada); Yang, Guangdong, E-mail: gyang@lakeheadu.ca [The School of Kinesiology, Lakehead University, Thunder Bay (Canada)

    2011-12-15

    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of

  13. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    International Nuclear Information System (INIS)

    Hydrogen sulfide (H2S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H2S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H2S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H2S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H2S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H2S-producing enzyme in prostate. CSE overexpression enhanced H2S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H2S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H2S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H2S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: ► A large amount of H2S is released from sulforaphane. ► H2S mediates the anti-survival effect of sulforaphane on human prostate cancer cells. ► Cystathionine gamma-lyase is a major H2S-producing enzyme in prostate tissues.

  14. Presence of anti-Toxoplasma antibodies in humans and their cats in the urban zone of Guadalajara

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    Galván Ramírez María de la Luz

    1999-01-01

    Full Text Available Cats are the definitive hosts of Toxoplasma gondii. Infected cats excrete oocysts in their feces, infecting humans and other animals. The objective of the present study was to determine the presence of anti-Toxoplasma antibodies in cat owners and their pets, and determine if there was a relationship between Toxoplasma infection and humans who live with infected cats. IgG anti-Toxoplasma antibodies in sera of 59 cat owners were determined by enzyme-linked immunosorbent assay (ELISA, in 24 sera from their cats, IgG, IgM, and IgA antibodies were found using Burney's ELISA. Thirty-eight (64% of 59 cat owners were positive to IgG anti-Toxoplasma. Seropositivity for cats was 70.8% IgG, 8.3% IgM, and 62.5% IgA. Cohabitation with cats infected by T. gondii, feeding with leftovers or raw viscera, and lack of control over how their feces were handled are risk factors conducive for humans to become infected by T. gondii.

  15. Conditional expression of full-length humanized anti-prion protein antibodies in Chinese hamster ovary cells.

    Science.gov (United States)

    Mueller, Daniel A; Heinig, Lars; Ramljak, Sanja; Krueger, Astrid; Schulte, Reiner; Wrede, Arne; Stuke, Andreas W

    2010-12-01

    Because of their high antigen specificity and metabolic stability, genetically engineered human monoclonal antibodies are on the way to becoming one of the most promising medical diagnostics and therapeutics. In order to establish an in vitro system capable of producing such biosimilar antibodies, we used human constant chain sequences to design the novel human antibody expressing vector cassette pMAB-ABX. A bidirectional tetracycline (tet)-controllable promotor was used for harmonized expression of immunoglobulin type G (IgG) heavy and light chains. As an example we used anti-prion protein (anti-PrP) IgGs. Therefore, the variable heavy (V(H)) and light chain (V(L)) sequences of anti-PrP antibodies, previously generated in our laboratory by DNA immunization of prion protein knock-out mice, were isolated from murine hybridoma cell lines and inserted into pMAB-ABX vector. After transfection of Chinese hamster ovary (CHO) cells, a number of stable antibody producing cell clones were selected. One cell line (pMAB-ABX-13F10/3B5) stably expressing the recombinant humanized antibody (rechuAb) 13F10/3B5 was selected for detailed characterization by Western blot, immunofluorescence, and flow cytometric analyses. The full-length recombinant humanized IgG antibody showed a high level of expression in the cytoplasm. In conclusion, the new cell system described here is a suitable tool to produce functional intact full-length humanized IgG antibodies. PMID:21087094

  16. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan;

    2011-01-01

    been shown to halve the risk of HZ, and the risk of PHN is reduced by two thirds in people = 60 years. The vaccine is approved for persons aged = 50 years. However, the clinical efficacy of the vaccine is best studied in people aged = 60 years. The vaccine has so far not shown any serious side-effects.......Herpes zoster (HZ) and post-herpetic neuralgia (PHN) are frequently occurring diseases in elderly and in immuno-compromised persons. The live attenuated HZ vaccine boosts an existing immune response, so that the already established varicella-zoster virus infection is kept latent. Vaccination has...

  17. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan;

    2011-01-01

    Herpes zoster (HZ) and post-herpetic neuralgia (PHN) are frequently occurring diseases in elderly and in immuno-compromised persons. The live attenuated HZ vaccine boosts an existing immune response, so that the already established varicella-zoster virus infection is kept latent. Vaccination has...... been shown to halve the risk of HZ, and the risk of PHN is reduced by two thirds in people = 60 years. The vaccine is approved for persons aged = 50 years. However, the clinical efficacy of the vaccine is best studied in people aged = 60 years. The vaccine has so far not shown any serious side-effects....

  18. A Recombinant Humanized Anti-Cocaine Monoclonal Antibody Inhibits the Distribution of Cocaine to the Brain in Rats

    OpenAIRE

    Norman, Andrew B.; Gooden, Felicia C. T.; Tabet, Michael R.; Ball, William J.

    2014-01-01

    The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benzoylecgonine (BE) and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg i.v.) showed a long terminal elimination half-life of 9.0 days and a low volume of distribution at st...

  19. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia

    Science.gov (United States)

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements opening perspectives for the prevention of FNAIT. PMID:27627660

  20. Prokaryotic Selectivity, Anti-endotoxic Activity and Protease Stability of Diastereomeric and Enantiomeric Analogs of Human Antimicrobial Peptide LL-37

    Energy Technology Data Exchange (ETDEWEB)

    Nan, Yong Hai; Lee, Bongju; Shin, Song Yub [Chosun Univ., Gwangju (Korea, Republic of)

    2012-09-15

    LL-37 is the only antimicrobial peptide (AMP) of the human cathelicidin family. In addition to potent antimicrobial activity, LL-37 is known to have the potential to inhibit lipolysaccharide (LPS)-induced endotoxic effects. To provide the stability to proteolytic digestion and increase prokaryotic selectivity and/or anti-endotoxic activity of two Lys/Trp-substituted 19-meric anti-microbial peptides (a4-W1 and a4-W2) designed from IG-19 (residues 13-31 of LL-37), we synthesized the diastereomeric peptides (a4-W1-D and a4-W2-D) with D-amino acid substitution at positions 3, 7, 10, 13 and 17 of a4-W1 and a4-W2, respectively and the enantiomeric peptides (a4-W1-E and a4-W2-E) composed D-amino acids. The diastereomeric peptides exhibited the best prokaryotic selectivity and effective protease stability, but no or less anti-endotoxic activity. In contrast, the enantiomeric peptides had not only prokaryotic selectivity and anti-endotoxic activity but also protease stability. Our results suggest that the hydrophobicity and α-helicity of the peptide is important for anti-endotoxic activity. In particular, the enantiomeric peptides showed potent anti-endotoxic and LPS-neutralizing activities comparable to that of LL-37. Taken together, both a4-W1-E and a4-W2-E holds promise as a template for the development of peptide antibiotics for the treatment of endotoxic shock and sepsis.

  1. Human synthetic lethal inference as potential anti-cancer target gene detection

    OpenAIRE

    Solé Ricard V; Munteanu Andreea; Conde-Pueyo Nuria; Rodríguez-Caso Carlos

    2009-01-01

    Abstract Background Two genes are called synthetic lethal (SL) if mutation of either alone is not lethal, but mutation of both leads to death or a significant decrease in organism's fitness. The detection of SL gene pairs constitutes a promising alternative for anti-cancer therapy. As cancer cells exhibit a large number of mutations, the identification of these mutated genes' SL partners may provide specific anti-cancer drug candidates, with minor perturbations to the healthy cells. Since exi...

  2. Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody

    International Nuclear Information System (INIS)

    Introduction: We previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting. Methods: Specific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus 111In-labeled cMORF to direct targeting by 111In-labeled HPi1. Results: HPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ 111In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting. Conclusions: Pretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ.

  3. A REVIEW ARTICLE ON HERPES SIMPLEX ENCEPHALITIS

    Directory of Open Access Journals (Sweden)

    A. Karimi MD,

    2007-02-01

    Full Text Available Herpes Simplex encephalitis (HSE is a life threatening outcome of Herpes simplex virus (HSV infection of the central nervous system (CNS. HSVaccounts for 2-5 percent of all cases of encephalitis. One third of cases occur in those younger than 20 years old and one half in those older than 50 years old.Clinical diagnosis is recommended in the encephalopathic, febrile patients with focal neurological signs. However, the clinical findings are not pathogonomic because numerous other diseases of CNS can mimic HSE. Diagnosis should be confirmed based on medical history, analysis of cerebrospinal fluid (CSF for protein and glucose contents, the cellular analysis and identifying the pathogens by serology and Polymerase Chain Reaction (PCR amplification .The diagnostic gold standard is the detection of HSV DNA in the cerebrospinal fluid by PCR. But negative results need to be interpreted regarding thepatients clinical signs and symptoms and the time of CSF sampling. Spike and slow wave patterns is observed in Electroencephalogram (EEG.Neuroimaging, especially Magnetic Resonance Imaging (MRI is essential for evaluating the patients, which shows temporal lobe edema or hemorrhage.All patients with HSE should be treated by intravenous Acyclovir (10mg/kg q8hr for 14-21 days. After completing therapy, PCR of the CSF can confirmthe elimination of replicating virus, assisting further management of the patient.

  4. Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Servin, Alain L

    2014-04-01

    A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract.

  5. Candidate Topical Microbicides Bind Herpes Simplex Virus Glycoprotein B and Prevent Viral Entry and Cell-to-Cell Spread

    OpenAIRE

    Cheshenko, Natalia; Keller, Marla J.; MasCasullo, Veronica; Jarvis, Gary A.; Cheng, Hui; John, Minnie; Li, Jin-Hua; Hogarty, Kathleen; Anderson, Robert A.; Waller, Donald P.; Lourens J. D. Zaneveld; Profy, Albert T.; Klotman, Mary E.; Herold, Betsy C.

    2004-01-01

    Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observation that herpes simplex virus (HSV) and human immunodeficiency virus bind heparan sulfate provided the rationale for the development of sulfated or sulfonated polymers as topical agents. Although several of the polymers have advanced to clin...

  6. Antihyperalgesic effects of infection with a preproenkephalin-encoding herpes virus

    OpenAIRE

    Wilson, Steven P.; Yeomans, David C; Bender, Mary Ann; Lu, Ying; Goins, William F; Glorioso, Joseph C.

    1999-01-01

    To test the utility of gene therapeutic approaches for the treatment of pain, a recombinant herpes simplex virus, type 1, has been engineered to contain the cDNA for an opioid peptide precursor, human preproenkephalin, under control of the human cytomegalovirus promoter. This virus and a similar recombinant containing the Escherichia coli lacZ gene were applied to the abraded skin of the dorsal hindpaw of mice. After infection, the presence of β-galactosidase in neuronal cell bodies of the re...

  7. Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis.

    Science.gov (United States)

    Jansen, Laura; Vos, Xander G; Löwenberg, Mark

    2016-02-16

    We here present the case of a 22-year-old female of Suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. She presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (HSV-1). Combination therapy consisting of immunomodulators and anti-tumor necrosis factor (TNF) agents is increasingly being used. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. We here show that HSV infections can cause a severe tonsillitis in immunocompromised patients. Early recognition is essential when there is no improvement with initial antibiotic therapy within the first 24 to 72 h. HSV infections should be in the differential diagnosis of immunocompromised patients presenting with a necrotizing tonsillitis and can be confirmed by polymerase chain reaction. Early treatment with antiviral agents should be considered especially if antibiotic treatment fails in such patients. PMID:26881193

  8. Biomarkers of (anti)oxidant status in human nutrition, aging and disease

    OpenAIRE

    Jansen, Eugene; Beekhof, Piet; Cremers, Johannes; Ruskovska, Tatjana

    2015-01-01

    The (anti)oxidant status of individuals is an important factor for the risks of chronic diseases. Biomarker measurements in serum/plasma is a good way to determine the status of the oxidant/antioxidant balance. From our own experience, we come to a proposal of a set of biomarkers for nutritional intake of antioxidants to determine the (anti)oxidant status in serum as a reflection of nutrition. Serum concentrations of biomarkers of fat-soluble vitamins are not suitable to assess ...

  9. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    Science.gov (United States)

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements

  10. Anti-wrinkle effects of a tuna heart H2O fraction on Hs27 human fibroblasts.

    Science.gov (United States)

    Kim, Young-Min; Jung, Hee-Jin; Choi, Jae-Sue; Nam, Taek-Jeong

    2016-01-01

    With the increase in life expectancy, there is also growing interest in anti-aging treatments and technologies. The development of anti-aging functional drugs for the skin, and foods from natural sources, may offer solutions to this global matter. Aging involves structural, functional and biochemical changes that occur throughout cells and bodily tissues; the amount of hormones secreted from of all human organs, including the skin, decreases over time. Matrix metalloproteinase (MMP) genes (MMP-1 and -8) play an important role in the aging of skin fibroblasts. For example, an increased MMP expression causes accelerated aging and the degradation of skin elasticity-related genes. In the present study, we examined the anti-wrinkle effects of tuna heart extract which are mediated through the inhibition of MMPs in skin cells. Generally, tuna contains high concentrations of selenium and antioxidants, which serve to remove free radicals, and is known to delay skin and body aging. In addition, unsaturated fatty acids in tuna help to maintain the natural glossy look of skin, and increase skin elasticity, providing moisture for dry skin. A recent study confirmed the various bio-effects of boiled tuna extract and muscle. However, bioactivity studies using tuna heart are limited. Thus, in the present study, we obtained extracts and fractions of tuna heart, and examined their effects on Hs27 human fibroblast proliferation using an MTS assay. In addition, we measured procollagen type 1 levels and elastase activity, and performed β-galactosidase staining. We then measured the expression levels of phosphatidylinositol 3-kinase/Akt and MMP-related genes by western blot analysis and RT-PCR. Our results revealed that tuna heart extract decreased MMP expression by upregulating tissue inhibitors of metalloproteinase-1 (TIMP-1) and decreasing elastase activity, thus exerting anti-aging and anti-wrinkle effects by increasing collagen synthesis and promoting skin fibroblast

  11. Anti-apoptotic effects of recombinant human granulocyte colony-stimulating factor in focal cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    Xia Yuan; Shiming Zhang; Wanli Dong; Qi Fang

    2011-01-01

    The neuroprotective effects of granulocyte colony-stimulating factor in cerebral ischemia/reperfusion injury are currently contentious. The present study examined the effects of subcutaneous injection of recombinant human granulocyte colony-stimulating factor (50 μg/kg) over 5 days in a model of cerebral ischemia/reperfusion with intraluminal filament occlusion in rats. The results indicated that recombinant human granulocyte colony-stimulating factor reduced brain infarct volume following cerebral ischemia/reperfusion injury in rats, down-regulated the expression of caspase-3 mRNA (a key protease for apoptosis in the cerebral ischemia zone), lowered the rate of neuronal apoptosis in the cerebral ischemia zone, and notably ameliorated neurological function. These results indicate that recombinant human granulocyte colony-stimulating factor has anti-apoptotic effects on neurons following focal cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

  12. Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA.

    Science.gov (United States)

    Ruiz-Ramos, Alba; Velázquez-Campoy, Adrián; Grande-García, Araceli; Moreno-Morcillo, María; Ramón-Maiques, Santiago

    2016-07-01

    CAD, the multienzymatic protein that initiates and controls de novo synthesis of pyrimidines in animals, associates through its aspartate transcarbamoylase (ATCase) domain into particles of 1.5 MDa. Despite numerous structures of prokaryotic ATCases, we lack structural information on the ATCase domain of CAD. Here, we report the structure and functional characterization of human ATCase, confirming the overall similarity with bacterial homologs. Unexpectedly, human ATCase exhibits cooperativity effects that reduce the affinity for the anti-tumoral drug PALA. Combining structural, mutagenic, and biochemical analysis, we identified key elements for the necessary regulation and transmission of conformational changes leading to cooperativity between subunits. Mutation of one of these elements, R2024, was recently found to cause the first non-lethal CAD deficit. We reproduced this mutation in human ATCase and measured its effect, demonstrating that this arginine is part of a molecular switch that regulates the equilibrium between low- and high-affinity states for the ligands.

  13. Anti-GaL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation.

    Science.gov (United States)

    Minanov, O P; Itescu, S; Neethling, F A; Morgenthau, A S; Kwiatkowski, P; Cooper, D K; Michler, R E

    1997-01-27

    We have previously demonstrated that hyperacute rejection does not occur in a pig-to-newborn baboon heart transplant model, presumably because of low levels of cytotoxic antipig antibodies present in the serum of newborn baboons. Cytotoxic antipig antibodies are primarily directed to alpha-1,3-galactosyl (alpha Gal) residues on endothelial cell surface structures Twenty-one full-term humans and 5 full-term baboons were tested for complement mediated lysis (CML) of pig kidney (PK-15) cells and anti-alpha Gal activity with an ELISA using BSA-conjugated alpha Gal residues as target. To evaluate the significance of the anti-alpha Gal titers in vivo 5 newborn baboons underwent heterotopic pig cardiac xenotransplantation. Six of 21 human samples and 1 of 5 baboon samples demonstrated significant cytotoxicity to PK-15 cells. Twelve of 21 newborn humans had anti-alpha Gal IgG antibodies at titers of 1:80 or greater. None of the samples had anti-alpha Gal IgM. In newborn baboons, 1 of 5 sera had anti-alpha Gal IgG antibodies at titers greater than 1:80 and none of these samples had anti-alpha Gal IgM. Xenografts survived for an average of 3.6 days, even in the baboon with high anti-alpha Gal IgG titers. Analysis of the explanted grafts showed minimal evidence of complement-mediated hyperacute rejection (HAR), but prominent mononuclear cell infiltrates. In serum tested posttransplant there was an induced anti-alpha Gal response with cytotoxicity against PK-15 cells. These results show that anti-alpha Gal IgM is absent in newborn human and baboon sera, allowing pig grafts to avoid HAR. However, the presence of anti-alpha Gal IgG may be associated with mononuclear cell infiltration of the xenograft and its subsequent rejection. PMID:9020315

  14. Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

    DEFF Research Database (Denmark)

    Mamsen, Linn; Petersen, TS; Jeppesen, JV;

    2015-01-01

    From early embryonic life, anti-Müllerian hormone (AMH) is produced by Sertoli cells and is essential for male sex differentiation. In females, AMH is produced by immature granulosa cells (GCs) but a definitive function in females is uncertain. We have assessed the cellular localization and speci...

  15. Reactivation of herpes simplex virus-1 following epilepsy surgery

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2015-01-01

    Conclusion: The authors stress the potential risk of reactivation of HSV encephalitis after intracranial surgery. Herpes simplex virus encephalitis must be considered in neurosurgical patients who develop postoperative seizures and fever.

  16. Herpes zoster on the face in the elderly.

    Science.gov (United States)

    Nair, Preeti; Gharote, Harshkant; Singh, Pooja; Jain-Choudhary, Palak

    2014-01-01

    Herpes zoster is a localised disease caused by reactivation of the varicella zoster virus that enters the cutaneous nerve endings during an earlier episode of chicken pox, travels to the dorsal root ganglia, and remains in latent form. The condition is characterised by occurrence of multiple, painful, unilateral vesicles and ulceration, and shows a typical single dermatome innervated by single dorsal root or cranial sensory ganglion. Involvement of three or more dermatomes is known as disseminated zoster and seen in immunocompromised individuals. Complications of herpes zoster include ocular sequelae, bacterial superinfection of the lesions, meningoencephalitis and postherpetic neuralgia. The incidence of herpes zoster increases with age and immunosuppression, therefore prompt management is necessary to avoid morbidity and mortality in these individuals. We present two case reports of herpes zoster, one involving the maxillary and mandibular branches of the trigeminal nerve while the other involves all branches of the trigeminal nerve. PMID:25331144

  17. Herpes zoster on segmental vitiligo: Wolf’s isotopic response?

    Directory of Open Access Journals (Sweden)

    Mankesh Lal Gambhir

    2014-04-01

    Full Text Available “Wolf’s isotopic response” describes the occurrence of a new skin disorder at the site of another, unrelated and already healed skin disease. In most cases of isotopic response, the initial dermatosis is herpes zoster, herpes simplex, varicella, thrombophlebitis, scrofuloderma and striae distense. The most frequent second dermatoses are granulomatous reactions, particularly granuloma annulare, and lichenoid diseases. Various etiological reasons including viral, immunologic, neural and vascular have been put forth. We report here a case in which the second disease was herpes zoster that appeared over the same dermatomes of pre-existing segmental vitiligo. The occurrence of vitiligo as first and herpes zoster as second disease in the “Wolf’s isotopic response” has not, to the best of our knowledge, been reported previously.

  18. Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Yusuf, Isharat; Akhgar, Ahmad; Wu, Yuling; Roskos, Lorin K; Herbst, Ronald; Wang, Yue

    2016-07-01

    B cell depletion therapy is beneficial for patients with B cell malignancies and autoimmune diseases. CD19, a transmembrane protein, is expressed on a vast majority of normal and neoplastic B cells, making it a suitable target for monoclonal antibody (MAb) mediated immunotherapy. We have developed MEDI-551, an affinity optimized and afucosylated IgG1 MAb targeting human CD19 for B cell depletion. MEDI-551 is currently under investigation in multiple clinical trials. Because MEDI-551 does not cross react with rodent and non-human primate CD19, the pharmacological characteristics of the MAb were evaluated in human CD19 transgenic mice (hCD19 Tg). Here we show that MEDI-551 potently depletes tissue and circulating B cells in hCD19 Tg mice and is more efficacious than the anti-CD19 MAb with intact fucose. The length of B cell depletion depends on MEDI-551 dose; and, B cell recovery in the circulation follows stepwise phenotypic maturation. Furthermore, intravenous (IV) and subcutaneous (SC) administration of MEDI-551 results in comparable efficacy. Lastly, the combination of MEDI-551 with the anti-CD20 MAb, rituximab, further prolongs the duration of B cell depletion. In summary, the pharmacological profile of MEDI-551 presented in hCD19 Tg mice supports further testing of MEDI-551 in clinical trials involving B cell malignancies and autoimmune diseases. PMID:27163209

  19. TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis.

    Science.gov (United States)

    Yorozuya, Kyoko; Kubota, Tetsuro; Watanabe, Masahiko; Hasegawa, Hirotoshi; Ozawa, Soji; Kitajima, Masaki; Chikahisa, Lumi Muramatsu; Yamada, Yuji

    2005-09-01

    A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.

  20. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review

    Directory of Open Access Journals (Sweden)

    Nebel Almut

    2010-01-01

    Full Text Available Abstract Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex. ApoE4 seems to be protective against chronic hepatitis C virus infection and retards fibrosis progression. In contrast apoE4 enhances the fusion rate of human immunodeficiency virus with target cell membranes, resulting in accelerated cell entry and faster disease progression. Its association with human immunodeficiency virus-associated dementia remains controversial. Regarding herpes simplex virus infection, apoE4 intensifies virus latency and is associated with increased oxidative damage of the central nervous system, and there is some evidence that herpes simplex virus infection in combination with the apoE4 genotype may be associated with an increased risk of Alzheimer's disease. In addition to reviewing available data from human trials, evidence derived from a variety of cell culture and animal models are considered in this review in order to provide mechanistic insights into observed association between apoE4 genotype and viral disease infection and pathology.

  1. Prodromal Herpes Zoster Mimicking Odontalgia - A Diagnostic Challenge

    OpenAIRE

    Patil, Shilpa; Srinivas, K.; Reddy, BH Satheesha; Gupta, Mudit

    2013-01-01

    Herpes zoster (shingles) is caused by reactivation of the latent varicella zoster virus which is present due to an earlier varicella infection (chicken-pox). Herpes Zoster is a less common and endemic disease than varicella, although factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Involvement of C3, T5, L1, L2 and first division of trigeminal nerve are the most frequently encountered whereas the involvement of second and thir...

  2. Herpes Zoster Sebagai Salah Satu Etiologi Paralisis Nervus Fasialis

    OpenAIRE

    Sitepu, Rahel Florida

    2008-01-01

    Virus varisela zoster merupakan virus penyebab dari dua infeksi klinis yang utama pada manusia yaitu chicken pox (varisela ) dan shingles (herpes zoster). Chicken pox merupakan infeksi primer yang sifatnya umum, yang terjadi pertama kali pada individu yang berkontak dengan virus tersebut. Setelah infeksi primerya sembuh virus tersebut tetap laten didalam ganglion saraf. Herpes zoster merupakan reaktivasi yang terjadi setelah penderita mendapat varisela. Virus varisela yang menyerang gang...

  3. Evaluation of optimal control type models for the human gunner in an Anti-Aircraft Artillery (AAA) system

    Science.gov (United States)

    Phatak, A. V.; Kessler, K. M.

    1975-01-01

    The selection of the structure of optimal control type models for the human gunner in an anti aircraft artillery system is considered. Several structures within the LQG framework may be formulated. Two basic types are considered: (1) kth derivative controllers; and (2) proportional integral derivative (P-I-D) controllers. It is shown that a suitable criterion for model structure determination can be based on the ensemble statistics of the tracking error. In the case when the ensemble tracking steady state error is zero, it is suggested that a P-I-D controller formulation be used in preference to the kth derivative controller.

  4. In vitro anti-telomerase activity of novel lycopene-loaded nanospheres in the human leukemia cell line K562

    OpenAIRE

    Amir Gharib; Zohreh Faezizadeh

    2014-01-01

    Background: Lycopene, a plant carotenoid, has potent effects against the various types of cancer cells. To date, the effect of lycopene in the free and encapsulated forms on the telomerase activity in human leukemia cell line K562 have not been investigated. The aim of the present study was to prepare a novel lycopene-loaded nanosphere and compare its anti-telomearse activity in K562 cell line with those of free lycopene. Materials and Methods: The lycopene-loaded nanospheres were prepared by...

  5. [Complicated febrile convulsion vs herpes-encephalitis].

    Science.gov (United States)

    Millner, M

    1993-01-01

    Since Acyclovir is available a sufficient treatment of herpes simplex virus (HSV) encephalitis exists. Febrile convulsions may occur as the initial manifestation of an encephalitis, particularly of an HSV encephalitis. Within 25 months out of 151 children with febrile convulsions five children with complicated febrile convulsions were admitted at the pediatric department of Graz. In all children HSV antibodies in serum and cerebrospinal fluid (CSF) were negative and the diagnosis of an HSV encephalitis was made by positive CSF HSV polymerase chain reaction (PCR). Therefore, in any suspected case, i.e. in any case of a complicated febrile convulsion, CSF should be investigated including a HSV PCR to rapidly confirm or exclude HSV encephalitis. PMID:8386831

  6. [Immunopathological findings in herpes gestationis (author's transl)].

    Science.gov (United States)

    Scherer, R; Wolff, H H; Braun-Falco, O

    1977-08-12

    Herpes gestationis occurred in a 26-year-old woman during the last weeks of her second pregnancy. Within 8 days of the delivery the disease had progressed to such an extent that systemic treatment became necessary. Whereas pre-delivery treatment had consisted exclusively of local desinfection, and steroid and antibiotic ointments, treatment after delivery also included systemic use of prednisolone. After treatment for 3 weeks the skin changes had disappeared except for minimal pigmentation. Using immunofluorescent microscopy a complement activation in the dermo-epidermal junction and in adjacent clinically healthy skin could be demonstrated: There were massive linear depositions of C3, C1q and C4. In the basal membrane of the epidermis IgM could be demonstrated as an unusual finding. Further immunopathological features were found in the form of an immune complex vasculitis which could be shown during the active phase of the disease.

  7. Immunomodulating and antiviral therapy in herpes zoster.

    Science.gov (United States)

    Topciu, V; Mihăilescu, R

    1996-01-01

    Two groups of patients with herpes zoster were followed up. The first group was subjected, beside a symptomatic therapy, to an immunological and antiviral treatment. The control group was treated only symptomatically. The immunological preparations used were: the immunostimulant SRE (Corynebacterium parvum), which stimulated the lymphocytes and macrophages, Moroxidin (Virustat-Paris) and Antiherpin (interferon inductor), which acted by blocking the virus replication. The preparations were indigenous and atoxic. A significant difference between the courses of disease in the two groups was observed, namely, the severity and duration of subjective and objective symptoms were more than double and followed by persistent neurological sequelae in the control group in comparison with the patients of the experimental group. PMID:9495784

  8. Localized Eruptive Blue Nevi after Herpes Zoster

    Science.gov (United States)

    Colson, Fany; Arrese, Jorge E.; Nikkels, Arjen F.

    2016-01-01

    A 52-year-old White man presented with a dozen small, well-restricted, punctiform, asymptomatic, blue-gray macules on the left shoulder. A few months earlier, he had been treated with oral acyclovir for herpes zoster (HZ) affecting the left C7–C8 dermatomes. All the blue macules appeared over a short period of time and then remained stable. The patient had not experienced any previous trauma or had tattooing in this anatomical region. The clinical diagnosis suggested blue nevi. Dermatoscopy revealed small, well-limited, dark-blue, compact, homogeneous areas evoking dermal blue nevi. An excisional biopsy was performed and the histological examination confirmed a blue nevus. As far as we are aware of, this is the first report of eruptive blue nevi following HZ, and it should be included in the differential diagnosis of zosteriform dermatoses responding to an isotopic pathway. In addition, a brief review concerning eruptive nevi is presented. PMID:27462219

  9. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study

    Science.gov (United States)

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell’Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  10. Body Image and Anti-Fat Attitudes: An Experimental Study Using a Haptic Virtual Reality Environment to Replicate Human Touch.

    Science.gov (United States)

    Tremblay, Line; Roy-Vaillancourt, Mélina; Chebbi, Brahim; Bouchard, Stéphane; Daoust, Michael; Dénommée, Jessica; Thorpe, Moriah

    2016-02-01

    It is well documented that anti-fat attitudes influence the interactions individuals have with overweight people. However, testing attitudes through self-report measures is challenging. In the present study, we explore the use of a haptic virtual reality environment to physically interact with overweight virtual human (VH). We verify the hypothesis that duration and strength of virtual touch vary according to the characteristics of VH in ways similar to those encountered from interaction with real people in anti-fat attitude studies. A group of 61 participants were randomly assigned to one of the experimental conditions involving giving a virtual hug to a female or a male VH of either normal or overweight. We found significant associations between body image satisfaction and anti-fat attitudes and sex differences on these measures. We also found a significant interaction effect of the sex of the participants, sex of the VH, and the body size of the VH. Female participants hugged longer the overweight female VH than overweight male VH. Male participants hugged longer the normal-weight VH than the overweight VH. We conclude that virtual touch is a promising method of measuring attitudes, emotion and social interactions.

  11. Simultaneous determination of five anti-epilepsy drugs in human plasma using liquid chromatography-mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    STEFANIE; WeiBig

    2010-01-01

    A new liquid chromatography-mass spectrometry method for the determination of carbamazepine,clonazepam,alprazolam,estazolam and phenytoin in human plasma has been developed by using diazepam as an internal standard.Chromatographic separation was performed on a Zorbax SB-C18 column(30 mm × 2.1 mm,3.5 ?m) with a mobile phase consisting of methanol and aqueous 25 mM ammonium acetate using gradient elution.A diethyl ether extraction method was used for the extraction of five anti-epilepsy drugs.The final extract was injected for analysis by LC-MS/MS.The method was validated within the concentration range of 50-5000 ng mL-1 for five anti-epilepsy drugs.The precision of the assay(RSD%) was less than 10% at all concentration levels within the tested range.The method recoveries for all samples were more than 90%.The results indicate that the method is specific,sensitive and accurate,and suitable to study the pharmacokinetics,to adjust the dosage for individual administration,and to monitor the drug-concentration and drug abuse of the five anti-epilepsy drugs.

  12. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L. in Human Gastric Epithelial Cells: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Chiara Di Lorenzo

    2016-07-01

    Full Text Available Raisins (Vitis vinifera L. are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL-8 and Nuclear Factor (NF-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD analysis and screened for their ability to inhibit Tumor necrosis factor (TNFα-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases.

  13. Evaluation of the Anti-Inflammatory Activity of Raisins (Vitis vinifera L.) in Human Gastric Epithelial Cells: A Comparative Study.

    Science.gov (United States)

    Di Lorenzo, Chiara; Sangiovanni, Enrico; Fumagalli, Marco; Colombo, Elisa; Frigerio, Gianfranco; Colombo, Francesca; Peres de Sousa, Luis; Altindişli, Ahmet; Restani, Patrizia; Dell'Agli, Mario

    2016-01-01

    Raisins (Vitis vinifera L.) are dried grapes largely consumed as important source of nutrients and polyphenols. Several studies report health benefits of raisins, including anti-inflammatory and antioxidant properties, whereas the anti-inflammatory activity at gastric level of the hydro-alcoholic extracts, which are mostly used for food supplements preparation, was not reported until now. The aim of this study was to compare the anti-inflammatory activity of five raisin extracts focusing on Interleukin (IL)-8 and Nuclear Factor (NF)-κB pathway. Raisin extracts were characterized by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD) analysis and screened for their ability to inhibit Tumor necrosis factor (TNF)α-induced IL-8 release and promoter activity in human gastric epithelial cells. Turkish variety significantly inhibited TNFα-induced IL-8 release, and the effect was due to the impairment of the corresponding promoter activity. Macroscopic evaluation showed the presence of seeds, absent in the other varieties; thus, hydro-alcoholic extracts from fruits and seeds were individually tested on IL-8 and NF-κB pathway. Seed extract inhibited IL-8 and NF-κB pathway, showing higher potency with respect to the fruit. Although the main effect was due to the presence of seeds, the fruit showed significant activity as well. Our data suggest that consumption of selected varieties of raisins could confer a beneficial effect against gastric inflammatory diseases. PMID:27447609

  14. Development of Hydrogel with Anti-Inflammatory Properties Permissive for the Growth of Human Adipose Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    R. Sánchez-Sánchez

    2016-01-01

    Full Text Available Skin wound repair requires the development of different kinds of biomaterials that must be capable of restoring the damaged tissue. Type I collagen and chitosan have been widely used to develop scaffolds for skin engineering because of their cell-related signaling properties such as proliferation, migration, and survival. Collagen is the major component of the skin extracellular matrix (ECM, while chitosan mimics the structure of the native polysaccharides and glycosaminoglycans in the ECM. Chitosan and its derivatives are also widely used as drug delivery vehicles since they are biodegradable and noncytotoxic. Regulation of the inflammatory response is crucial for wound healing and tissue regeneration processes; and, consequently, the development of biomaterials such as hydrogels with anti-inflammatory properties is very important and permissive for the growth of cells. In the last years, it has been shown that mesenchymal stem cells have clinical importance in the treatment of different pathologies, for example, skin injuries. In this paper, we describe the anti-inflammatory activity of collagen type 1/chitosan/dexamethasone hydrogel, which is permissive for the culture of human adipose-derived mesenchymal stem cells (hADMSC. Our results show that hADMSC cultured in the hydrogel are viable, proliferate, and secrete the anti-inflammatory cytokine interleukin-10 (IL-10 but not the inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α.

  15. Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

    Science.gov (United States)

    Janse van Rensburg, Walter J

    2016-06-01

    Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID:26559117

  16. In vitro characterization of the human biotransformation of marine derived anti-cancer drugs

    OpenAIRE

    Brandon, E.F.A. (Esther Fleur Annette)

    2004-01-01

    Cancer is the second cause of death in The Netherlands. Although the treatment options over the past few decades have substantially improved, the cure rate for patients with advanced cancer remains low. In addition, hopefully new therapies will induce less severe side effects compared to the present therapies. Overall, new anti cancer drugs are still very much needed to improve treatment outcome of patients. Many active cytotoxic agents originate from natural resources, mainly plants (e.g. pa...

  17. Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital Herpes.

    Directory of Open Access Journals (Sweden)

    Krystle A Lang Kuhs

    Full Text Available IFNL4-ΔG/TT (rs368234815 genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-λ4 protein is generated only in individuals who carry the IFNL4-ΔG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-ΔG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-ΔG/TT with herpes simplex virus (HSV-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS. WIHS is a prospective cohort study of human immunodeficiency virus (HIV-infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV-1 and HSV-2 antibodies at study entry; bi-annually ascertained episodes of (self-reported oral herpes, (self-reported genital sores and (clinician-observed genital ulcers; HSV-2 DNA in cervicovaginal lavage (CVL specimens. IFNL4-ΔG/TT genotyping was determined by TaqMan. We compared women with IFNL4-ΔG/ΔG or IFNL4-TT/ΔG genotypes (i.e., IFNL4-ΔG carriers to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR, 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8% were positive for HSV-1 and 79.0% were positive for HSV-2. We observed no association between IFNL4-ΔG/TT genotype and any outcome: HSV-1 or HSV-2 antibody prevalence (p>0.1, all comparisons; oral herpes (aOR, 1.2; p = 0.35; genital sores (aOR, 1.0; p = 0.71; genital ulcers (aOR, 1.1; p = 0.53; detectable HSV-2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49; HSV-2 DNA level (p = 0.68. In this large prospective study, IFNL4

  18. Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital Herpes

    Science.gov (United States)

    Lang Kuhs, Krystle A.; Kuniholm, Mark H.; Pfeiffer, Ruth M.; Chen, Sabrina; Desai, Seema; Edlin, Brian R.; Peters, Marion G.; Plankey, Michael; Sharp, Gerald B.; Strickler, Howard D.; Villacres, Maria C.; Quinn, Thomas C.; Gange, Stephen J.; Prokunina-Olsson, Ludmila; Greenblatt, Ruth M.; O’Brien, Thomas R.

    2015-01-01

    IFNL4-ΔG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-λ4 protein is generated only in individuals who carry the IFNL4-ΔG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-ΔG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-ΔG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women’s Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)–infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV–1 and HSV–2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV–2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-ΔG/TT genotyping was determined by TaqMan. We compared women with IFNL4-ΔG/ΔG or IFNL4-TT/ΔG genotypes (i.e., IFNL4-ΔG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8% were positive for HSV–1 and 79.0% were positive for HSV–2. We observed no association between IFNL4-ΔG/TT genotype and any outcome: HSV–1 or HSV–2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV–2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV–2 DNA level (p = 0.68). In this large

  19. The Pavonia xanthogloea (Ekman, Malvaceae: Phenolic compounds quantification, anti-oxidant and cytotoxic effect on human lymphocytes cells

    Directory of Open Access Journals (Sweden)

    Clarice Pinheiro Mostardeiro

    2014-01-01

    Full Text Available Introduction: Pavonia xanthogloea is traditionally used as an antimicrobial and anti-tumour medicine in Southern Brazilian region. However, investigations about this species are still incipient. Hypothesis Tested: The study postulated that P. xanthologea specie present some phenolic compound and present some biological properties as anti-oxidant and cytoprotective effect against oxidative stress. Materials and Methods: The content of eight phenolic molecules in the crude ethanolic extract of the aerial part of P. xanthogloea and its five fractions (hexane, dichloromethane, ethyl-acetate, n-butanol, and water was determined by heterotrophic plate count method. The anti-oxidant capacity of the extract and the fractions was determined by 1,1-diphenyl-2-picryl-hydrazyl assay. The potential anti-oxidant and cytoprotective effect was also analyzed in human lymphocyte culture treated with extract/fractions at different concentrations with and without oxidative stress generated by hydrogen peroxide (H 2 O 2 and sodium nitroprusside (SNP exposition. Results: Tiliroside was the molecule detected in all extract. Water and ethyl-acetate fractions showed the highest radical-scavenging activity. The crude extract, hexane, water, and n-butanol reversed the higher reactive oxygen specie levels generated by H 2 O 2 and SNP to levels similar to those observed in the control group. In addition, crude extract, hexane, ethyl-acetate and n-butanol did not caused cytotoxicity, whereas water fraction was cytotoxic at higher concentration tested here (300 μg/mL. The cytotoxicity reversion caused by SNP exposition was concentration-dependent of the extract and fractions. However, dichloromethane fraction increased cell mortality in all concentrations investigated and was not able to decrease cell death in the lymphocytes exposed to SNP. Conclusion: The results suggest potential medicine use of this species.

  20. In vitro anti-telomerase activity of novel lycopene-loaded nanospheres in the human leukemia cell line K562

    Science.gov (United States)

    Gharib, Amir; Faezizadeh, Zohreh

    2014-01-01

    Background: Lycopene, a plant carotenoid, has potent effects against the various types of cancer cells. To date, the effect of lycopene in the free and encapsulated forms on the telomerase activity in human leukemia cell line K562 have not been investigated. The aim of the present study was to prepare a novel lycopene-loaded nanosphere and compare its anti-telomearse activity in K562 cell line with those of free lycopene. Materials and Methods: The lycopene-loaded nanospheres were prepared by nanoprecipitation method. The lycopene entrapment efficacy was measured by high-performance liquid chromatography (HPLC) method. The anti-proliferation effect of the lycopene in the free and encapsulated forms in the different times (0-72 h) and the different doses (0-100 μg/ml) on K562 cell line was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The changes of telomerase activity, following treatment with the lycopene in the free and encapsulated forms, were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay. Results: The entrapment efficacy of lycopene was 78.5% ± 2. Treatment of the K562 cell line with lycopene, in particular in encapsulated form, resulted in a significant inhibition of the cell growth and increasing of percentage of apoptotic cells. It has also been observed that the telomerase activity in the lycopene-loaded nanospheres-treated cells was significantly inhibited in a dose and time-dependent manner. Conclusion: Our data suggest a novel mechanism in the anti-cancer activity of the lycopene, in particular in encapsulated form, and could be provided a basis for the future development of anti-telomerase therapies. PMID:24914298

  1. Anti-Ro and anti-La autoantibodies induce TNF-α production by human salivary gland cells: an in vitro study

    Directory of Open Access Journals (Sweden)

    V. Mitolo

    2011-09-01

    Full Text Available Obiettivo: Lo scopo di questo studio è stato valutare la produzione di TNF-α, induttore della via estrinseca del processo apoptotico, in seguito al trattamento con gli autoanticorpi anti-Ro ed anti-La isolati da pazienti con sindrome di Sjögren primaria in un modello sperimentale rappresentato dalla linea cellulare di ghiandole salivari umane, A- 253. È stata, inoltre, valutata la presenza sulla superficie di tali cellule di recettori specifici per tale induttore, TNFR1 e TNFR2. Materiali e metodi: Gli autoanticorpi anti-La ed anti-Ro sono stati purificati su una colonna cromatografia ad alta affinità. Le metodiche utilizzate per la valutazione della produzione di TNF-α e lo studio dei recettori di superficie sono state immunofluorescenza, RT-PCR e saggi immunoenzimatici. Risultati: I nostri risultati hanno dimostrato che le cellule A-253 esprimono in superficie i recettori TNFR1 e TNFR2 e che gli autoanticorpi anti-Ro e anti-La sono in grado di indurre la produzione di TNF-α nelle stesse cellule. Conclusioni: Il trattamento con gli autoanticorpi anti-Ro ed anti-La induce la produzione di TNF-α in cellule di ghiandole salivari umane e questo potrebbe spiegare la attivazione della via estrinseca della apoptosi.

  2. Recombinant human immunoglobulin (Ig)A1 and IgA2 anti-D used for detection of IgA deficiency and anti-IgA

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Dziegiel, Morten Hanefeld

    2008-01-01

    To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA....

  3. Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

    Directory of Open Access Journals (Sweden)

    George J Cianciolo

    Full Text Available Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM proteins, termed the "immunosuppressive domain (ID", is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021 from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO(4-induced peritonitis. In vivo vasoprotective effects were determined using: (1 a carrageenan-induced model of disseminated intravascular coagulation (DIC in mice; (2 a reverse passive Arthus model in guinea pigs; and (3 vasoregulatory effects in spontaneously hypertensive rats (SHR. In vitro studies included: (1 binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC; (2 gene expression by RT-PCR of MN10021-treated VEC; and (3 apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-α. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10-15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase mRNA in VEC

  4. Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes

    Directory of Open Access Journals (Sweden)

    Alex I. Chernyavsky

    2014-01-01

    Full Text Available A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD.

  5. The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma

    Directory of Open Access Journals (Sweden)

    Yang Inchul

    2010-05-01

    Full Text Available Abstract Background Klotho was originally characterized as an anti-aging gene that predisposed Klotho-deficient mice to a premature aging-like syndrome. Recently, KLOTHO was reported to function as a secreted Wnt antagonist and as a tumor suppressor. Epigenetic gene silencing of secreted Wnt antagonists is considered a common event in a wide range of human malignancies. Abnormal activation of the canonical Wnt pathway due to epigenetic deregulation of Wnt antagonists is thought to play a crucial role in cervical tumorigenesis. In this study, we examined epigenetic silencing of KLOTHO in human cervical carcinoma. Results Loss of KLOTHO mRNA was observed in several cervical cancer cell lines and in invasive carcinoma samples, but not during the early, preinvasive phase of primary cervical tumorigenesis. KLOTHO mRNA was restored after treatment with either the DNA demethylating agent 2'-deoxy-5-azacytidine or histone deacetylase inhibitor trichostatin A. Methylation-specific PCR and bisulfite genomic sequencing analysis of the promoter region of KLOTHO revealed CpG hypermethylation in non-KLOTHO-expressing cervical cancer cell lines and in 41% (9/22 of invasive carcinoma cases. Histone deacetylation was also found to be the major epigenetic silencing mechanism for KLOTHO in the SiHa cell line. Ectopic expression of the secreted form of KLOTHO restored anti-Wnt signaling and anti-clonogenic activity in the CaSki cell line including decreased active β-catenin levels, suppression of T-cell factor/β-catenin target genes, such as c-MYC and CCND1, and inhibition of colony growth. Conclusions Epigenetic silencing of KLOTHO may occur during the late phase of cervical tumorigenesis, and consequent functional loss of KLOTHO as the secreted Wnt antagonist may contribute to aberrant activation of the canonical Wnt pathway in cervical carcinoma.

  6. The herpes simplex virus 1-encoded envelope glycoprotein B activates NF-κB through the Toll-like receptor 2 and MyD88/TRAF6-dependent signaling pathway.

    Directory of Open Access Journals (Sweden)

    Mingsheng Cai

    Full Text Available The innate immune response plays a critical role in the host defense against invading pathogens, and TLR2, a member of the Toll-like receptor (TLR family, has been implicated in the immune response and initiation of inflammatory cytokine secretion against several human viruses. Previous studies have demonstrated that infectious and ultraviolet-inactivated herpes simplex virus 1 (HSV-1 virions lead to the activation of nuclear factor kappa B (NF-κB and secretion of proinflammatory cytokines via TLR2. However, except for the envelope glycoprotein gH and gL, whether there are other determinants of HSV-1 responsible for TLR2 mediated biological effects is not known yet. Here, we demonstrated that the HSV-1-encoded envelope glycoprotein gB displays as molecular target recognized by TLR2. gB coimmunoprecipitated with TLR2, TLR1 and TLR6 in transfected and infected human embryonic kidney (HEK 293T cells. Treatment of TLR2-transfected HEK293T (HEK293T-TLR2 cells with purified gB results in the activation of NF-κB reporter, and this activation requires the recruitment of the adaptor molecules myeloid differentiation primary-response protein 88 (MyD88 and tumor necrosis factor receptor-associated factor 6 (TRAF6 but not CD14. Furthermore, activation of NF-κB was abrogated by anti-gB and anti-TLR2 blocking antibodies. In addition, the expression of interleukin-8 induced by gB was abrogated by the treatment of the human monocytic cell line THP-1 with anti-TLR2 blocking antibody or by the incubation of gB with anti-gB antibody. Taken together, these results indicate the importance and potency of HSV-1 gB as one of pathogen-associated molecular patterns (PAMPs molecule recognized by TLR2 with immediate kinetics.

  7. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    Science.gov (United States)

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer.

  8. A Novel Anti-Human Syndecan-1(CD138) Monoclonal Antibody 4B3: Characterization and Application

    Institute of Scientific and Technical Information of China (English)

    Wanping Sun; Fengming Wang; Fang Xie; Guoqing Wang; Jin Sun; Gehua Yu; Yuhua Qiu; Xueguang Zhang

    2007-01-01

    Syndecan-1 (CD138), a member of integral membrane heparin sulfate proteoglycans, is an essential matrix receptor for maintaining the normal morphological phenotypes. In this study, we generated a specific mouse anti-human syndecan-1 monoclonal antibody (mAb) 4B3 and identified it by competition assay with the available syndecan-1 mAb (BB4). Stained by 4B3, the expression of syndecan-1 was detected on tumor cell lines, such as 8226,U266, XG-1, XG-2, Daudi and Jurkat. The expression was also found on neuron stem cells. It was established that 4B3 mAb could inhibit XG-1 and XG-2 proliferation. The data not only determined that 4B3 mAb was a functional anti-human syndecan-1 mAb, but also indicated that syndecan-1 might be a valuable surface antigen and play an important role in regulation of tumor pathology and differentiation of neural stem cells. This novel antibody 4B3 may be value of study of tumor proliferation/survival mechanism and contributes to diagnosis and treatment of diverse diseases.

  9. Inhibitory Effects of Anti-sense PTTG on Malignant Phenotype of Human Ovarian Carcinoma Cell Line SK-OV-3

    Institute of Scientific and Technical Information of China (English)

    陈刚; 李静; 李辅军; 李箫; 周剑锋; 卢运萍; 马丁

    2004-01-01

    To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3. 1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3. 1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5 % and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3. 1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.

  10. Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice

    Institute of Scientific and Technical Information of China (English)

    Min-Hua Zheng; Bao-Ming Yu; Bo Feng; Jian-Wen Li; Ai-Guo Lu; Ming-Liang Wang; Wei-Guo Hu; Ji-Yuan Sun; Yan-Yan Hu; Jun-Jun Ma

    2005-01-01

    AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT.METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay.RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F= 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (χ2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups.CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer.The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

  11. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats.

    Science.gov (United States)

    Iznaga Escobar, N; Morales, A M; Ducongé, J; Torres, I C; Fernández, E; Gómez, J A

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t 1/2alpha) of 0.250 h and a mean elimination (t 1/2beta) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99mTc-labeled humanized MAb R3 conjugate in patients should be supported.

  12. Human platelet antigen (HPA)-1a peptides do not reliably suppress anti-HPA-1a responses using a humanized severe combined immunodeficiency (SCID) mouse model.

    Science.gov (United States)

    Jackson, D J; Eastlake, J L; Kumpel, B M

    2014-04-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs most frequently when human platelet antigen (HPA)-1a-positive fetal platelets are destroyed by maternal HPA-1a immunoglobulin (Ig)G antibodies. Pregnancies at risk are treated by administration of high-dose intravenous Ig (IVIG) to women, but this is expensive and often not well tolerated. Peptide immunotherapy may be effective for ameliorating some allergic and autoimmune diseases. The HPA-1a/1b polymorphism is Leu/Pro33 on β3 integrin (CD61), and the anti-HPA-1a response is restricted to HPA-1b1b and HLA-DRB3*0101-positive pregnant women with an HPA-1a-positive fetus. We investigated whether or not HPA-1a antigen-specific peptides that formed the T cell epitope could reduce IgG anti-HPA-1a responses, using a mouse model we had developed previously. Peripheral blood mononuclear cells (PBMC) in blood donations from HPA-1a-immunized women were injected intraperitoneally (i.p.) into severe combined immunodeficient (SCID) mice with peptides and HPA-1a-positive platelets. Human anti-HPA-1a in murine plasma was quantitated at intervals up to 15 weeks. HPA-1a-specific T cells in PBMC were identified by proliferation assays. Using PBMC of three donors who had little T cell reactivity to HPA-1a peptides in vitro, stimulation of anti-HPA-1a responses by these peptides occurred in vivo. However, with a second donation from one of these women which, uniquely, had high HPA-1a-specific T cell proliferation in vitro, marked suppression of the anti-HPA-1a response by HPA-1a peptides occurred in vivo. HPA-1a peptide immunotherapy in this model depended upon reactivation of HPA-1a T cell responses in the donor. For FNAIT, we suggest that administration of antigen-specific peptides to pregnant women might cause either enhancement or reduction of pathogenic antibodies.

  13. Downregulation of Cellular c-Jun N-Terminal Protein Kinase and NF-κB Activation by Berberine May Result in Inhibition of Herpes Simplex Virus Replication

    OpenAIRE

    Song, Siwei; Qiu, Min; Chu, Ying; Chen, Deyan; Wang, Xiaohui; Su, Airong; Wu, Zhiwei

    2014-01-01

    Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Some reports show that berberine exhibits anti-inflammatory, antitumor, and antiviral properties by modulating multiple cellular signaling pathways, including p53, nuclear factor κB (NF-κB), and mitogen-activated protein kinase. In the present study, we investigated the antiviral effect of berberine against herpes simplex virus (HSV) infection. Current antiherpes medicines such as acyclovir can le...

  14. Adenoviral-mediated delivery of herpes simplex virus thymidine kinase gene controlled by Cfos promoter confers cytotoxic effect on human glioma cells%腺病毒介导的HSV-TK/GCV系统在Cfos启动子调控下对胶质瘤细胞的杀伤作用

    Institute of Scientific and Technical Information of China (English)

    王浩; 潘建青; 胡继良; 冯诣; 宋伟健; 罗杰; 刘欣民; 魏强国; 洪全球

    2015-01-01

    目的 构建人Cfos启动子调控的单纯疱疹病毒(HSV)-胸苷激酶(TK)自杀基因重组腺病毒载体,观察其介导的HSV-TK/更昔洛韦(GCV)系统对胶质瘤细胞的杀伤作用. 方法 构建重组腺病毒载体Ad-Cfos-TK-IRES-hr绿色荧光蛋白(GFP)、Ad-CMV-TK-IRES-hrGFP,转染至HEK293细胞获得重组腺病毒Ad-Cfos-TK-IRES-hrGFP、Ad-CMV-TK-IRES-hrGFP,荧光计数法检测病毒滴度;将病毒感染U251、U87细胞,荧光显微镜下观察GFP的表达.将病毒感染U251、U87细胞,24 h后加入1000、100、10、1、0.1、0.01、0μmol/L GCV作用48 h,CCK-8法检测各组细胞抑制率. 结果 成功构建重组腺病毒载体pDC315-CMV-TK-IRES-hrGFP、pDC315-CFOS-TK-IRES-hrGFP.荧光计数法检测显示2种腺病毒滴度均达1×1010 PFU/mL.在病毒感染复数(MOI)为100、GCV浓度为1、10、100、1000 μmol/L时,转染Ad-Cfos-TK-IRES-hrGFP组U251细胞抑制率分别为(24.18±6.01)%、(30.39±9.67)%、(57.07±9.29)%、(94.50±3.48)%,转染Ad-Cfos-TK-IRES-hrGFP组U87细胞细胞抑制率分别为(9.78±2.24)%、(86.33±5.06)%、(98.48±0.79)%、(98.76±0.93)%. 结论 腺病毒介导的HSV-TK/GCV系统在Cfos启动子调控下在体外可以有效杀伤胶质瘤细胞.%Objective To construct recombinant adenovirus vectors containing herpes simple virus thymidine kinase (HSV-TK) controlled by human Cfos promoter and cytomegalovirus (CMV) promoter and observe the expression of adenovirus in human glioma U251 cells and their specific cytotoxic effect on U251 cells in combination with ganciclovir (GCV) in vitro.Methods Two recombinant adenovirus vectors containing herpes simplex virus thymidine kinase gene controlled by human Cfos promoter and CMV promoter were constructed (Ad-Cfos-TK-IRES-hr green fluorescent protein [GFP] and Ad-CMV-TK-IRES-hrGFP),respectively.For packaging virus,two adenovirus vectors were transfected into HEK293 cells.Ad-CMV-TK-IRES-hrGFP and Ad-Cfos-TK-IRES-hrGFP were collected,purified and

  15. Effect of the ionophore monensin on herpes simplex virus type 1-induced cell fusion, glycoprotein synthesis, and virion infectivity.

    Science.gov (United States)

    Kousoulas, K G; Bzik, D J; Person, S

    1983-01-01

    The ionophore monensin inhibited the formation of mature, fully glycosylated glycoproteins gB, gC, and gD during herpes simplex virus type 1 infection of human embryonic lung cells. Underglycosylated forms, including the apparent high-mannose precursor forms of the major glycoproteins, appeared. Monensin inhibited virus-induced cell fusion. Infectious virions produced in the presence of monensin appeared to contain predominantly underglycosylated glycoproteins. PMID:6307921

  16. A retrospective cohort analysis of the relationship between thyroid hormone level and herpes simplex virus-1 activation

    OpenAIRE

    Matthew Balish; Robert Freeman; Shao-Chung Victor Hsia; Jayesh Parmar

    2013-01-01

    A number of physiological factors have been suggested to participate in the Herpes Simplex Virus Type-1 (HSV-1) reactivation. Of particular interest is the effect of hormonal aberration on gene expression and activation. Thyroid hormone (TH) was shown to play a role in HSV-1 gene expression and replication in cell culture and animal models. We hypothesize that TH participates in the control of HSV latency and reactivation in humans by regulating viral gene expression and replication.

  17. Study on the relationship between cervix diseases and the infection of human papillomvirus, chulamydia trachomatis and herpes simplex virus Ⅱ%人乳头瘤病毒、沙眼衣原体和单纯疱疹病毒Ⅱ型感染与宫颈疾病的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李玲; 罗慧琴; 苗晋华

    2012-01-01

    目的 探讨人乳头瘤病毒(human papillomavirus,HPV)、沙眼衣原体(chlamydia trachomatis,CT)和单纯疱疹病毒Ⅱ型(herpes simplex virusⅡ,HSV-Ⅱ)感染与宫颈疾病的关系.方法 采用核酸分子快速杂交基因分型技术对598例宫颈脱落细胞进行HPV感染基因型分型测定,同时应用实时荧光定量PCR法(FQ-PCR)检测CT和HSV-Ⅱ两种病原体的感染情况.结果 HPV、CT和HSV-Ⅱ的阳性检出率分别为24.9%、9.2%和8.9%,且随着宫颈病变程度加重而逐渐增高,宫颈炎组和宫颈癌病变组三种病原体的感染率差异均有统计学意义.HPV感染以高危型为主(占77.9%),低危型为22.1%.HPV高危型和阴性组比较两种病毒的感染率有统计学差异(CT:x2=26.97,P<0.05;HSV-Ⅱ∶x2=65.93,P<0.05).各宫颈病变组均有多病毒混合感染情况出现,其中宫颈癌组混合感染率为22.2%.结论 HPV、CT和HSV-Ⅱ感染与宫颈癌的发生密切相关,多病原体混合感染会促进宫颈癌的发生.%Objective To investigate the relationship between cervix diseases and the infection of human papillomavirus (HPV),chlamydia trachomatis (CT) and herpes simplex virus Ⅱ (HSV Ⅱ).Methods DNA flow-through hybridization genotyping technique was used to detect HPV infection genotyping from 598 patients with cervix infection,and FQ-PCR was applied to determine the infection of CT and HSV Ⅱ.Results The positive rate of HPV,CT and HSV Ⅱ was 24.9%,9.2% and 8.9%,respectively.The positive rates of HPV,CT and HSV Ⅱ were gradually increased according to the severity of cervix diseases.The differences of infection rate were statistically significant between cervicitis group and cervical cancer lesions group.HR-HPV were detected in 77.9% of HPV positive samples,and the positive rate of LR-HPV was 22.1%.The positive rates of CT and HSV Ⅱ were significantly different among HR-HPV group and HPV negative group (CT:x2 =26.97,P < 0.05 ; HSV-Ⅱ:x2 =65.93,P <0

  18. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S;

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  19. Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival

    DEFF Research Database (Denmark)

    Singh, Ripudaman; Kølvraa, Steen; Bross, Peter Gerd;

    2010-01-01

    A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longe...

  20. Quantification of Ethanol's Anti-Punishment Effect in Humans Using the Generalized Matching Equation

    Science.gov (United States)

    Rasmussen, Erin B.; Newland, M. Christopher

    2009-01-01

    Increases in rates of punished behavior by the administration of drugs with anxiolytic effects (called antipunishment effects) are well established in animals but not humans. The present study examined antipunishment effects of ethanol in humans using a choice procedure. The behavior of 5 participants was placed under six concurrent…

  1. Immunogenicity screening assay development for a novel human-mouse chimeric anti-CD147 monoclonal antibody (Metuzumab).

    Science.gov (United States)

    Mi, Li; Li, Wei; Li, Maohua; Chen, Tao; Wang, Muyang; Sun, Le; Chen, Zhinan

    2016-06-01

    The clinical effect of patient immune responses to therapeutic antibodies affect product safety and efficacy, which makes the development of valid, sensitive immune assays a key aspect of antibody drug development. In this paper, we reported the generations of mouse monoclonal and Cynomolgus monkey polyclonal antibodies against the anti-CD147 antibody (Metuzumab) as the internal standards and the positive controls. Seven mouse monoclonal antibodies were shown to recognize both (Fab)2 and full length of Metuzumab, but not the control normal human IgGs, and monoclonal anti-Metuzumab, Clone 2D9 was chosen to be used as the internal standard for anti-Metuzumab study. A Bridging ELISA assay was developed by coating the wells with the antibody drug, and the anti-drug antibody (ADA) in the animal sera were detected by enzyme-labeled antibody. Its limit of detection (LOD) was determined to be 0.39ng/ml of anti-Metuzumab antibody (ADA) with linear range between 0.39-50ng/ml and R(2)=0.994. For normal monkey sera, a minimal dilution was determined to be 1:80. However, very different from peptide or other protein drugs, strong interferences from the residual antibody drugs were observed from most of the testing monkey sera in the preclinical study. It was experimentally determined that the concentration of the residual antibody drug in the assay have to be lower than 1μg/ml, so the assays were carried out at 1:100 dilution of the monkey sera. In the pre-clinical study, 32 monkeys were treated with escalating doses of Metuzumab between 0, 10, 50, 200mg/kg for 13 times over 13weeks of time period. 16 of them were terminated right after the last injection, while the other 16 were rested for additional 4weeks before termination. Afraid to miss any positive response to antibody drug, sera samples were collected at six time points, including 2-, 6- and 10-weeks post 1st dose, prior to last dose, and 2-, 4-weeks into recovery. The highest positive rates were seen with the Medium

  2. Relationship of Epstein-Barr virus and human herpes virus-6 to chronic periodontitis%慢性牙周炎与爱泼斯坦-巴尔病毒和人疱疹病毒6型的相关性

    Institute of Scientific and Technical Information of China (English)

    缪羽; 张晓敏

    2012-01-01

    慢性牙周炎是一种最常见的多因素、炎症性和破坏性疾病,其发病与微生物、宿主和环境等多种因素有关,但其发病机制至今不明.研究显示,疱疹病毒与慢性牙周炎的发生发展有一定的相关性.爱泼斯坦-巴尔病毒(EBV)、人疱疹病毒(HHV)-6型均属疱疹病毒,本文就EBV、HHV-6以及二者间的关系,EBV和HHV-6引发慢性牙周炎的相关机制,EBV与慢性牙周炎,HHV-6与慢性牙周炎等研究进展作一综述.%Chronic periodontitis is the most common periodontal disease, a multi factor, inflammatory and destructive disease. Its incidence is related with microbial, host and environmental factors and so on. But its patho-genesis has not been fully resolved. For the past few years, most reasearches found that there were some relationship between herpesvirus and many varieties of periodontitis. Epstein-Barr virus(EBV) and human herpes virus(HHV)-6 belong to the herpesvirus. The review will introduce the relationship between EBV and HHV-6. The mechanism of EBV and HHV-6 caused chronic periodontitis, the relationship of EBV and chronic periodontitis, HHV-6 and chronic periodontitis and other studies.

  3. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

    Science.gov (United States)

    Suarez, Eloah Rabello; Chang, De-Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J.; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A.

    2016-01-01

    Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen. PMID:27145284

  4. Hepatitis B or hepatitis C co-infection in individuals infected with human immunodeficiency virus and effect of anti-tuberculosis drugs on liver function

    OpenAIRE

    Padmapriyadarsini C; Chandrabose J; Victor L; Hanna L; Arunkumar N; Swaminathan Soumya

    2006-01-01

    Background: Tuberculosis (TB) and hepatitis are the two common co-infections in patients infected with human immunodeficiency virus (HIV). Anti-tuberculosis treatment (ATT) may have an effect on the liver enzymes in these co-infected HIV patients. Aims: To determine the prevalence of Hepatitis B and C virus coinfection in HIV infected patients in Tamilnadu and assess effects of anti-tuberculosis drugs on their liver function. Settings: HIV positive subjects referred to the Tuberculosis R...

  5. Anti-inflammatory functions of purpurogallin in LPS-activated human endothelial cells

    Directory of Open Access Journals (Sweden)

    Tae Hoon Kim

    2012-03-01

    Full Text Available Enzymatic oxidation of commercially available pyrogallol wasefficiently transformed to an oxidative product, purpurogallin.Purpurogallin plays an important role in inhibiting glutathioneS-transferase, xanthine oxidase, catechol O-methyltransferaseactivities and is effective in the cell protection of several celltypes. However, the anti-inflammatory functions of purpurogallinare not well studied. Here, we determined the effectsof purpurogallin on lipopolysaccharide (LPS-mediated proinflammatoryresponses. The results showed that purpurogallininhibited LPS-mediated barrier hyper-permeability, monocyteadhesion and migration and such inhibitory effects weresignificantly correlated with the inhibitory functions ofpurpurogallin on LPS-mediated cell adhesion molecules(vascular cell adhesion molecules, intracellular cell adhesionmolecule, E-selectin. Furthermore, LPS-mediated nuclearfactor-κB (NF-κB and tumor necrosis factor-α (TNF-α releasesfrom HUVECs were inhibited by purpurogallin. Given theseresults, purpurogallin showed its anti-inflammatory activitiesand could be a candidate as a therapeutic agent for varioussystemic inflammatory diseases. [BMB reports 2012; 45(3:200-205

  6. Comparison of six human anti-transglutaminase ELISA-tests in the diagnosis of celiac disease in the Saharawi population

    Institute of Scientific and Technical Information of China (English)

    Eloy Fernández; Sabino Riestra; Luis Rodrigo; Carlos Blanco; Antonio López-Vázquez; Dolores Fuentes; Maria Moreno; Carlos López-Larrea

    2005-01-01

    AIM: Celiac disease (CD) is an enteropathic disorder very prevalent in Seharawi people. Our aim was to investigate the diagnostic accuracy of six human tissue transglutaminase (tTG) based ELISA tests in Saharawi CD patients.METHODS: Fifty-two CD patients and 23 controls were selected from the Saharawi refugee camps in Tinduf. CD patients were divided into two groups according to their anti-endomysium (EmA) status: 41 EmA positive and 11 EmA negative. Sera from patients and controls were tested for human tTG using six commercial ELISA kits. We used receiver operating characteristics (ROC) curves and areas under the curve to compare the diagnostic accuracies of the six assays.RESULTS: In general, there are differences in the sensitivity and specificity of the human tTG ELISA assays used. Diagnostic accuracy of tests was significantly improved by adjusting the cut-off thresholds according to ROC plot analysis; the correction of the cut-off with the employment of the ROC curve analysis modifies the decision limit in more than 50% in five of the six kits evaluated.CONCLUSION: Some of the human tTG ELISAs used in this study have a diagnostic accuracy similar to EmA determination for diagnosis of CD in Saharawi people. However, it is necessary to select the assay with a higher sensitivity and specificity, and recalculate the cut-off threshold using samples from the referral population.

  7. Activation of the human nuclear xenobiotic receptor PXR by the reverse transcriptase-targeted anti-HIV drug PNU-142721

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yuan; Redinbo, Matthew R. (UNC)

    2012-10-09

    The human pregnane X receptor (PXR) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. PXR responds to a structurally diverse variety of endogenous and xenobiotic compounds, and coordinates the expression of genes central to the metabolism and excretion of potentially harmful chemicals, including human therapeutics. The reverse transcriptase inhibitor PNU-142721 has been designed to treat human immunodeficiency virus (HIV) infection. Although this compound has anti-HIV activity, it was established using cell-based assays that PNU-142721 is an efficacious PXR agonist. We present here the 2.8 {angstrom} resolution crystal structure of the human PXR ligand-binding domain in complex with PNU-142721. PXR employs one hydrogen bond and fourteen van der Waals contacts to interact with the ligand, but allows two loops adjacent to the ligand-binding pocket to remain disordered in the structure. These observations highlight the role structural flexibility plays in PXR's promiscuous responses to xenobiotics. The crystal structure also explains why PNU-173575, a thiomethyl metabolite of PNU-142721, exhibits enhanced PXR activation relative to the unmodified compound and why PNU-142721 can also activate rat PXR. Taken together, the results presented here elucidate the structural basis for PXR activation by PNU-142721 and related chemicals.

  8. Biodistribution and γ imaging of 125I-labeled goat anti-human IgG polyclonal antibody in nude mice bearing human colon cancer xenografts

    International Nuclear Information System (INIS)

    The possibility of IgG secreted from tumor cells as a target for radioimmunoimaging and targeted therapy of cancers were investigated. Goat anti-human IgG polyclonal anti- body (GAHG) was radioiodinated using Iodogen method, and the in vitro stability and pharmacokinetics were evaluated. The biodistribution and γ imaging of 125I-GAHG were performed in nude mice bearing HT-29 human colon cancer xenografts. 125I-GAHG showed good in vitro stability, and its blood clearance was defined as a two-compartment model, with T1/2α and T1/2β were 1.19 h and 43.99 h, respectively. The tumor uptake of 125I-GAHG was higher than that of 125I-labeled normal goat IgG control (125I-GIgG). 125I-GAHG showed good tumor retention when injecting via intra-tumor. In the biodistribution study, the highest tumor uptake of 125I-GAHG was 6.71±2.19%ID/g at 72 h postinjection and the T/NT increased along with the postinjection time. The results show that 125I-GAHG have good tumor-specific uptake which may provide a novel idea for radioimmunoimaging and targeted therapy of cancers. (authors)

  9. Herpes simplex virus glycoprotein C: molecular mimicry of complement regulatory proteins by a viral protein.

    Science.gov (United States)

    Huemer, H P; Wang, Y; Garred, P; Koistinen, V; Oppermann, S

    1993-08-01

    Herpes simplex virus (HSV) encodes a protein, glycoprotein C (gC), which binds to the third complement component, the central mediator of complement activation. In this study the structural and functional relationships of gC from HSV type 1 (HSV-1) and known human complement regulatory proteins factor H, properdin, factor B, complement receptor 1 (CR1) and 2 (CR2) were investigated. The interaction of gC with C3b was studied using purified complement components, synthetic peptides, antisera against different C3 fragments and anti-C3 monoclonal antibodies (mAb) with known inhibitory effects on C3-ligand interactions. All the mAb that inhibited gC/C3b interactions, in a differential manner, also prevented binding of C3 fragments to factors H, B, CR1 or CR2. No blocking was observed with synthetic peptides representing different C3 regions or with factor B and C3d, whereas C3b, C3c and factor H were inhibitory, as well as purified gC. There was no binding of gC to cobra venom factor (CVF), a C3c-like fragment derived from cobra gland. Purified gC bound to iC3, iC3b and C3c, but failed to bind to C3d. Glycoprotein C bound only weakly to iC3 derived from bovine and porcine plasma, thus indicating a preference of the viral protein for the appropriate host. Binding of gC was also observed to proteolytic C3 fragments, especially to the beta-chain, thus suggesting the importance of the C3 region as a binding site. Purified gC from HSV-1, but not HSV-2, inhibited the binding of factor H and properdin but not of CR1 to C3b. The binding of iC3b to CR2, a molecule involved in B-cell activation and binding of the Epstein-Barr virus, was also inhibited by the HSV-1 protein. As factor H and properdin, the binding of which was inhibited by gC, are important regulators of the alternative complement pathway, these data further support a role of gC in the evasion of HSV from a major first-line host defence mechanism, i.e. the complement system. In addition, the inhibition of the C3/CR

  10. Macrophages and cytokines in the early defence against herpes simplex virus

    Directory of Open Access Journals (Sweden)

    Ellermann-Eriksen Svend

    2005-08-01

    Full Text Available Abstract Herpes simplex virus (HSV type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites

  11. Anti-tumor Effect and Its Mechanisms of Ursolic Acid on Human Esophageal Carcinoma Cell Eca-109 in Vivo

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-qing; SHEN Yi; DUANG Hong

    2008-01-01

    Objective:To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo.Methods:A transplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established.40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid(25-100 mg·kg-1.d-1)was injected into abdominal cavity respectively once everyday and lasted for fourteen days.The changes of tumor volume were measured continuously and tumor inhibition rate was calculated.The morphological changes of apoptosis were observed by electron microscope.The expressions of COX-2,bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry.At last the PGE2 level of transplanted tumors was detected by radioimmunoassay.Results:Treatment of nude mice with 25,50,or 100 mg·kg-1.d-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses.The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups,while the Bax increased.The PGE2 level of transplanted tumors was decreased in ursolic acid groups with a dose-related manner.Conclusion:Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo,which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.

  12. Antiviral activity of salivary microRNAs for ophthalmic herpes zoster

    Directory of Open Access Journals (Sweden)

    Irmak M

    2012-06-01

    Full Text Available Abstract Ophthalmic herpes zoster is a common ocular infection caused by the varicella-zoster virus (VZV. Viral mRNA transcripts play a major role in the replicative cycle of the virus and current antiviral agents have little effect in preventing and treating the complications. Therapeutic use of saliva for certain painful ocular diseases such as ophthalmic herpes zoster is a well-known public practice in our region. We thought that antiviral activity of saliva may stem from salivary microvesicles and we aimed to look for molecules with antiviral activity in these vesicles. As a possible candidate for antiviral activity, salivary microvesicles contain at least 20 microRNAs (miRNAs, small noncoding RNAs, which suppress the translation of target mRNAs. miRNAs not only participate in maintenance of normal cell functions, but are also involved in host–virus interactions and limit the replication of certain virus types. Thus, miRNA gene therapy by targeting mRNAs required for VZV survival may find a niche in the treatment of ophthalmic herpes zoster. But, how could salivary microvesicles reach into the corneal cells to demonstrate their antiviral activity. We suggest that human salivary microvesicles can be effective carriers of miRNA for corneal cells, because they contain a molecular machinery for vesicle trafficking and fusion allowing them to be endocytosed by target cells. After binding to the plasma membrane, microvesicles seem to enter into the corneal cells through the clathrin-mediated endocytosis. In the cytosol, human salivary miRNAs base-pair with specific viral mRNAs and inhibit their translation, thus limiting the replication of the virus.

  13. Cold Sore, Cold Soul? An Examination of Orolabial Herpes in Film

    OpenAIRE

    Holliday, Alex C.; Salih, Amanda; Wagner, Richard F.Jr.

    2014-01-01

    [EN] The sociocultural phenomenon of herpes is attributed to two strains of the herpes simplex virus: herpes simplex virus type 1 (HSV-1) causes orolabial cold sores while herpes simplex virus type 2 (HSV-2) is typically identified in genital lesions, though both viruses may cause clinically similar signs and symptoms anywhere in or on the body. While these infections are extremely prevalent and typically benign, media sources such as film have perpetuated a negative public percep...

  14. Control of STDs--the role of prophylactic vaccines against herpes simplex virus

    OpenAIRE

    Stanberry, L R

    1998-01-01

    OBJECTIVES: To summarise the current status of genital herpes simplex virus (HSV) vaccine development and provide a discussion of the potential benefits and limitations of genital herpes vaccines. METHODS: Literature review. RESULTS: Genital herpes simplex virus infection has a complex pathogenesis that has contributed to it becoming a serious worldwide problem. In an attempt to control the problem five different types of genital herpes vaccines have been developed. These include inacti...

  15. Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year old boy

    OpenAIRE

    Regina Eziuka Oladokun; Olomukoro, Chikodili N; Owa, Adewale B.

    2013-01-01

    Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age...

  16. Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action

    Science.gov (United States)

    Ceña-Diez, Rafael; Vacas-Córdoba, Enrique; García-Broncano, Pilar; de la Mata, FJ; Gómez, Rafael; Maly, Marek; Muñoz-Fernández, Mª Ángeles

    2016-01-01

    Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3-S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3-S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH–gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2-S16, providing a step forward to prevent HSV-2 transmission in humans. PMID:27274240

  17. Herpes simplex virus type-1(HSV-1 oncolytic and highly fusogenic mutants carrying the NV1020 genomic deletion effectively inhibit primary and metastatic tumors in mice

    Directory of Open Access Journals (Sweden)

    David Andrew T

    2008-06-01

    Full Text Available Abstract Background The NV1020 oncolytic herpes simplex virus type-1 has shown significant promise for the treatment of many different types of tumors in experimental animal models and human trials. Previously, we described the construction and use of the NV1020-like virus OncSyn to treat human breast tumors implanted in nude mice. The syncytial mutation gKsyn1 (Ala-to-Val at position 40 was introduced into the OncSyn viral genome cloned into a bacterial artificial chromosome using double-red mutagenesis in E. coli to produce the OncdSyn virus carrying syncytial mutations in both gB(syn3 and gK(syn1. Results The OncdSyn virus caused extensive virus-induced cell fusion in cell culture. The oncolytic potential of the OncSyn and OncdSyn viruses was tested in the highly metastatic syngeneic mouse model system, which utilizes 4T1 murine mammary cancer cells implanted within the interscapular region of Balb/c mice. Mice were given three consecutive intratumor injections of OncSyn, OncdSyn, or phosphate buffered saline four days apart. Both OncSyn and OncdSyn virus injections resulted in significant reduction of tumor sizes (p Conclusion These results show that the attenuated, but highly fusogenic OncSyn and OncdSyn viruses can effectively reduce primary and metastatic breast tumors in immuncompetent mice. The available bac-cloned OncSyn and OncdSyn viral genomes can be rapidly modified to express a number of different anti-tumor and immunomodulatory genes that can further enhance their anti-tumor potency.

  18. Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T lymphocytes to extracellular matrix proteins.

    Science.gov (United States)

    Tomer, Y; Lider, O; Gilburd, B; Hershkoviz, R; Meroni, P L; Wiik, A; Shoenfeld, Y

    1997-06-01

    Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can activate neutrophils to adhere to endothelium, degranulate, and cause endothelial cell injury. These data have lead to the hypothesis that the T cell inflammatory response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to stimulation of neutrophils by ANCA. So far there is no evidence for a direct effect of ANCA on lymphocytes. The present study was designed to examine whether lymphocytes can be directly stimulated by ANCA to adhere to endothelial extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes to fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG containing ANCA or control human IgG, respectively; P = 0.0045). The same induction of adhesion to fibronectin, laminin, and intact ECM was observed when the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG. Similarly, ANCA-enriched IgG produced in mice increased the adhesion of lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endothelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to ECM. PMID:9175913

  19. Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

    OpenAIRE

    Broze, G J; S. Hickman; Miletich, J P

    1985-01-01

    Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

  20. Expression of the HNK-1 carbohydrate epitope in human retina and retinoblastoma. An immunohistochemical study with the anti-Leu-7 monoclonal antibody.

    OpenAIRE

    KivelÀ, Tero Tapani

    1986-01-01

    Fifty formalin-fixed and paraffin-embedded retinoblastoma specimens and five normal human eyes were studied with the monoclonal anti-Leu-7 antibody, directed against the HNK-1 carbohydrate epitope that is shared by human natural killer cells and many neuronal, glial and neuroectodermal cells. The laboratory method was a sensitive immunohistochemical staining procedure, and neuroectodermal tumours that usually express this epitope were used as positive controls. In the human retina, MÃŒller ce...

  1. Human semen contains exosomes with potent anti-HIV-1 activity

    OpenAIRE

    Madison, Marisa N; Roller, Richard J.; Okeoma, Chioma M.

    2014-01-01

    Background Exosomes are membranous nanovesicles secreted into the extracellular milieu by diverse cell types. Exosomes facilitate intercellular communication, modulate cellular pheno/genotype, and regulate microbial pathogenesis. Although human semen contains exosomes, their role in regulating infection with viruses that are sexually transmitted remains unknown. In this study, we used semen exosomes purified from healthy human donors to evaluate the role of exosomes on the infectivity of diff...

  2. Goat anti-rabbit IgG conjugated fluorescent dye-doped silica nanoparticles for human breast carcinoma cell recognition.

    Science.gov (United States)

    Chen, Min-Yan; Chen, Ze-Zhong; Wu, Ling-Ling; Tang, Hong-Wu; Pang, Dai-Wen

    2013-11-12

    We report an indirect method for cancer cell recognition using photostable fluorescent silica nanoprobes as biological labels. The dye-doped fluorescent silica nanoparticles were synthesized using the water-in-oil (W/O) reverse microemulsion method. The silica matrix was produced by the controlled hydrolysis of tetraethylorthosilicate (TEOS) in water nanodroplets with the initiation of ammonia (NH3·H2O). Fluorescein isothiocyanate (FITC) or rhodamine B isothiocyanate conjugated with dextran (RBITC-Dextran) was doped in silica nanoparticles (NPs) with a size of 60 ± 5 nm as a fluorescent signal element by covalent bonding and steric hindrance, respectively. The secondary antibody, goat anti-rabbit IgG, was conjugated on the surface of the PEG-terminated modified FITC-doped or RBITC-Dextran-doped silica nanoparticles (PFSiNPs or PBSiNPs) by covalent binding to the PEG linkers using the cyanogen bromide method. The concentrations of goat anti-rabbit IgG covering the nanoprobes were quantified via the Bradford method. In the proof-of-concept experiment, an epithelial cell adhesion molecule (EpCAM) on the human breast cancer SK-Br-3 cell surface was used as the tumor marker, and the nanoparticle functionalized with rabbit anti-EpCAM antibody was employed as the nanoprobe for cancer cell recognition. Compared with fluorescent dye labeled IgG (FITC-IgG and RBITC-IgG), the designed nanoprobes display dramatically increased stability of fluorescence as well as photostability under continuous irradiation. PMID:24179992

  3. Detection of erythropoiesis-stimulating agents in human anti-doping control: past, present and future.

    Science.gov (United States)

    Leuenberger, Nicolas; Reichel, Christian; Lasne, Françoise

    2012-07-01

    Stimulation of erythropoiesis is one of the most efficient ways of doping. This type of doping is advantageous for aerobic physical exercise and of particular interest to endurance athletes. Erythropoiesis, which takes place in bone marrow, is under the control of EPO, a hormone secreted primarily by the kidneys when the arterial oxygen tension decreases. In certain pathological disorders, such as chronic renal failure, the production of EPO is insufficient and results in anemia. The pharmaceutical industry has, thus, been very interested in developing drugs that stimulate erythropoiesis. With this aim, various strategies have been, and continue to be, envisaged, giving rise to an expanding range of drugs that are good candidates for doping. Anti-doping control has had to deal with this situation by developing appropriate methods for their detection. This article presents an overview of both the drugs and the corresponding methods of detection, and thus follows a roughly chronological order. PMID:22831473

  4. 快速诊断发热出疹婴幼儿疱疹病毒6型活动感染的研究%Study on fast diagnostics of activated infection of human herpes virus type 6 in infants with fever and rash

    Institute of Scientific and Technical Information of China (English)

    孙荷; 吉川哲史

    2010-01-01

    目的 探讨分别用共聚焦显微镜和荧光显微镜观测疱疹病毒6型(hman herpes virus type 6,HHV-6)早期抗原(IEA)的检测结果,快速诊断发热出疹婴幼儿HHV-6活动感染.方法 采集临床2岁以下发热出疹婴幼儿末梢静脉血55例,在采血当日,用间接免疫荧光法,以HHV-6 IEA/ex3兔单克降抗体,检测患儿单核细胞中的HHV-6 IEA,使用共聚焦显微镜观测结果.同时进行患儿单核细胞HHV-6病毒分离.其中44例患儿单核细胞与脐血细胞混合培养48 h再进行HHV-6 IEA检测,用普通荧光显微镜观测结果.结果 共聚焦显微镜观测采血当日HHV-6 IEA结果与病毒分离结果的符合率达92.73%,敏感度90.32%,特异度95.83%.细胞培养48 h普通荧光显微镜观测结果与病毒分离结果符合率为87.50%,敏感度77.27%,特异度100%.结论 用共聚焦显微镜在采血当日观测HHV-6 IEA,及患儿单核细胞与脐血细胞混合培养48 h用荧光显微镜观测HHV-6 IEA,可以协助临床快速诊断发热出疹婴幼儿HHV-6活动性感染.%Objective To explore the fast diagnostics of activated infection of human herpes virus type 6 (HHV-6) with IEA/ex3( an antibody specific for an immediate early protein encoded by variant B HHV-6 U90 gene)in infants with fever and rash . Methods To collect the 55 samples of peripheral blood mononuclear cells (PBMCs) from clinical infants whose having a fever and rash, age are below 2 years old.The immediate early antigen (IEA) of HHV-6 were analyzed with IEA/ex3 in PBMCs by indirect immunofluorescence then using confocal microscope to observe, and using fluoromicroscope to observe after the PBMCs of 44 samples were incubated with cord blood cell at 37℃ in a humidified 5% CO2 atmosphere for 48 hours. The virus was isolated from the PBMCs. Results The conformation rate of the HHV-6 IEA using confocal microscope to observe and virus isolation was 92.73%, sensitivity was 90.32%, specificity was 95.83% and it was respectively 87

  5. Herpes Zoster in Healthy Children: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Birgül Tepe

    2016-06-01

    Full Text Available Objective: Herpes zoster is an acute dermatomal viral infection caused by the reactivation of varicella zoster virus. While it is commonly seen among elderly and immunocompromised individuals, it is rare in healthy children. The aim of this study was to evaluate the clinical features, treatment and complications of healthy children with herpes zoster. Methods: Thirty one patients aged between 0-16 years who were admitted to our clinic with the diagnosis of herpes zoster, between January 2014 and December 2014, were evaluated retrospectively for age, gender, month of admission, complaint, history of chickenpox infection or varicella vaccination, triggering factors, dermatomal involvement, complications and treatment. Results: Among 31 patients with diagnosis of herpes zoster, 19 were boys (61.3% and 12 were girls (38.7%. The mean of age was 9.12±4.4 years. Twenty patients had thoracic (64.5%, six had lumbar (19.4% and five had cervical involvements (16.2%. The most frequent symptoms were pruritus and pain, respectively. Six patients were administered topical treatment and 25 patients were treated with both systemic and topical treatments. Complication was not observed. Conclusion: Herpes zoster is also being encountered increasingly in healthy children nowadays. It is benign and generally no complications are observed. Incidence can vary because of geographic and socioeconomic differences like vaccination programs.

  6. Herpes zoster: A clinical study in 205 patients

    Directory of Open Access Journals (Sweden)

    E N Abdul Latheef

    2011-01-01

    Full Text Available Background: Even though herpes zoster is a common condition its incidence and pattern of occurrence in the era of HIV disease is significant. Aim: To analyze the incidence, pattern of occurrence and evolution of herpes zoster with special attention to provocative factors if any. Materials and Method s: This was an analytical study conducted for 2 years based on a preformed proforma containing preliminary information, a detailed clinical evaluation regarding the segment of involvement, morphology, pattern of lesions, complications, disseminations etc. and investigations to establish provocative factors if any. Results: Incidence of herpes zoster was mainly in the fourth and third decades of life. A definite history of chicken pox was present in only 63.4% cases. In the majority (70% herpes zoster occurred spontaneously. In 30% cases, immunosuppression due to chemotherapy, malignancy, HIV infection, diabetes mellitus were observed. The commonest segment affected was thoracic (42.4% followed by cranial (28.2% and cervical (12.1%. Majority resolved in 7-14 days except immunosuppressed. 34.6% of the patients had complications such as secondary bacterial infection, post herpetic neuralgia, and motor weakness. Ten patients had HIV infection as a provocative factor. Conclusion: The results of incidence and clinical pattern of herpes zoster is almost parallel to the previous studies. Any factors of immunosuppression should be checked, especially HIV, particularly in disseminated and long-lasting cases.

  7. Charles Bonnet syndrome after herpes simplex encephalitis.

    Science.gov (United States)

    Aydin, Ömer Faruk; Ince, Hülya; Taşdemir, Haydar Ali; Özyürek, Hamit

    2012-04-01

    Visual impairment associated with Charles Bonnet syndrome is rarely reported in childhood. We describe a child who presented with visual hallucinations and postinfectious bilateral retrobulbar optic neuritis. The patient had undergone acyclovir therapy for 3 weeks because of herpes encephalitis. Four days after therapy was completed, he experienced visual impairment in both eyes. He manifested a bilateral decrease in visual acuity, with normal funduscopic findings. The patient experienced visual hallucinations for about 1 week, and then experienced total loss of vision. During his hallucinations, the patient did not exhibit behavioral changes or cognitive impairment. The visual hallucinations included unfamiliar children hiding under his bed, and he spoke to someone whom he did not know. Magnetic resonance imaging indicated bilateral optic nerve hyperintensity on T(2)-weighted and contrast-enhanced images. The patient received corticosteroid therapy for his retrobulbar optic neuritis, and his vision returned to normal after 1 month. Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome.

  8. Anti-hepatocarcinoma Effects of a Food Additive Chrysin Nanosuspension against Human HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Zhi-ping Wang

    2015-03-01

    Full Text Available Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Chrysin (Chr, a major symbol ingredient in Chinese Propolis, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Chr-Nanosuspension (Chr-NS composed of Chr and poloxamer 188 was prepared by high pressure homogenization technique. The in vitro anti-hepatocarcinoma effects of Chr-NS relative to efficacy of bulk Chr were evaluated. The particle size and zeta potential of Chr-NS were 291.1 nm and -28.7 mV, respectively. MTT assay showed that Chr-NS effectively inhibited the proliferation of HepG2 cells and the corresponding IC50 values of Chr-NS and bulk Chr were 1.55 and 3.76 &mug/mL. These results suggest that the delivery of Chr-NS is a promising approach for treating tumors.

  9. Anti-Hepatocarcinoma Effects of a Food Additive Resveratrol Nanosuspension against Human HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Shi-Qiong Luo

    2015-05-01

    Full Text Available Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Resveratrol (Res, a major symbol ingredient in red grapes and peanuts, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Res-nanosuspension (Res-NS composed of Res and poloxamer 188 was prepared by high pressure homogenization technique. The in vitro anti-hepatocarcinoma effects of Res-NS relative to efficacy of bulk Res were evaluated. The particle size and zeta potential of Res-NS were 159.4 nm and -22.1 mV, respectively. MTT assay showed that Res-NS effectively inhibited the proliferation of HepG2 cells and the corresponding IC50 values of Res-NS and bulk Res were 2.91 and 7.13 &mug/mL. These results suggest that the delivery of Res-NS is a promising approach for treating tumors.

  10. Downregulation of amplified in breast cancer 1 contributes to the anti-tumor effects of sorafenib on human hepatocellular carcinoma

    Science.gov (United States)

    Dan, Yuzhen; Tong, Zhangwei; Chen, Wenbo; Qin, Liping; Liu, Kun; Li, Wengang; Mo, Pingli; Yu, Chundong

    2016-01-01

    Multi-kinase inhibitor sorafenib represents a major breakthrough in the therapy of advanced hepatocellular carcinoma (HCC). Amplified in breast cancer 1 (AIB1) is frequently overexpressed in human HCC tissues and promotes HCC progression. In this study, we investigated the effects of sorafenib on AIB1 expression and the role of AIB1 in anti-tumor effects of sorafenib. We found that sorafenib downregulated AIB1 protein expression by inhibiting AIB1 mRNA translation through simultaneously blocking eIF4E and mTOR/p70S6K/RP-S6 signaling. Knockdown of AIB1 significantly promoted sorafenib-induced cell death, whereas overexpression of AIB1 substantially diminished sorafenib-induced cell death. Downregulation of AIB1 contributed to sorafenib-induced cell death at least in part through upregulating the levels of reactive oxygen species in HCC cells. In addition, resistance to sorafenib-induced downregulation of AIB1 protein contributes to the acquired resistance of HCC cells to sorafenib-induced cell death. Collectively, our study implicates that AIB1 is a molecular target of sorafenib and downregulation of AIB1 contributes to the anti-tumor effects of sorafenib. PMID:27105488

  11. Several Human Cyclin-Dependent Kinase Inhibitors, Structurally Related to Roscovitine, As New Anti-Malarial Agents

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    Sandrine Houzé

    2014-09-01

    Full Text Available In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs. Among newly proposed anti-malaria targets, are the P. falciparum cyclin-dependent kinases (PfCDKs. There are involved in different stages of the protozoan growth and development but share high sequence homology with human cyclin-dependent kinases (CDKs. We previously reported the synthesis of CDKs inhibitors that are structurally-related to (R-roscovitine, a 2,6,9-trisubstituted purine, and they showed activity against neuronal diseases and cancers. In this report, we describe the synthesis and the characterization of new CDK inhibitors, active in reducing the in vitro growth of P. falciparum (3D7 and 7G8 strains. Six compounds are more potent inhibitors than roscovitine, and three exhibited IC50 values close to 1 µM for both 3D7 and 7G8 strains. Although, such molecules do inhibit P. falciparum growth, they require further studies to improve their selectivity for PfCDKs.

  12. Anti-proliferative effect of leaf extracts of Eucalyptus citriodora against human cancer cells in vitro and in vivo.

    Science.gov (United States)

    Bhagat, Madhulika; Sharma, Vikas; Saxena, Ajit Kumar

    2012-12-01

    Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of Ehrlich ascites carcinoma and Sarcoma 180. The results showed that ethyl acetate and aqueous extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%, respectively). The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which has shown significant in vitro and in vivo anticancer potential. PMID:23350280

  13. Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen Burkholderia pseudomallei K96243.

    Directory of Open Access Journals (Sweden)

    Andrea J Dowling

    Full Text Available Burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. The bacterium is endemic to tropical regions, including South East Asia and Northern Australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages. However despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterized to date. Here we perform a genome-wide gain of function screen of B. pseudomallei strain K96243 to identify loci encoding factors with anti-macrophage activity. We identify a total of 113 such loci scattered across both chromosomes, with positive gene clusters encoding transporters and secretion systems, enzymes/toxins, secondary metabolite, biofilm, adhesion and signal response related factors. Further phenotypic analysis of four of these regions shows that the encoded factors cause striking cellular phenotypes relevant to infection biology, including apoptosis, formation of actin 'tails' and multi-nucleation within treated macrophages. The detailed analysis of the remaining host of loci will facilitate genetic dissection of the interaction of this important pathogen with host macrophages and thus further elucidate this critical part of its infection cycle.

  14. Associations of HLA-A, HLA-B and HLA-C Alleles Frequency with Prevalence of Herpes Simplex Virus Infections and Diseases Across Global Populations: Implication for the Development of an Universal CD8+ T-Cell Epitope-Based Vaccine

    Science.gov (United States)

    Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S.; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A.; Lemonnier, François A.; BenMohamed, Lbachir

    2014-01-01

    A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) Over half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A*24, HLA-B*27, HLA-B*53 and HLA-B*58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B*44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. PMID:24798939

  15. Experimental studies on the prevention and treatment of chickenpox and herpes zoster with measles vaccine.

    Science.gov (United States)

    Li, W H; Ming, Z L; Chen, Q; Li, Y

    1989-05-01

    In 151 chickenpox patients treated with live attenuated measles vaccine, the cure rate was 100%. In 145 cases of herpes zoster, the effective rate was 100% (completely cured in 91.7% and improved in 8.3%). In the treated group, the time needed for the subsidence of fever and skin rash and the duration of the disease were markedly shorter than those in the control group (P less than 0.01). It is particularly effective for alleviating pain, preventing and relieving postherpetic neuralgia in patients with zoster. The application of measles vaccine to the patients in the chickenpox incubation period might prevent the development of the disease, and decrease the incidence and death rate of varicella zoster virus infection in highly susceptible patients. The mechanism of its anti-viral action and production of interferon in the body is discussed.

  16. Antiviral activity of the volatile oils of Melissa officinalis L. against Herpes simplex virus type-2.

    Science.gov (United States)

    Allahverdiyev, A; Duran, N; Ozguven, M; Koltas, S

    2004-11-01

    Melissa officinalis L. (Lamiaceae) has been used in a variety of practical applications in medical science. Our objective in the current study was to determine the effects of the volatile oil components of M. officinalis on Herpes simplex virus type 2 (HSV-2) replication in HEp-2 cells. Four different concentrations (25, 50, 100, 150 and 200 microg/ml) of volatile oils were examined. Experiments were carried out using HEp-2 cells. M. officinalis volatile oil was found to be non-toxic to HEp-2 cells up to a concentration of 100 micro/ml. It was, however, found to be slightly toxic at a concentration over of 100 microg/ml. The antiviral activity of non-toxic concentrations against HSV-2 was tested. The replication of HSV-2 was inhibited, indicating that the M. officinalis L. extract contains an anti-HSV-2 substance. PMID:15636181

  17. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers.

    Science.gov (United States)

    Paolino, Donatella; Lucania, Giuseppe; Mardente, Domenico; Alhaique, Franco; Fresta, Massimo

    2005-08-18

    The aim of this work was the evaluation of various ethosomal suspensions made up of water, phospholipids and ethanol at various concentrations for their potential application in dermal administration of ammonium glycyrrhizinate, a useful drug for the treatment of various inflammatory-based skin diseases. Physicochemical characterization of ethosomes was carried out by photon correlation spectroscopy and freeze fracture electron microscopy. The percutaneous permeation of ammonium glycyrrhizinate/ethosomes was evaluated in vitro through human stratum corneum and epidermis membranes by using Franz's cells and compared with the permeation profiles of drug solutions either in water or in a water-ethanol mixture. Reflectance spectrophotometry was used as a non-invasive technique to evaluate the carrier toxicity, the drug permeation and the anti-inflammatory activity of ammonium glycyrrhizinate in a model of skin erythema in vivo on human volunteers. Ethosomal suspensions had mean sizes ranging from 350 nm to 100 nm as a function of ethanol and lecithin quantities, i.e., high amounts of ethanol and a low lecithin concentration provided ethosome suspensions with a mean size of approximately 100 nm and a narrow size distribution. In vitro and in vivo experiments were carried out by using an ethosome formulation made up of ethanol 45% (v/v) and lecithin 2% (w/v). The ethosome suspension showed a very good skin tolerability in human volunteers, also when applied for a long period (48 h). Ethosomes elicited an increase of the in vitro percutaneous permeation of both methylnicotinate and ammonium glycyrrhizinate. Ethosomes were able to significantly enhance the anti-inflammatory activity of ammonium glycyrrhizinate compared to the ethanolic or aqueous solutions of this drug. Some in vivo experiments also showed the ability of ethosome to ensure a skin accumulation and a sustained release of the ammonium glycyrrhizinate.

  18. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers.

    Science.gov (United States)

    Paolino, Donatella; Lucania, Giuseppe; Mardente, Domenico; Alhaique, Franco; Fresta, Massimo

    2005-08-18

    The aim of this work was the evaluation of various ethosomal suspensions made up of water, phospholipids and ethanol at various concentrations for their potential application in dermal administration of ammonium glycyrrhizinate, a useful drug for the treatment of various inflammatory-based skin diseases. Physicochemical characterization of ethosomes was carried out by photon correlation spectroscopy and freeze fracture electron microscopy. The percutaneous permeation of ammonium glycyrrhizinate/ethosomes was evaluated in vitro through human stratum corneum and epidermis membranes by using Franz's cells and compared with the permeation profiles of drug solutions either in water or in a water-ethanol mixture. Reflectance spectrophotometry was used as a non-invasive technique to evaluate the carrier toxicity, the drug permeation and the anti-inflammatory activity of ammonium glycyrrhizinate in a model of skin erythema in vivo on human volunteers. Ethosomal suspensions had mean sizes ranging from 350 nm to 100 nm as a function of ethanol and lecithin quantities, i.e., high amounts of ethanol and a low lecithin concentration provided ethosome suspensions with a mean size of approximately 100 nm and a narrow size distribution. In vitro and in vivo experiments were carried out by using an ethosome formulation made up of ethanol 45% (v/v) and lecithin 2% (w/v). The ethosome suspension showed a very good skin tolerability in human volunteers, also when applied for a long period (48 h). Ethosomes elicited an increase of the in vitro percutaneous permeation of both methylnicotinate and ammonium glycyrrhizinate. Ethosomes were able to significantly enhance the anti-inflammatory activity of ammonium glycyrrhizinate compared to the ethanolic or aqueous solutions of this drug. Some in vivo experiments also showed the ability of ethosome to ensure a skin accumulation and a sustained release of the ammonium glycyrrhizinate. PMID:15935505

  19. An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal model Imunofluorescência para diagnóstico de herpes oftálmico usando como modelo córneas de camundongos infectados

    Directory of Open Access Journals (Sweden)

    Sílvia Regina Ferreira Gonçalves Pereira

    2007-04-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 ophthalmic disease is the most common cause of corneal blindness in humans world-wide. Current culture techniques for HSV take several days and commercially available HSV laboratory based diagnostic techniques vary in sensitivity. Our study was conducted to evaluate the use of a quicker and simpler method to herpes ophthalmic diagnosis. Corneal smears were made by firm imprints of infected mouse eyes to glass slides, after smears were fixated with cold acetone, and an indirect immunofluorescence (IIF method was performed using monoclonal antibodies in a murine model of ophthalmic herpes. Eye swabs from infected mice were inoculated in Vero cells for virus isolation. Cytology and histology of the eye were also performed, using hematoxylin-eosin routine. Mouse eyes were examined by slit-lamp biomicroscopy for evidence of herpetic disease at various times postinoculation. We made a comparative evaluation of sensitivity, specificity and speed of methods for laboratory detection of HSV. Our results indicate that this IIF method is quick, sensitive, specific and can be useful in the diagnosis of ophthalmic herpes as demonstrated in an animal model.A doença oftálmica do vírus herpes simplex do tipo 1 (HSV-1 é a causa mais comum de cegueira córnea em humanos mundialmente. Técnicas de cultura atuais para HSV levam vários dias e laboratórios de HSV comercialmente disponíveis estabelecem que as técnicas diagnósticas variam em sensibilidade. Nosso estudo foi conduzido para avaliar a aplicação prática de um método mais rápido e simples para diagnosticar o herpes oftálmico. Decalques córneos foram feitos por impressões firmes de olhos de camundongos a lâminas de vidro, depois os decalques foram fixados com acetona fria, e um método de imunofluorescência indireta (IIF foi executado empregando anticorpos monoclonais no modelo murino de herpes oftálmico. Swabs de córnea foram inoculados em células Vero

  20. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.

    Science.gov (United States)

    Scapin, Giovanna; Yang, Xiaoyu; Prosise, Winifred W; McCoy, Mark; Reichert, Paul; Johnston, Jennifer M; Kashi, Ramesh S; Strickland, Corey

    2015-12-01

    Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. We speculate that this new conformation is driven by the shorter hinge. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility.

  1. Cloning, Eukaryotic Expression of Human ISG20 and Preliminary Study on the Effect of Its Anti-HBV

    Institute of Scientific and Technical Information of China (English)

    Youhua HAO; Dongliang YANG

    2008-01-01

    Human ISG20 gene was cloned and the effect of its anti-HBV was primarily studied. The ISG20 gene was amplified from HeLa cells by RT-PCR and recombinant vector expressing ISG20 was constructed by genetic engineering. The overexpression of ISG20 in HepG2 cells was detected by Western blot and the levels of secretion of HBs antigen and HBe antigen tested by ELISA. The results showed that: (1) Sequence of ISG20 cloned was consistent to that published in Genebank; (2) Recombinant vector expressing ISG20 could be expressed in HepG2 cells by transfection; (3) The overexpression of ISG20 protein could reduce the levels of the secretion of HBs antigen and HBe an-tigen in transfected HepG2 cells. It was suggested that the overexpression of recombinant ISG20 in culture cells could reduce the synthesis of HBV proteins.

  2. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  3. Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation.

    Science.gov (United States)

    Fuchs, Christiane; Rosner, Margit; Dolznig, Helmut; Mikula, Mario; Kramer, Nina; Hengstschläger, Markus

    2012-03-01

    Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products.

  4. A Novel Murine Anti-Lactoferrin Monoclonal Antibody Activates Human Polymorphonuclear Leukocytes through Membrane-Bound Lactoferrin and TLR4

    Directory of Open Access Journals (Sweden)

    Xiao-Min Hu

    2015-01-01

    Full Text Available Soluble lactoferrin (LTF is a versatile molecule that not only regulates the iron homeostasis, but also harbors direct microbicidal and immunomodulating abilities in mammalian body fluids. In contrast, little is known about the function of membrane-bound LTF (mbLTF, although its expression on human polymorphonuclear leukocytes (huPMNs has been reported for decades. Given that LTF/anti-LTF antibodies represent a potential diagnostic/prognostic biomarker and a therapeutic target in patients with immune disorders, we wished, in the present study, to generate a novel human LTF- (huLTF- specific mAb suitable for detailed analyses on the expression and function of mbLTF as well as for deciphering the underlying mechanisms. By using the traditional hybridoma cell fusion technology, we obtained a murine IgG1 (kappa mAb, M-860, against huLTF. M-860 recognizes a conformational epitope of huLTF as it binds to natural, but not denatured, huLTF in ELISA. Moreover, M-860 detects mbLTF by FACS and captures endogenous huLTF in total cell lysates of huPMNs. Functionally, M-860 induces the activation of huPMNs partially through TLR4 but independently of phagocytosis. M-860 is thus a powerful tool to analyze the expression and function of human mbLTF, which will further our understanding of the roles of LTF in health and disease.

  5. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells.

    Science.gov (United States)

    Bancos, Simona; Bernard, Matthew P; Topham, David J; Phipps, Richard P

    2009-01-01

    The widely used non-steroidal anti-inflammatory drugs (NSAIDs) function mainly through inhibition of cyclooxygenases 1 and 2 (Cox-1 and Cox-2). Unlike Cox-1, Cox-2 is considered an inducible and pro-inflammatory enzyme. We previously reported that Cox-2 is upregulated in activated human B lymphocytes and using Cox-2 selective inhibitors that Cox-2 is required for optimal antibody synthesis. It is not known whether commonly used non-prescription and non-Cox-2 selective drugs also influence antibody synthesis. Herein, we tested a variety of Cox-1/Cox-2 non-selective NSAIDs, namely ibuprofen, tylenol, aspirin and naproxen and report that they blunt IgM and IgG synthesis in stimulated human peripheral blood mononuclear cells (PBMC). Ibuprofen had its most profound effects in inhibiting human PBMCs and purified B lymphocyte IgM and IgG synthesis when administered in the first few days after activation. As shown by viability assays, ibuprofen did not kill B cells. The implications of this research are that the use of widely available NSAIDs after infection or vaccination may lower host defense. This may be especially true for the elderly who respond poorly to vaccines and heavily use NSAIDs.

  6. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  7. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna;

    2015-01-01

    85 antimetabolites that can inhibit growth of, or even kill, any of the cell lines, while at the same time not being toxic for 83 different healthy human cell types. 60 of these antimetabolites were found to inhibit growth in all cell lines. Finally, we experimentally validated one of the predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies.......Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...

  8. Perspectives and limits of an immunoenzymatic assay (ELISA) for herpes simplex virus (HSV) tumor-associated antigen (TAA).

    Science.gov (United States)

    Tarro, G; D'Alessandro, G; Esposito, C; Flaminio, G; Mascolo, A; Maturo, S

    1981-01-01

    An ELISA has been developed to detect specific antibodies for HSV-TAA in sera of patients with head, neck and urogenital tract carcinomas (Cancer, 45:1980). Further studies have shown that 64/800 controls (8.12%), i.e. healthy people, are positive against 312/425 patients with herpes associated tumors (73.41%). People with herpes recurrens show 18% positivity, precancerous lesions 44% and other cancers 6%. Immunodepression, chemo- and radio-therapy play an inhibitory role on the ELISA positivity for TAA. Radical surgery of the HSV-TAA positive cancers results in lack of specific antibody whereas relapse or metastasis of the tumor yields positive results. The reproducibility of the test is very good and the standard error is low (1.0655). The conclusions allow us to foresee the use of this ELISA for early detection of the HSV-TAA antibodies in certain human carcinomas.

  9. Cross-reactive anti-viral T cells increase prior to an episode of viral reactivation post human lung transplantation.

    Directory of Open Access Journals (Sweden)

    Thi H O Nguyen

    Full Text Available Human Cytomegalovirus (CMV reactivation continues to influence lung transplant outcomes. Cross-reactivity of anti-viral memory T cells against donor human leukocyte antigens (HLA may be a contributing factor. We identified cross-reactive HLA-A*02:01-restricted CMV-specific cytotoxic T lymphocytes (CTL co-recognizing the NLVPMVATV (NLV epitope and HLA-B27. NLV-specific CD8+ T cells were expanded for 13 days from 14 HLA-A*02:01/CMV seropositive healthy donors and 11 lung transplant recipients (LTR then assessed for the production of IFN-γ and CD107a expression in response to 19 cell lines expressing either single HLA-A or -B class I molecules. In one healthy individual, we observed functional and proliferative cross-reactivity in response to B*27:05 alloantigen, representing approximately 5% of the NLV-specific CTL population. Similar patterns were also observed in one LTR receiving a B27 allograft, revealing that the cross-reactive NLV-specific CTL gradually increased (days 13-193 post-transplant before a CMV reactivation event (day 270 and reduced to basal levels following viral clearance (day 909. Lung function remained stable with no acute rejection episodes being reported up to 3 years post-transplant. Individualized immunological monitoring of cross-reactive anti-viral T cells will provide further insights into their effects on the allograft and an opportunity to predict sub-clinical CMV reactivation events and immunopathological complications.

  10. Anti-Tumor Effect of Curcumin on Human Cervical Carcinoma HeLa Cells In Vitro and In Vivo

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jing; ZHAO Yong; ZHANG Yan; CHEN Wei

    2007-01-01

    Objective: To investigate the anti-tumor effect of curcumin on human cervical carcinoma HeLa cells in vitro and in vivo. Methods: (1) Human cervical carcinoma cell line HeLa was cultured in vitro. HeLa cells were treated with 5-50μmol/L curcumin for 24. 48, 72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy and flow cytometry (FCM). (2) A transplanted tumor model by injecting HeLa cells into subcutaneous tissue of BABL/C mice was established and its growth curve was measured. 30 BABL/C mice with tumors were divided into 2 groups at random and 0.2 ml saline or 0.2 ml 250 μmol/L curcumin was injected into abdominal cavity respectively once everyday and lasted for ten days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. At last the expressions of caspase-3 and bax protein in transplanted tumors were detected by immunohistochemistry. Results: (1) Curcumin inhibited the proliferation of Lela cells on a dose-depending manner. Apoptosis of cells could be observed by FCM. Partial cells presented the characteristic morphological changes of apoptosis under electron microseope. (2) When 1×107 HeLa cells were inoculated for each mouse, 100% of the mice developed growing tumors after seven days. An inhibition effect was observed in treatment group, and the inhibition rate of curcumin was 74.33%. The expressions of caspase-3 and bax in the transplanted tumors were increased in curcumin group. Conclusion: Curcumin is effective as an anti-cancer drug not only in vitro but also in vivo.

  11. Herpes zoster of trigeminal nerve after dental extraction

    Directory of Open Access Journals (Sweden)

    Nagappa Guttiganur

    2013-01-01

    Full Text Available Herpes zoster is an uncommon acute viral infection caused by reactivation of varicella zoster virus. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist. Practicing dentist may carry out emergency treatment that might result in irreversible damage or may delay the appropriate treatment. With an ever-increasing number of elderly and immunocompromised patients reporting to the dentist, the dental profession can expect to encounter an increased number of herpes zoster patients. Dentist must be familiar with the presenting signs and symptoms of patients experiencing the prodromal manifestations of herpes zoster of the trigeminal nerve. This article focuses on the difficulties in management of such cases, and one such case is reported here.

  12. Recurrent herpes zoster in a child with SLE

    Directory of Open Access Journals (Sweden)

    Jain C

    1995-01-01

    Full Text Available A 12-year-old girl had systemic lupus erythematosus (SLE and type IV lupus nephritis since three-and-a-half years. She was treated with prednisolone and cyclophosphamide. She had first attack of herpes zoster (HZ involving eighth and ninth thoracic segments on right side at the age of nine years. Second attack occurred on the same segments on same side at the age of twelve years. The second attack of herpes zoster was treated with oral acyclovir 400 mg five times a day for seven days plus analgesics and multi-vitamins. Most probably this is the first case of recurrent herpes zoster (RHZ in a child in Indian literature.

  13. Isolated, complete paralytic mydriasis secondary to herpes zoster ophthalmicus.

    Science.gov (United States)

    Czyz, Craig N; Bacon, Thomas S; Petrie, Thomas P; Justice, Joshua D; Cahill, Kenneth V

    2013-06-01

    Herpes zoster ophthalmicus is a manifestation of herpes zoster when the ophthalmic division of the trigeminal nerve becomes involved. Ocular symptoms are varied and mainly due to inflammatory mechanisms. Total, external and/or internal ophthalmoplegias, as well as isolated third, fourth and sixth cranial nerve palsies have all been reported as complications. In a minority of cases, concurrent pupillary paralysis has been documented. The presentation of complete paralytic mydriasis as the sole cranial nerve complication following herpes zoster ophthalmicus infection is a rare finding. The postulated pathophysiologic aetiology is a partial third nerve palsy with the pupillary fibres for light and accommodation-convergence affected and motor fibres spared. The mechanism responsible for the postulated lesion is speculative.

  14. Reactivity of eleven anti-human leucocyte monoclonal antibodies with lymphocytes from several domestic animals

    DEFF Research Database (Denmark)

    Aasted, Bent; Blixenkrone-Møller, Merete; Larsen, Else Bang;

    1988-01-01

    Nine commercially available monoclonal antibodies and two monoclonal antibodies from The American Type Culture Collection, raised against various human leucocyte surface antigens, were tested on lymphocytes from cow, sheep, goat, swine, horse, cat, dog, mink, and rabbit as well as man. Four...

  15. Preparation and functional studies of hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody

    Directory of Open Access Journals (Sweden)

    Yang J

    2014-05-01

    Full Text Available Jingjing Yang,1,3,* Xiaoping Huang,1,3,* Fanghong Luo,1 Xiaofeng Cheng,3 Lianna Cheng,3 Bin Liu,4 Lihong Chen,2 Ruyi Hu,1,3 Chunyan Shi,1,3 Guohong Zhuang,1,3 Ping Yin2 1Anti-Cancer Research Center, Medical College, Xiamen University, Fujian, People's Republic of China, 2The Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, People's Republic of China, 3Organ transplantation institution, Xiamen University, Xiamen, People's Republic of China, 4Jilin Vocational College of Industry and Technology, Jilin, People's Republic of China  *These authors contributed equally to this work Objective: To prepare hydroxyethyl chitosan nanoparticles loaded with anti-human death receptor 5 single-chain antibody, and study their characteristics, functions, and mechanisms of action. Materials and methods: The anti-human death receptor 5 single-chain antibody was constructed and expressed. Protein-loaded hydroxyethyl chitosan nanoparticles were prepared, and their size, morphology, particle-size distribution and surface zeta potential were measured by scanning electron microscopy and laser particle-size analysis. Mouse H22 hepatocellular carcinoma cells were cultured, and growth inhibition was examined using the CellTiter-Blue cell-viability assay. Flow cytometry and Hoechst 33342 were employed to measure cell apoptosis. Kunming mice with H22 tumor models were treated with protein-loaded hydroxyethyl chitosan nanoparticles, and their body weight and tumor size were measured, while hematoxylin and eosin staining was used to detect antitumor effects in vivo and side effects from tumors. Results: The protein-loaded hydroxyethyl chitosan nanoparticles had good stability; the zeta potential was -24.2±0.205, and the dispersion index was 0.203. The inhibition of the protein-loaded hydroxyethyl chitosan nanoparticles on H22 growth was both time- and dose-dependent. Increased expressions of active caspase 8, active caspase 3, and BAX were detected

  16. Role of Bacterial Exopolysaccharides as Agents in Counteracting Immune Disorders Induced by Herpes Virus

    Directory of Open Access Journals (Sweden)

    Concetta Gugliandolo

    2015-08-01

    Full Text Available Extreme marine environments, such as the submarine shallow vents of the Eolian Islands (Italy, offer an almost unexplored source of microorganisms producing unexploited and promising biomolecules for pharmaceutical applications. Thermophilic and thermotolerant bacilli isolated from Eolian vents are able to produce exopolysaccharides (EPSs with antiviral and immunomodulatory effects against Herpes simplex virus type 2 (HSV-2. HSV-2 is responsible for the most common and continuously increasing viral infections in humans. Due to the appearance of resistance to the available treatments, new biomolecules exhibiting different mechanisms of action could provide novel agents for treating viral infections. The EPSs hinder the HSV-2 replication in human peripheral blood mononuclear cells (PBMC but not in WISH (Wistar Institute Susan Hayflic cells line, indicating that cell-mediated immunity was involved in the antiviral activity. High levels of Th1-type cytokines were detected in PBMC treated with all EPSs, while Th2-type cytokines were not induced. These EPSs are water soluble exopolymers able to stimulate the immune response and thus contribute to the antiviral immune defense, acting as immunomodulators. As stimulants of Th1 cell-mediated immunity, they could lead to the development of novel drugs as alternative in the treatment of herpes virus infections, as well as in immunocompromised host.

  17. Anti-bacterial effects of the essential oil of Teucrium polium L. on human pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammad

    2013-09-01

    Results: The total oil content of Teucrium polium plant was 0.75%. Twenty eight compounds were identified in the essential oil that included 99.75% of the total oil. The major components were α-pinene (12.52%, Linalool (10.63% and Caryophyllene oxide (9.69%. For study of antimicrobial activity of the oil sample, the essential oil was tested against 9 bacteria by disc diffusion method. The antimicrobial effects of this essential oil was determined against three Gram positive bacteria Staphylococcus areous (PTCC 1431, Staphylococcus epidermidis (PTCC 1436, Streptococcus faecalis (PTCC 1237; as well as six Gram negative bacteria Pseudomonas aeroginosa (PTCC 11430, Shigella flexneri (PTCC 1716, Kellebsiella pneuomonae(PTCC=1053, Salmonella typhi (PTCC=1609, Serratia marcescens (PTCC 1187 and Escherichia coli (PTCC 1533. The antimicrobial effects of this essential oil on the Gram positive bacteria ( Staphylococcus aureus and Staphylococcus epidermidis and on all the Gram negative bacteria tested was much higher than those observed by tetracycline. Conclusions: The results showed the essential oil of Teucrium polium had strong anti-bacterial effects. The relatively high contents of α-pinene and Linalool in the essential oil may be the cause of its potential medicinal effects

  18. Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Evgeny Shmelkov

    Full Text Available The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs. Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design.

  19. IMMUNE INHIBITION OF VIRUS RELEASE FROM HUMAN AND NONHUMAN CELLS BY ANTIBODY TO VIRAL AND HOST-CELL DETERMINANTS

    NARCIS (Netherlands)

    SHARIFF, DM; DESPERBASQUES, M; BILLSTROM, M; GEERLIGS, HJ; WELLING, GW; WELLINGWESTER, S; BUCHAN, A; SKINNER, GRB

    1991-01-01

    Immune inhibition of release of the DNA virues, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and su

  20. Humanization and characterization of an anti-ricin neutralization monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Wei-Gang Hu

    Full Text Available Ricin is regarded as a high terrorist risk for the public due to its high toxicity and ease of production. Currently, there is no therapeutic or vaccine available against ricin. D9, a murine monoclonal antibody developed previously in our laboratory, can strongly neutralize ricin and is therefore a good candidate for humanization. Humanization of D9 variable regions was achieved by a complementarity-determining region grafting approach. The humanized D9 (hD9 variable regions were further grafted onto human heavy and light chain constant regions to assemble the complete antibody gene. A foot-and-mouth-disease virus-derived 2A self-processing sequence was introduced between heavy and light chain DNA sequences to cleave the recombinant protein into a functional full-length antibody molecule from a single open reading frame driven by a single promoter in an adenoviral vector. After expression in mammalian cells and purification, the hD9 was demonstrated to have equimolar expression of the full-length antibody heavy and light chains. More importantly, the hD9 exhibited high affinity to ricin with K(D of 1.63 nM, comparable to its parental murine D9 (2.55 nM. In a mouse model, intraperitoneal (i.p. administration of hD9, at a low dose of 5 µg per mouse, 4 hours after the i.p. challenge with 5×LD50 ricin was found to rescue 100% of the mice. In addition, administered 6 hours post-challenge, hD9 could still rescue 50% of the mice. The hD9 has the potential to be used for prophylactic or therapeutic purposes against ricin poisoning.

  1. Anti-Aging Potential of Phytoextract Loaded-Pharmaceutical Creams for Human Skin Cell Longetivity

    OpenAIRE

    Saima Jadoon; Sabiha Karim; Muhammad Hassham Hassan Bin Asad; Muhammad Rouf Akram; Abida Kalsoom Khan; Arif Malik; Chunye Chen; Ghulam Murtaza

    2015-01-01

    The exposure to ultraviolet radiations (UVR) is the key source of skin sunburn; it may produce harmful entities, reactive oxygen species (ROS), leading to aging. The skin can be treated and protected from the injurious effects of ROS by using various pharmaceutical formulations, such as cream. Cream can be loaded with antioxidants to quench ROS leading to photo-protective effects. Moreover, modern medicines depend on ethnobotanicals for protection or treatment of human diseases. This review a...

  2. Thermodynamic study on the interaction between anti-tumor drug tegafur and human serum albumin

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The changes of thermodynamic properties of the system on interaction between tegafur and human serum albumin (HSA) and the changes of secondary structure units of HSA in the system at 298.15 K have been investigated by the Nano-Watt-Scale isothermal titration calorimetry (ITC), the Langmuirs binding model and the circular dichroism (CD) spectrometry.(C) 2007 Lin Wei Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  3. A Human-Animal-Robot Cooperative System for Anti-Personal Mine Detection

    OpenAIRE

    Nanayakkara, Thrishantha; Dissanayake, Tharindu; Mahipala, Prasanna; Sanjaya, K. A. Gayan

    2008-01-01

    To the best of the author's knowledge, this is the first time a human-robot-animal integrated system is tested for antipersonnel landmine detection. The proposed system tries to integrate distinct capabilities of three different systems to improve the effectiveness of landmine detection in a cluttered environment. The mongoose is found to be a rodent with extremely sensitive olfactory capabilities, dexterous navigation capabilities in a cluttered environment, and small enough to burrow throug...

  4. Cloning and Sequence Analysis of Light Variable Region Gene of Anti-human Retinoblastoma Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Zhong; Yongping Li; Shuqi Huang; Bo Ning; Chunyan Zhang; Jianliang Zheng; Guanguang Feng

    2002-01-01

    Purpose: To clone the variable region gene of light chain of monoclonal antibody against human retinoblastoma and to analyze the characterization of its nucleotide sequence as well as amino acid sequence.Methods: Total RNA was extracted from 3C6 hybridoma cells secreting specific monoclonal antibody(McAb)against human retinoblastoma(RB), then transcripted reversely into cDNA with olig-dT primers.The variable region of the light chain (VL) gene fragments was amplified using polymeerase chain reaction(PCR) and further cloned into pGEM(R) -T Easy vector. Then, 3C6 VL cDNA was sequenced by Sanger's method.Homologous analysis was done by NCBI BLAST.Results: The complete nucleotide sequence of 3C6 VL cDNA consisted of 321 bp encoding 107 amino acid residues, containing four workframe regions(FRs)and three complementarity-determining regions (CDRs) as well as the typical structure of two cys residues. The sequence is most homological to a member of the Vk9 gene family, and its chain utilizes the Jkl gene segment.Conclusion: The light chain variable region gene of the McAb against human RB was amplified successfully , which belongs to the Vk9 gene family and utilizes Vk-Jk1 gene rearrangement. This study lays a good basis for constructing a recombinant antibody and for making a new targeted therapeutic agents against retinoblastoma.

  5. Zinc is an antioxidant and anti-inflammatory agent: Its role in human health

    Directory of Open Access Journals (Sweden)

    Ananda S Prasad

    2014-09-01

    Full Text Available Zinc supplementation trials in the elderly showed that the incidence of infections was decreased by approximately 66% in the zinc group. Zinc supplementation also decreased oxidative stress biomarkers and decreased inflammatory cytokines in the elderly. In our studies in the experimental model of zinc deficiency in humans, we showed that zinc deficiency per se increased the generation of IL-1β and its mRNA in human mononuclear cells following LPS stimulation. Zinc supplementation upregulated A20, a zinc transcription factor, which inhibited the activation of NF-κB, resulting in decreased generation of inflammatory cytokines. Oxidative stress and chronic inflammation are important contributing factors for several chronic diseases attributed to aging, such as atherosclerosis and related cardiac disorders, cancer, neurodegeneration, immunologic disorders and the aging process itself. Zinc is very effective in decreasing reactive oxygen species (ROS. In this review, the mechanism of zinc actions on oxidative stress and generation of inflammatory cytokines and its impact on health in humans will be presented.

  6. Clinical relationship between human herpes virus and human papilloma virus infections and paranasal sinuses inverted papilloma%疱疹病毒及人乳头状瘤病毒感染与鼻窦内翻性乳头状瘤的临床关系

    Institute of Scientific and Technical Information of China (English)

    孙彦珍; 袁征; 李珍; 张子杰; 王晶璇

    2016-01-01

    OBJECTIVE To explore the prevalence of human herpes virus (EBV) and human papilloma virus (HPV) infections in patients with nose ,paranasal sinuses inverted papilloma so as to understand the role of EBV and HPV in the nose ,paranasal sinuses inverted papilloma .METHODS A total of 40 patients with nose ,paranasal sinuses inverted papilloma who were treated in the hospital from Jun 2013 to Jun 2015 were recruited as the study objects . The EBV and HPV in the nose ,paranasal sinuses papilloma paraffin-embedded tissues were detected by using pol-ymerase-chain-reaction assay .Totally 40 patients with nose ,paranasal sinuses inverted papilloma were assigned as the experimental group ,including 10 cases of papilloma malignancy and 30 cases of nose ,paranasal sinuses invert-ed papilloma .Totally 20 patients with nasal polyps were chosen as the control group .RESULTS The HPV was tested positive in 27 cases of the experimental group ,with the positive rate 67 .5% ;the EBV was tested positive in 17 cases of the experimental group ,with the positive rate 42 .5% ;the positive rates of HPV and EBV were signif-icantly higher in the experimental group than in the control group (P< 0 .05) .Of the 30 patients with nose ,para-nasal sinuses inverted papilloma in the experimental group ,14 had single HPV infection ,4 had single EBV infec-tion ,and 8 had mixed HPV and EBV infection .Of the 10 patients with papilloma malignancy ,5 had single HPV infection ,4 had single EBV infection ,and 1 had mixed HPV and EBV infection .The incidence rate of HPV infec-tion was 64 .7% in the patients with recurrence ,65 .2% in the patients without recurrence ;the incidence rate of EBV infection was 47 .1% in the patients with recurrence ,8 .7% in the patients without recurrence ;while there was significant difference in the incidence rate of EBV infection between the patients with recurrence and the patients without recurrence (P< 0 .05) .CONCLUSION The EBV and HPV infections are prevalent in the

  7. The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.

    Science.gov (United States)

    Lee, Jong Soo; Kim, Young Hi; Park, Young Min

    2015-12-01

    This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

  8. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells.

    Science.gov (United States)

    Akhtar, Reyhan; Ali, Mohd; Mahmood, Safrunnisa; Sanyal, Sankar Nath

    2014-02-01

    Antecedentes: Silibinina un flavonoide a partir de la leche de cardo mariano (Silybum marianum) exhiben una variedad de acciones farmacológicas, incluyendo actividades anti-proliferativos y apoptóticos contra varios tipos de cánceres en animales intactos y líneas celulares de cáncer. En el presente estudio, se estudió el efecto de silibinina en células humanas de cáncer de colon HT-29. Método: Las incubaciones de las células con diferentes concentraciones silibinin (0,783-1.600 ug/ml) para 24, 48 o 72 horas mostró un descenso progresivo de la viabilidad celular. Resultados: La pérdida de la viabilidad celular fue de tiempo de inhibición dependiente y óptima de crecimiento de las células (78%) se observó a las 72 horas. Bajo microscopio invertido, las células muertas fueron vistos como los agregados de células. IC50 (concentración de silibinina matar a las células 50%) los valores fueron 180, 110 y 40 ug/ml a las 24, 48 y 72 horas, respectivamente. Conclusión: Estos resultados volver a hacer cumplir la potenciales contra el cáncer de silibinina, como se informó anteriormente para varias otras líneas celulares de cáncer (Ramasamy y Agarwal (2008), Cancer Letters, 269: 352-62).

  9. Bivariate analysis of basal serum anti-Mullerian hormone measurements and human blastocyst development after IVF

    LENUS (Irish Health Repository)

    Sills, E Scott

    2011-12-02

    Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+\\/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+\\/- SD) terminal serum estradiol during IVF was 5929 +\\/- 4056 pmol\\/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol\\/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.

  10. Increasing trends of herpes zoster in Australia.

    Directory of Open Access Journals (Sweden)

    Raina MacIntyre

    Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

  11. Herpes simplex virus virion host shutoff function.

    Science.gov (United States)

    Kwong, A D; Kruper, J A; Frenkel, N

    1988-03-01

    Herpes simplex virus (HSV) virions contain one or more functions which mediate the shutoff of host protein synthesis and the degradation of host mRNA. HSV type 1 (HSV-1) mutants deficient in the virion shutoff of host protein synthesis (vhs mutants) were isolated and were found to be defective in their ability to degrade host mRNA. Furthermore, it was found that viral mRNAs in cells infected with the vhs 1 mutant have a significantly longer functional half-life than viral mRNAs in wild-type virus-infected cells. In the present study we have mapped the vhs1 mutation affecting the virion shutoff of host protein synthesis to a 265-base-pair NruI-XmaIII fragment spanning map coordinates 0.604 to 0.606 of the HSV-1 genome. The mutation(s) affecting the functional half-lives of host mRNA as well as the alpha (immediate-early), beta (early), and gamma (late) viral mRNAs were also mapped within this 265-base-pair fragment. Thus, the shutoff of host protein synthesis is most likely mediated by the same function which decreases the half-life of viral mRNA. The shorter half-life of infected-cell mRNAs may allow a more rapid modulation of viral gene expression in response to changes in the transcription of viral genes. Interestingly, the vhs1 mutation of HSV-1 maps within a region which overlaps the Bg/II-N sequences of HSV-2 DNA shown previously to transform cells in culture. The possible relationship between the transformation and host shutoff functions are discussed.

  12. Latent Herpes Viral Reactivation in Astronauts

    Science.gov (United States)

    Pierson, D. L.; Mehta, S. K.; Stowe, R.

    2008-01-01

    Latent viruses are ubiquitous and reactivate during stressful periods with and without symptoms. Latent herpes virus reactivation is used as a tool to predict changes in the immune status in astronauts and to evaluate associated health risks. Methods: Viral DNA was detected by real time polymerase chain reaction in saliva and urine from astronauts before, during and after short and long-duration space flights. Results and Discussion: EpsteinBarr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivated, and viral DNA was shed in saliva (EBV and VZV) or urine (CMV). EBV levels in saliva during flight were 10fold higher than baseline levels. Elevations in EBV specific CD8+ T-cells, viral antibody titers, and specific cytokines were consistent with viral reactivation. Intracellular levels of cytokines were reduced in EBVspecific Tcells. CMV, rarely present in urine of healthy individuals, was shed in urine of 27% of astronauts during all phases of spaceflight. VZV, not found in saliva of asymptomatic individuals, was found in saliva of 50% of astronauts during spaceflight and 35 days after flight. VZV recovered from astronaut saliva was found to be live, infectious virus. DNA sequencing demonstrated that the VZV recovered from astronauts was from the common European strain of VZV. Elevation of stress hormones accompanied viral reactivation indicating involvement of the hypothalmic-pituitary-adrenal and sympathetic adrenal-medullary axes in the mechanism of viral reactivation in astronauts. A study of 53 shingles patients found that all shingles patients shed VZV DNA in their saliva and the VZV levels correlated with the severity of the disease. Lower VZV levels in shingles patients were similar to those observed in astronauts. We proposed a rapid, simple, and cost-effective assay to detect VZV in saliva of patients with suspected shingles. Early detection of VZV infection allows early medical intervention.

  13. Cytomegalovirus seropositivity is associated with herpes zoster.

    Science.gov (United States)

    Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

    2015-01-01

    Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

  14. Herpes Simplex Virus Infection Mimicking Bullous Disease in an Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Anne L.Y. Lecluse

    2010-06-01

    Full Text Available Immunodeficient patients are at risk of developing extended or atypical herpes simplex virus infections, which can be easily misdiagnosed. We present the case of a 79-year-old, treatment-induced (oral corticosteroid, immunocompromised female with an extensive atypical herpes simplex virus infection. This patient presented with multiple erosions and vesicles on the trunk with a subacute onset. The clinical differential diagnosis was herpes simplex infection, herpes zoster infection, pemphigus vulgaris or bullous pemphigoid. Due to the atypical clinical presentation and negative Tzanck test, suspicion of viral infection was low. High-dose steroid treatment was initiated. Subsequent histopathology, however, showed a herpes simplex virus infection. After discontinuing steroid treatment and initiating antiviral treatment, the patient recovered within a week. Emphasis must be placed on the importance of clinical awareness of extended and clinically atypical herpes simplex infections in immunocompromised patients. A negative Tzanck test does not rule out the possibility of a herpes infection.

  15. Inhibition of herpes simplex type 1 and type 2 infections by Oximacro(®), a cranberry extract with a high content of A-type proanthocyanidins (PACs-A).

    Science.gov (United States)

    Terlizzi, Maria Elena; Occhipinti, Andrea; Luganini, Anna; Maffei, Massimo E; Gribaudo, Giorgio

    2016-08-01

    In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro(®) and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro(®) prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro(®) and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro(®) completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro(®). Taken together, these findings indicate Oximacro(®) as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections. PMID:27321663

  16. Effect of combinations of antiviral drugs on herpes simplex encephalitis

    Directory of Open Access Journals (Sweden)

    Bryan M Gebhardt

    2009-12-01

    Full Text Available Bryan M Gebhardt1, Federico Focher2, Richard Eberle3, Andrzej Manikowski4, George E Wright41LSU Eye Center, Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; 2Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia, Italy; 3Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA; 4GLSynthesis Inc., Worcester, MA, USAAbstract: 2-Phenylamino-6-oxo-9-(4-hydroxybutylpurine (HBPG is a thymidine kinase inhibitor that prevents encephalitic death in mice caused by herpes simplex virus (HSV types 1 and 2, although its potency is somewhat less than that of acyclovir (ACV. The present study was undertaken to determine the effect of combinations of HBPG and either ACV, phosphonoformate (PFA, or cidofovir (CDF against HSV encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and treated twice daily intraperitoneally for five days with HBPG, alone or in combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days, and the day of death of each was recorded. All of the combinations showed additivity, and the combination of HBPG + ACV appeared to be synergistic, ie, protected more mice against HSV-1 encephalitis compared with each drug given alone. Delay of treatment with HBPG for up to two days was still effective in preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor HBPG and the antiherpes drug ACV may have synergistic activity against HSV encephalitis. The development of a potent and safe combination therapy for the prevention and/or treatment of HSV infection of the central nervous system can improve the outcome of this infection in humans.Keywords: antivirals, herpetic encephalitis

  17. Performance enhancement, elite athletes and anti doping governance: comparing human guinea pigs in pharmaceutical research and professional sports.

    Science.gov (United States)

    Camporesi, Silvia; McNamee, Michael J

    2014-02-05

    In light of the World Anti Doping Agency's 2013 Code Revision process, we critically explore the applicability of two of three criteria used to determine whether a method or substance should be considered for their Prohibited List, namely its (potential) performance enhancing effects and its (potential) risk to the health of the athlete. To do so, we compare two communities of human guinea pigs: (i) individuals who make a living out of serial participation in Phase 1 pharmacology trials; and (ii) elite athletes who engage in what is effectively 'unregulated clinical research' by using untested prohibited or non-prohibited performance enhancing substances and methods, alone or in combination. Our comparison sheds light on norms of research ethics that these practices exacerbate with respect to the concepts of multiplicity, visibility, and consistency. We argue for the need to establish a proper governance framework to increase the accountability of these unregulated research practices in order to protect the human guinea pigs in elite sports contexts, and to establish reasonable grounds for the performance enhancing effects, and the risks to the health of the athlete, of the methods and substances that might justify their inclusion on the Prohibited List.

  18. Performance enhancement, elite athletes and anti doping governance: comparing human guinea pigs in pharmaceutical research and professional sports.

    Science.gov (United States)

    Camporesi, Silvia; McNamee, Michael J

    2014-01-01

    In light of the World Anti Doping Agency's 2013 Code Revision process, we critically explore the applicability of two of three criteria used to determine whether a method or substance should be considered for their Prohibited List, namely its (potential) performance enhancing effects and its (potential) risk to the health of the athlete. To do so, we compare two communities of human guinea pigs: (i) individuals who make a living out of serial participation in Phase 1 pharmacology trials; and (ii) elite athletes who engage in what is effectively 'unregulated clinical research' by using untested prohibited or non-prohibited performance enhancing substances and methods, alone or in combination. Our comparison sheds light on norms of research ethics that these practices exacerbate with respect to the concepts of multiplicity, visibility, and consistency. We argue for the need to establish a proper governance framework to increase the accountability of these unregulated research practices in order to protect the human guinea pigs in elite sports contexts, and to establish reasonable grounds for the performance enhancing effects, and the risks to the health of the athlete, of the methods and substances that might justify their inclusion on the Prohibited List. PMID:24499536

  19. Bioactivity assays and application of 125I labeled human mouse chimeric anti-CD22 monoclonal antibody SM03

    International Nuclear Information System (INIS)

    To investigate the bioactivity and application of 125I labeled human mouse chimeric monoclonal SM03, SM03 was labeled with 125I using Indogen method. The labeled mixture was purified by Sephacryl S-300 HR separation chromospectry. The purity and concentration of separated fractions were determined by HPLC and Protein Assay Kit, respectively. Competitive binding method and ELISA method were used for bioactivity assays. 125I-SM03 was applied to screen cell lines which express the most abundant CD22 antigen. The purity and recovery of 125I-SM03 were >99% and >47%, respectively. The bioactivity of 125I- SM03 and SM03 hasn't significant difference in statistics. Ramos cell line had the strongest special radioactivity when 125I-SM03 bound with in Raji, Daudi and Ramos cell lines. Indogen method is a good way to label Human mouse chimeric anti-CD22 monoclonal antibody SM03 and the label will not affect the activity of SM03. The 125I-SM03 not only can be used for detect agent, but also may be put into market for NHL therapy. (authors)

  20. Berberine Inhibited Radioresistant Effects and Enhanced Anti-Tumor Effects in the Irradiated-Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    The purpose of this study was to elucidate the mechanism underlying enhanced radiosensitivity to 60Co γ-irradiation in human prostate PC-3 cells pretreated with berberine. The cytotoxic effect of the combination of berberine and irradiation was superior to that of berberine or irradiation alone. Cell death and Apoptosis increased significantly with the combination of berberine and irradiation. Additionally, ROS generation was elevated by berberine with or without irradiation. The antioxidant NAC inhibited berberine and radiation-induced cell death. Bax, caspase-3, p53, p38, and JNK activation increased, but activation of Bcl-2, ERK, and HO-1 decreased with berberine treatment with or without irradiation. Berberine inhibited the anti-apoptotic signal pathway involving the activation of the HO-1/NF-κB-mediated survival pathway, which prevents radiation-induced cell death. Our data demonstrate that berberine inhibited the radioresistant effects and enhanced the radiosensitivity effects in human prostate cancer cells via the MAPK/caspase-3 and ROS pathways